1

Curriculum Vitae

Chiara Cirelli, MD, PhD

University of Wisconsin - Madison

School of Medicine

Department of Psychiatry

RESEARCH STATEMENT

Long-term research goal of the laboratory and overall accomplishments

My research aims at understanding the function of sleep and clarifying the functional

consequences of sleep loss. I believe that the key to understanding sleep is to be found at the

intersection between the cellular and the system’s level. This is why my laboratory uses a

combination of different approaches, from genetics in fruit flies to whole-genome expression

profiling and ultrastructural studies in invertebrates and mammals, to behavioral, biochemical, and

electrophysiological analysis in rodents and humans.

Lines of work

1. Fly genetics. Identification of genes involved in sleep regulation using forward genetics in

Drosophila. We and others have demonstrated in 2000 that fruit flies sleep and need sleep in much

the same way as mammals do (Shaw et al., Nature 2000; Hendricks et al., Neuron 2000; Huber et

al., Sleep 2004; Cirelli et al., Nature 2005). This finding has opened the way to the genetic

dissection of sleep using mutant screening and other powerful tools of genetic manipulation that are

available in Drosophila. Over the past 15 years my laboratory has performed large-scale

mutagenesis screening for sleep phenotypes in Drosophila, which resulted in the identification of

the first extreme short sleeper mutant (Cirelli et al., Nature 2005). This study demonstrated that a

point mutation in the voltage-sensing module of the voltage-dependent potassium channel Shaker

abolishes the Shaker current and decreases sleep from 900 to 300min/day. Thus, Shaker appears to

be a key regulator of sleep amount in fruit flies. Importantly, Shaker-like channels are also present

in mammals, and in a follow-up study we found that knockout mice lacking a Shaker homologue

also have reduced sleep (Douglas et al., BMC Neuroscience 2007). While characterizing other

mutations that modify daily sleep amounts we found that several of them affect genes involved in

synaptic plasticity, including the Drosophila homologue of the gene coding for the fragile X metal

retardation protein (Bushey et al., J Neuroscience 2009). Recently, using in vivo calcium imaging

my we have been able to record the activity of many neurons in the fly brain across the sleep/wake

cycle and after sleep deprivation (Bushey et al., PNAS 2015). We found that like in mammals,

Drosophila neurons are more active and respond more to stimuli when the fly is awake than when is

asleep. Moreover, we found that as in rodents and humans, after long sleep deprivation some

neurons seem to go “offline”, as usually only do during sleep, even is the fly is moving and the rest

of the brain is awake. This phenomenon of “local sleep” in an awake brain is probably very relevant

to explain the cognitive impairment after sleep deprivation. Overall, the studies in Drosophila show

that sleep need is strongly related to experience-dependent plasticity during wake, an idea that we

are actively testing in several animal models, and with different approaches (see below).

2. Transcriptomics, proteomics, microdialysis and voltammetry. Molecular and

neurochemical correlates of sleep, wake, and sleep deprivation. My laboratory has pioneered the

2

use of whole-genome profiling to identify the genes whose expression changes in the brain in sleep

relative to wakefulness. Since 1998 we have pursued such genome-wide screening using high-

density DNA microarrays in fruit flies, rats, hamsters and humans. In rats, for instance, we have

found that hundreds of genes are differentially expressed in the brain during sleep and waking

(Cirelli et al., Neuron 2004). These genes belong to diverse and often complementary functional

categories, suggesting that sleep and wakefulness favor different cellular processes. Wake-related

transcripts are involved in energy metabolism, excitatory neurotransmission, transcriptional

activation, synaptic potentiation and memory acquisition, and the response to cellular stress. Sleep-

related transcripts are involved in brain protein synthesis, synaptic depression, as well as membrane

trafficking and maintenance, including cholesterol metabolism, myelin formation, and synaptic

vesicle turnover. Recently we also used the translating ribosome affinity purification technology

combined with microarray analysis to obtain a genome-wide profiling of oligodendrocytes and

astrocytes (Bellesi et al., J Neuroscience 2013). We found that hundreds of transcripts in glial cells

are differentially expressed due to behavioral state and sleep loss. Moreover, we found that

sleep/wake affect the proliferation of oligodendrocyte precursors cells, as well as the movement of

astrocytic processes contacting synapses. Finally, we found that a key factor that controls the

modulation of gene expression by behavioral state is the activity of the noradrenergic system of the

locus coerulues (LC), which is high during wake and low during sleep (Cirelli et al., Science 1996; J

Neuroscience 2000, 2004). High noradrenaline (NA) levels during wake are required for the

induction of transcripts involved in synaptic plasticity and in the cellular response to stress. By

contrast, low NA levels during sleep are associated with the increased expression of transcripts

favoring protein synthesis. In a recent study in collaboration with Prof. Pier Andrea Serra of the

University of Sassari, we used in vivo microdialysis in mice to determine for the first time how NA

levels change in prefrontal (mPFC) and motor (M1) cortex during the physiological sleep/wake

cycle and in the course of sleep deprivation. We found that absolute NA levels are higher in mPFC

than in M1, and in both areas decline during sleep and increase during wake. Crucially, we also

found that by the end of sleep deprivation NA levels decline in mPFC but remain high in M1,

suggesting that during prolonged wake LC neurons projecting to prefrontal cortex may fatigue more

markedly, or earlier, than other LC cells. This finding may help explaining the significant cognitive

impairment associated with sleep deprivation. We are planning follow-up studies in collaboration

with Prof. Serra and his laboratory, using microdialysis and fast-scan cyclic voltammetry, to identify

other metabolites affected by sleep loss in cortex and subcortical areas.

3. The synaptic homeostasis hypothesis. The results of these and other studies have prompted a

new hypothesis about the functions of sleep. Specifically, my long-time collaborator, Dr. Giulio

Tononi, and I have hypothesized that the amount of synaptic potentiation that occurs during wake is

a major determinant of sleep intensity, and that sleep is needed to down-regulate synaptic weight.

The synaptic homeostasis hypothesis (Tononi and Cirelli Brain Res Bull 2003, Sleep Medicine

Review 2006; Neuron 2014) is being tested at several different levels in a joint effort. Dr. Tononi’s

team uses computer simulations and performs human experiments with high-density EEG and

transcranial magnetic stimulation. My team uses flies, mice and rats to test the hypothesis at a

molecular, behavioral, electrophysiological, and ultrastructural level. We confirmed in several

studies in adult flies, rats and humans that learning, enriched experience, and the occurrence of

synaptic potentiation during waking increase sleep need and sleep intensity (Huber et al., Sleep

3

2004; Huber et al., Sleep 2007; Faraguna et al., J Neuroscience 2008; Hanlon et al., Sleep 2009).

We also found that in adult flies, protein levels of key components of central synapses, as well as

synapse number, are high after wake and low after sleep in all major areas of the Drosophila brain

(Gilestro et al., Science 2009; Bushey et al., Science 2011). Similarly, in adult rats, molecular and/or

electrophysiological markers of synaptic strength are high after wakefulness and low after sleep in

cortex and hippocampus (Vyazovskiy et al., Nature Neuroscience 2008). Moreover, in adolescent

mice, sleep favors spine pruning, while wake favors spine growth (Maret et al., Nature

Neuroscience 2011). Overall, these data suggest that wake is associated with net synaptic

potentiation, whereas sleep may favor global synaptic depression, thereby helping to preserve an

overall balance of synaptic strength. Our current experiments in transgenic flies and mice use

confocal and repeated in vivo two-photon microscopy, as well as serial block phase scanning

electron microscopy, to confirm that an essential function of sleep is to promote a homeostatic

reduction in synaptic strength. We are also testing whether lack of sleep, especially during

adolescence, may have long-term consequences for the functional and anatomical connectivity of

the brain.

4

BACKGROUND INFORMATION

Name: Chiara Cirelli

Address: Department of Psychiatry

University of Wisconsin/Madison

6001 Research Park Blvd

Madison, WI 53719

U.S.A.

Tel. 608-263 9236

Fax 608-265 2953

ccirelli@wisc.edu

Education:

Degrees

10/1984-11/1990 M.D., Magna cum laude

Scuola Superiore S.Anna and University of Pisa, Italy

Dissertation: Meccanismi neurochimici di regolazione del sonno

desincronizzato: ruolo dei recettori alpha2-noradrenergici (published)

12/1990-11/1993 Ph.D. in Neuroscience, Scuola Superiore S.Anna and University of

Pisa, Italy

Dissertation: Meccanismi noradrenergici di regolazione del sonno

REM (published)

Certifications

1990 Certification in General Medicine, University of Pisa, Italy

Positions Held:

1994-1997 Junior Fellow in Experimental Neuroscience, The Neurosciences

Institute, San Diego, California

1998-2001 Associate Fellow in Experimental Neuroscience, The Neurosciences

Institute, San Diego (equivalent to Assistant Professor)

2001- June 2006 Assistant Professor, Department of Psychiatry, University of

Wisconsin, Madison

July 2006–April 2012 Associate Professor, Department of Psychiatry, University of

Wisconsin, Madison

May 2012 Professor, Department of Psychiatry, University of Wisconsin,

Madison

5

Honors and Awards:

1984 Bachelor Degree cum laude, Ferrara, Italy

1984-1990 Winner of national competition (2 positions/year) for M.D.

fellowship at the Scuola Superiore S.Anna, Pisa

1990 M.D. with Honors

1990-1993 Winner of national competition (2 positions/year) for Ph.D.

fellowship at the Scuola Superiore S.Anna, Pisa

1993 Ph.D. with Honors

1993-1994 Recipient, Post-doctoral fellowship, Italian Space Agency, Rome,

Italy

1994 Winner of international competition (4 positions/year) for fellowship

in Experimental Neuroscience at The Neurosciences Institute, San

Diego

2000 Recipient, Brain Research Interactive Young Investigator Award for

the paper published in Brain Research entitled “Gene expression in

the brain across the sleep-waking cycle” Brain Research 885: 303-

321, 2000

2005 Magisterial lecture, Sleep Research Society, APSS Meeting, Denver,

Colorado

2005 Special lecture, Society for Neuroscience, Annual Meeting

Washington D.C.

2012 Speaker, Kavli Prize Symposium on Neuroscience, Bergen, Norway.

2012 Closing lecture, European Sleep Research Society, Biannual Meeting

Paris, France.

Society Memberships and Editorial Boards:

1992 - : Societa' Italiana di Fisiologia

1994 - : European Sleep Research Society

1994 - : European Neuroscience Association

1996 - : Society for Neuroscience

1996 - : American Sleep Research Society

2000 - : American Academy of Sleep Medicine

2003 - : Editorial Advisory Board, Journal of Sleep Research

2003 - : Editorial Board, Sleep

6

TEACHING ACTIVITIES

CLASSROOM TEACHING

Medical School

1991-1993 University of Pisa, Italy; class demonstrations of

electroencephalographic techniques and of diagnostic procedures.

Total of 10 hrs demonstrations / year.

Post-Graduate Training for the Sleep Research Society

10/02/98-10/08/98 Annual Summer Sleep Workshop, National Multi-site Training

Program for Basic Sleep Research. “Molecular and cellular

foundations of sleep disorders”, Lake Arrowhead, California.

Approximately 50 hrs, 20-30 students. Served as Faculty member.

09/12/00-09/17/00 Annual Summer Sleep Workshop, National Multi-site Training

Program for Basic Sleep Research. “The basics of sleep behavior”

Lake Arrowhead, California. Approximately 50 hrs, 20-30 students.

Served as Faculty member.

2000-2001 National Multi-site Training Program for Basic Sleep Research.

Served as principal mentor for Dr. Rene Salazar, Ph.D., recipient of a

post-doctoral fellowship from the Multi-site Training Program of the

Sleep Research Society. Dr. Salazar’s project was entitled “Analysis

of protein expression during sleep”.

Undergraduate Training at UW

Oct 2002 Neuroscience 675 (Coordinator Dr. Tom Yin): Undergraduate

Neurobiology Seminar Series. One hour lecture on “The mystery of

sleep”.

Nov 2002 “The mistery of sleep and the fruit fly”, lecture to undergraduates,

non-biology major (host Prof. Jose Quintans), University of Chicago

Oct 2003 Neurobiology 500 (Coordinator Dr. Peter Lipton). One hour lecture

on “Fly sleep”.

Oct 2005 Neuroscience 500 (Coordinator Dr. Peter Lipton). One hour lecture

on “Molecular and genetic approaches to study sleep”.

Oct 2007, 2009 Neuroscience 500 (Coordinator Dr. Peter Lipton). One hour lecture

on “Sleep deprivation”.

Graduate Training at UW - Neuroscience Training Program (NTP)

7

Nov 2001 Psychology/Zoology 695, graduate course on the “Biology of Mind”.

One hour lecture on the effects of sleep deprivation.

Jan-Feb 2003 Organizer and discussion leader together with Dr. Ruth Benca of a

subgroup on “Current perspectives on the functions of sleep”. The

subgroups are one of the main training activities within the NTP. In

each subgroup, ~ 10 students meet regularly with one or 2 faculty

members during a 6-8 week period to discuss a topic in neuroscience.

At the end of the subgroup students present the results of their review

of the topic in the Monday night Neuroscience seminars, which take

place weekly and involves all the NTP faculty and students. Total of

25 hours of lectures/discussions.

Apr 2005 Medical Genetics/Oncology 707. Lecture followed by roundtable

dialog with first and second year doctoral students in Genetics.

Apr 2006 Respiratory Neurobiology Training Program (Project Director: Dr.

Gordon Mitchell). One hour lecture on the molecular biology and

genetics of sleep.

Jan-April 2007 Basic sleep mechanisms and sleep disorders / NTP675 (Course

Director Dr. Ruth Benca) 4 lectures (1.5 hr each) on anatomy of

sleep, sleep deprivation, and genetics of sleep.

Jan-April 2008 Basic sleep mechanisms and sleep disorders / NTP675 (Course

Director Dr. Ruth Benca) 6 lectures (1.5 hr each) on anatomy of

sleep, sleep deprivation, and genetics of sleep.

Sept-Dec 2008 Basic sleep mechanisms and sleep disorders / NTP675 (Course

Director) 20 lectures (1.5 hr each) on anatomy, physiology,

pharmacology and genetics of sleep.

Jan-May 2010 Basic sleep mechanisms and sleep disorders / NTP675 (Course Co-

Director) 20 lectures (1.5 hr each) on anatomy, physiology,

pharmacology and genetics of sleep.

Mar-April 2011 Organizer and discussion leader of a subgroup on “Model organisms

in sleep research”. Total of 25 hrs of lectures/discussions. (students’

evaluations provided)

Oct 2011 Entomology 201 "Insects and Human Culture", (Chair Dr. David

Hogg); guest lecturer on "Sleep, flies and synaptic plasticity". UW

Dept. of Entomology, UW Madison.

Nov-Dec 2011 Department of Statistics, masters (MS) exam Fall 2011. Provided

data and analysis questions for the exam using our ongoing

microarray experiments. Twelve students taking the MS exam

analyzed the array data and wrote a report to answer the scientific

questions (letter from Prof. Cecile Ane, Dept of Statistics, included).

Sept-Dec 2011 Basic sleep mechanisms and sleep disorders / NTP675 (Course Co-

Director with Dr. Tim Juergens) 20 lectures (1.5 hr each) on

anatomy, physiology, pharmacology and genetics of sleep. (students’

evaluations are not collected by the NTP for this course)

Sept-Dec 2012 Basic sleep mechanisms and sleep disorders / NTP675 (Course Co-

Director with Dr. Tim Juergens) 8 lectures (1.5 hr each) on anatomy,

physiology, pharmacology and genetics of sleep.

8

Sept-Dec 2014 Basic sleep mechanisms and sleep disorders / NTP675 (Course Co-

Director with Dr. Ruth Benca) 15 lectures (1.5 hr each) on anatomy,

physiology, pharmacology and genetics of sleep.

Other Training outside UW Madison

2001-2013 “Sleep: Neurobiology, Medicine, and Society”, Graduate and

undergraduate course, University of Michigan, Ann Arbor. One hour

lecture on “Genetics of Sleep” every year. Approximately 100-200

students every year attend the lecture.

June 2002 Teaching course on “Molecular methods in sleep research:

microarrays, quantitative trait loci and mutagenesis.” 4 hours, during

the 16th

Meeting of the European Sleep Research Society, Reykjavik,

Iceland. Approximately 40 students attended the course.

Feb 2005, 07 A Primer of Sleep Research, organized by the American Sleep

Research Society. A two and a half day interactive course to

understand major topics and techniques used in sleep research. Two-

hour lecture on genetics of sleep. Approximately 30 participants,

including students, sleep researchers, industry representatives.

Since appointment as associate professor with tenure track:

Feb 2007 Advanced Sleep Medicine Course. A two and a half day interactive

course to discuss state-of-the-art research in sleep. One-hour lecture

on molecular biology of sleep. Approximately 200 participants,

including students, sleep researchers, industry representatives.

June 2009 Annual Trainees Symposium Series held in conjunction with the

Annual Sleep Meeting (300 trainees). One-hour workshop on

genetics in sleep research. (students’ evaluations provided)

June 2011 A Primer of Sleep Research, organized by the American Sleep

Research Society. A one-day interactive course to understand major

topics and techniques used in sleep research. One-hour lecture on

genetics of sleep. (students’ evaluations provided)

MENTORING

Research Apprentice Program, UW Madison

Summer 2002 Mentor for high school student Chetasi Talati. Chetasi learned to

analyze fly sleep and conducted a project involving the analysis of

the effects of cAMP on sleep and waking in wild-type flies. After she

concluded the Research Apprentice Program, she has continued to

work in my laboratory for 2 years.

Summer 2003 Mentor for high school student Roman Aykido. Roman learned to

analyze fly sleep and conducted a project to characterize a short

sleeper mutant identified in the laboratory. After she concluded the

9

Research Apprentice Program, she has continued to work in my

laboratory for 2 years.

Summer 2004 Mentor for high school student Tenzin Woeser. Tenzin learned to

analyze fly sleep and conducted a project to characterize a fly mutant

resistant to the effect of sleep deprivation.

Summer 2008 Mentor for high school student Katie Scheuer. Katie learned to

analyze fly sleep and conducted a project to measure how the

expression of synaptic markers in the fly brain changes between

sleep and waking.

Summer 2010 Mentor for high school student Sadhana Murali, who participated in

the project “The effects of meditation on spontaneous brain and

slow-wave activity during sleep”.

Medical Scholars Program (MSP) Summer Clinical Fellowship Program, UW

Madison

Summer 2001 Mentor for student Jennifer Lamps. Jennifer was responsible for the

maintenance of fly stocks and the analysis of fly sleep. She has

started Medical School in September 2001.

Undergraduate Research Scholars Program, UW Madison

April-June 2003 Mentor of Korey Wylie, a student in the Biology 152 course; 120

hours of research; Korey completed a project entitled “Mutagenesis

screening to identify phenotypes with resistance to sleep.” Korey

continued to work in my lab until August 2005, when he started

Medical School in Denver, Colorado. In 2004, Korey was awarded a

Hilldale and Holstrom Undergraduate Fellowships and completed

under my mentorship a project entitled “Role of juvenile hormone in

the regulation of Drosophila sleep”.

January-April 2006 Mentor of Keren Weltman, a student in the current Biology 152

course. Keren spent 120 hours of research in my laboratory. She was

involved in a project entitled “Role of voltage-dependent portassium

channels in sleep regulation in rats.”

Neurosci 990 class and Psychiat 699 class (Independent, Directed Study in Research); 1-2

students / semester (each student spent 60/120 hrs / semester in the lab)

Spring 2007 DeNucci, Daniel Joseph (fly sleep and fundamentals of mutagenesis

screening)

Spring 2008 Hines, Paul James (synaptic plasticity and sleep in rats)

Fall 2008 Lee, Christopher George Alsager (potassium channels and fly

sleep)

Spring, Fall 2008 Uy, Marlene (characterization of fly sleep mutants)

Fall 2009 Choi, Byul (fly sleep and fundamentals of mutagenesis screening)

Spring 2010 Potters, Mark Anthony (effects of sleep loss on neuronal

morphology in flies)

Fall 2010 Lee, Christopher George Alsager (sleep deprivation in mice)

10

Fall 2011 Zoltan, Jeffrey Thomas (effects of sleep deprivation on olfactory

learning in mice)

Fall 2011 Jones, Benjamin (in vivo calcium imaging in mice)

Fall 2011/

Spring 2012 Severson, Kyle (synaptic changes after sleep deprivation in flies)

Fall 2012/

Spring 2013 Jones, Benjamin (effects of sleep loss in adolescent mice)

Fall 2012/ Marki, Klapperich (effects of sleep loss in adolescent mice)

Spring 2013

Fall 2013, 2014 Andrea Schroeder (sleep/wake ultrastructural effects)

Graduate students, Neuroscience Training Program, M.D. Ph.D. Training Program

Member of the Thesis Committee:

2002-2008 Hanlon, Erin (sleep deprivation and appetitive behaviors)

2003-2008 Alsene, Karen (prepulse inhibition, animal models of schizophrenia)

2003-2008 Esser, Steve (transcranial magnetic stimulation and sleep)

2003-2008 Newman, Sarah (comparative aspects of sleep in birds and

mammals)

2004-2009 Gerstner, Jason (sleep and circadian rhythms)

2005-2009 Jones, Stephany (molecular aspects of sleep in sparrows; co-mentor)

2006-2010 Murphy, Michael (source analysis of sleep slow waves)

2007-2011 Guenther, Courtney (atypical PKC and respiratory motor control)

2006-2011 Qi, Chao (models of rodent behavioral inhibition)

2006-2011 Riedner, Brady (analysis of sleep slow waves)

2007-2011 Landsness, Eric (sleep and learning)

2012- Funk, Chadd (sleep and consciousness)

Major Professor, NTP students:

2007-2011 Dash, Michael (brain metabolism and sleep)

2009-2013 Nelson, Aaron (sleep and functional connectivity in young mice)

2012- Rodriguez, Alexander (mechanisms underlying sleep need)

.

Undergraduate and Graduate students, outside UW

Aug 2005-present Supervision of Dr. Ugo Faraguna, M.D., Ph.D. student at the Scuola

Superiore S.Anna and University of Pisa, Italy. He has obtained an

independent position as Assistant Professor in Pisa, Italy (starting in

2012)

Jan-Dec 2009 Supervision of Susan Leemburg, PhD student in Dr. Claudio

Bassetti's laboratory at the University of Zurich, Switzerland

11

Jun 2011-May 2012 Supervision of Albrecht Vorster, undergraduate neurobiology student

from the University in Freiburg, Germany

Mar 2012-Jan 2013 Supervision of Juliana Noguti, M.D. Ph.D. student from Paulista

Medical School, Federal University of São Paulo, Brazil

Post-doctoral students

Mentor of postdoctoral students:

2004-2007 Dr. Reto Huber (Ph.D. in Neuroscience at the University of Zurich,

Switzerland); after a 4-year stay in the lab, Dr. Huber returned to

Switzerland in 2007 to accept a position of Assistant Professor at the

Department of Pharmacology, University of Zurich

2004-present Dr. Daniel Bushey (Ph.D. in Genetics at the University of Alberta,

Canada) joined the laboratory in 2004 to learn how to apply genetic

approaches to neuroscience); he is currently an associate scientist at

UW-Madison, Dept of Psychiatry

2005-2011 Dr. Vladislav Vyazovskiy (Ph.D. in Neuroscience at the University

of Zurich, Switzerland), joined the lab in the summer of 2005 to

learn how to apply molecular techniques to the study of sleep in

rodents). He has obtained an independent position as Assistant

Professor at the University of Surrey, U.K. (starting in Feb 2012)

2006-2009 Dr. Giorgio Gilestro (Ph.D. in Molecular Biology at the Institute of

Molecular Biotechnology of the University of Vienna, Austria)

joined the lab in September 2006 to study fly sleep. He is currently a

Junior Research Fellow at the Imperial College in London, U.K

2008-2010 Dr. Stephanie Maret (Ph.D. in Biology at the Center for Integrative

Genomics, University of Lausanne, Lausanne, Switzerland) joined

the lab in May 2008 to study in mice the effects of sleep on synaptic

plasticity during development. She returned to Switzerland to pursue

a second post-doctoral training in 2010

2011-2012 Dr. Marie-Eve Tremblay (Ph.D. in Neuroscience at the University of

Montreal, Canada) joined the lab in April 2011 to study

ultrastructural effects of sleep and sleep loss in the adolescent and

adult brain. She obtained an independent position at the U of Quebec

in 2012.

2011- Dr. Luisa DeVivo (Ph.D. in Neuroscience at the University of

Ancona, Italy) joined the lab in April 2011 to study ultrastructural

effects of sleep and sleep loss in the adolescent and adult brain

2014- Dr. Sakiko Honjoh (Ph.D. from the U. of Kyoto, Japan) joined the

lab in 2012 to study cortical and thalamic control of sleep and

consciousness.

2014- Dr. Hirotaka Nagai (M.D., Ph.D. from the U. of Kyoto, Japan) joined

the lab in 2014 to study ultrastructural effects of sleep and learning in

the adolescent and adult brain.

Tenure track faculty

12

Mentor of Assistant Professors:

Dec 2006-2009 Women faculty mentoring program (Julie Olson, Assistant Professor,

Neurological Surgery)

April 2011-present Mentoring committee, Dept of Psychiatry (Brian A Baldo, Assistant

Professor, Psychiatry)

Sept 2011-present Mentoring committee, Dept of Psychiatry (Ryan Herringa, Assistant

Professor of Child & Adolescent Psychiatry, Psychiatry)

Dec 2011-present Mentoring committee, Dept of Psychiatry (Rasmus Birn, Assistant

Professor, Psychiatry)

Jan 2012-present Mentoring committee, Dept of Psychiatry (Reid Alisch, Assistant

Professor, Psychiatry)

Jan 2014-present Mentoring committee, Dept of Psychiatry (Ryan Herringa, Assistant

Professor, Psychiatry)

INVITED PUBLIC PRESENTATIONS AND GRAND ROUNDS

1. Grand Rounds, 1999, April: “Changes in brain gene expression during the sleep/waking cycle

and after sleep deprivation”, University of California at San Diego, San Diego

2. Guest Lecturer, 2000, October: “Molecular correlates of sleep and waking”, Washington State

University, Dept of Veterinary Medicine, Pullman.

3. Guest Lecturer, 2001, November: “A molecular window on sleep and waking”, UW Dept. of

Preventive Medicine (host Dr. Jerry Dempsey). Respiratory Neurobiology Seminar (Gas Club),

UW Madison.

4. Grand Rounds, 2001, December: “A molecular window on sleep and wakefulness”, University

of Michigan, Dept. of Anesthesiology, Ann Arbor.

5. Guest Lecturer, 2002, March: “Gene expression and sleep”, Sleep Lab Case Conference, UW

Dept. of Medicine, UW Madison.

6. Guest Lecturer, 2002, July: “Genetics and function of sleep in insects”, UW Dept. of Psychiatry;

research seminar for 3rd

year residents, UW Madison.

7. Guest Lecturer, 2002, November: “Sleep in insects”, Zoology Department Colloquium (host Dr.

Yevgenya Grinblat), UW Dept. of Zoology/Anatomy, UW Madison

8. Guest Lecturer, 2002, December: “Sleep lessons from invertebrates”, University of Michigan,

Dept. of Anesthesiology, Ann Arbor.

9. Grand Rounds, 2003, September: "A molecular window on Sleep and wakefulness", UW Dept.

of Psychiatry, UW Madison.

10. Guest Lecturer, 2003, September: "Drosophila sleep", UW Dept. of Entomology (host: Dr.

Susan M. Paskewitz), UW Madison.

11. Guest Lecturer, 2004, October: “Sleep research: from bench to bedside”, keynote presentation

with Drs Ruth Benca and Giulio Tononi, UW Medical School, Summer Research Fall Forum.

12. Grand Rounds, 2005, September: “Sleep: from mechanism to function”, George Mason

University, Fairfax, VA

13

13. Guest Lecturer, 2005, November: "From flies to humans: a molecular window on sleep", John

Rankin Memorial Sleep Symposium, UW Madison

14. Guest Lecturer, 2006, June: "Sleep and genes: molecular and genetic studies", APSS 2006

Course “Basic of Sleep”, Dr. Mary Carskadon, Chair. APSS 2006, Salt Lake City.

15. Guest Lecturer, 2006, June: "Genetics of Sleep", APSS 2006 Course “Year-in-Review”, Dr.

Michael Vitiello, Chair. APSS 2006, Salt Lake City.

16. Guest Lecturer, 2007, March: "Molecular genetics, psychopathology, and sleep disorders"

Psychopathology course, Dr. Heather Abercrombie, Chair. UW Dept. of Psychiatry, UW

Madison.

17. Grand Rounds, 2007, April: “Genetics of sleep disorders”, UW Dept. of Psychiatry, UW

Madison.

18. Guest Lecturer, 2008, March: “Sleep and brain plasticity”, National Sleep Awareness Week

organized by the National Sleep Foundation, Washington DC

19. Guest Lecturer, 2009, April: University Roundtable Series “Sleep on It: The Function of

Sleep and the Consequence of Sleep Loss”. Memorial Union, UW Madison.

20. Guest Lecturer, 2009, November: “Sleep and the brain” Conversations in Science Series, a

part of the Wisconsin Initiative for Science Literacy (WISL.) to connect UW faculty and K-

12 educators in Dane County. Sonderegger Science Center, UW Madison.

21. Guest Lecturer, 2011, October: "Sleep and synaptic plasticity" Entomology 201 class "Insects

and Human Culture", Dr. David Hogg, Chair. UW Dept. of Entomology, UW Madison.

22. Guest Lecturer, 2012, January: “Sleep and synaptic homeostasis”, Stanford Sleep Grand

Rounds, Stanford University, Palo Alto, CA.

23. Speaker, April 2012: “Sleep and synaptic plasticity”, UW Milwaukee, Neuroscience Seminar

Series

24. Speaker, September 2012 “Sleep and synaptic plasticity”, “Kavli Prize Symposium on

Neuroscience, Bergen, Norway.

25. Plenary Speaker, September 2012 “Sleep and synaptic plasticity”, European Sleep Research

Society, Biannual Meeting Paris, France.

PUBLICATIONS

Papers published in refereed journals:

1. Cirelli C (1991) “Meccanismi neurochimici di regolazione del sonno desincronizzato: ruolo dei

recettori alpha2-noradrenergici” Tesi di Laurea in Medicina e Chirurgia, Universita` di Pisa, pp.

73, 1990.

2. Tononi G, Pompeiano M, Cirelli C (1991) Suppression of desynchronized sleep through

microinjection of the a2-adrenergic agonist clonidine in the dorsal pontine tegmentum of the cat.

Pflügers Arch 418:512-518.

3. Tononi G, Pompeiano M, Cirelli C (1991) Effects of local pontine injection of noradrenergic

agents on desynchronized sleep in the cat. Prog Brain Res 85:545-553.

4. Cirelli C, Tononi G, Pompeiano M, Pompeiano O, Gennari A (1992) Modulation of

desynchronized sleep through microinjection of a1-adrenergic agonists and antagonists in the

dorsal pontine tegmentum of the cat. Pflügers Arch, 422:273-279.

14

5. Pompeiano M, Cirelli C, Tononi G (1992) Effects of sleep deprivation on Fos-like

immunoreactivity in the rat brain. Archives italiennes Biologie 130:325-335.

6. Cirelli C, Pompeiano M, Tononi G (1993) Fos-like immunoreactivity in the rat brain in

spontaneous wakefulness and sleep. Archives italiennes Biologie 131:327-330.

7. Cirelli C, Pompeiano M, d’ Ascanio P, Pompeiano O. (1993) Early c-fos expression in the rat

vestibular and olivocerebellar systems after unilateral labyrinthectomy. Archives italiennes de

Biologie 131: 71-74.

8. Cirelli C, d’ Ascanio P, Horn E, Pompeiano O, Stampacchia G (1993) Modulation of

vestibulospinal reflexes through microinjection of an 1-adrenergic antagonist in the dorsal

pontine tegmentum of decerebrate cats. Archives italiennes de Biologie 131: 275-302.

9. Pompeiano M, Cirelli C, Tononi G (1994) Immediate-early genes in spontaneous wakefulness

and sleep: Expression of c-fos and NGFI-A mRNA and protein. J Sleep Res 3:80-96.

10. Tononi G, Cirelli C, Pompeiano M (1994) The locus coerules and immediate early genes in

spontaneous and forced wakefulness. Brain Res Bull 35:589-596.

11. Cirelli C, Pompeiano M, d’Ascanio P, Arrighi P, Pompeiano O (1995) c-Fos expression in the

rat brain after unilateral labyrinthectomy and its relation to the uncompensated and compensated

stages. Neuroscience 70: 515-546.

12. Cirelli C, Pompeiano M, Tononi G (1995) Sleep-waking changes after c-fos antisense injections

in the medial preoptic area. Neuroreport 6:801-805.

13. Cirelli C, Pompeiano M, Arrighi P, Tononi G (1995) Fos-positive cells activated by waking in

the medial preoptic area are not GABAergic. Archives italiennes Biologie 133:143-148.

14. Cirelli C, Pompeiano M, Tononi G (1995) Sleep deprivation and c-fos expression in the rat

brain. J Sleep Res 4: 92-106.

15. Pompeiano M, Cirelli C, Arrighi P, Tononi G (1995) c-Fos expression during wakefulness and

sleep. Neurophysiol Clin, 25: 329-341.

16. Cirelli C, Pompeiano M, Tononi G (1995) In vivo antisense approaches to the role of immediate

early gene expression in the brain. Regulatory Peptides 59: 151-162.

17. Tononi G, Cirelli C, Pompeiano M (1995) Changes in gene expression during the sleep-waking

cycle: a new view of activating systems. Archives italiennes Biologie 134: 21-37.

18. Tranque P, Crossin KL, Cirelli C, Edelman GM, Mauro VP (1996) Identification and

characterization of a RING-finger gene (C-RZF) expressed in chicken embryo cells. Proc Natl

Acad Sci USA 93: 3105-3109.

19. Cirelli C, Pompeiano M, Tononi G (1996) Neuronal gene expression in the waking state: a new

role of the locus coeruleus. Science 274: 1211-1215.

20. Pompeiano M, Cirelli C, Ronca-Testoni S, Tononi G (1997) NGFI-A expression in the rat brain

after sleep deprivation. Molecular Brain Res 46: 143-153.

21. Cirelli C, Tononi G (1998) Changes in protein phosphorylation in the brain during the sleep-

waking cycle and after lesions of the locus coeruleus. Sleep Research Online 1: 11-18.

15

22. Cirelli C, Tononi G (1998) Differences in gene expression between sleep and waking as

revealed by mRNA differential display. Molecular Brain Res, 56: 293-305.

23. Cirelli C, Tononi G (1999) Differences in gene expression between sleep and wakefulness.

Annals of Medicine 31: 39-46.

24. Cirelli C, Tononi G (1999) Differences in brain gene expression between sleep and waking as

revealed by mRNA differential display and cDNA microarray technology. J Sleep Res, 8:

Suppl.1.

25. Cirelli C, Shaw PJ, Rechtschaffen A, and Tononi G (1999) No evidence of brain cell

degeneration after long-term sleep deprivation in rats. Brain Res 840:184-193.

26. Tononi G, Cirelli C (1999) The Frontiers of Sleep, Trends in Neuroscience 22: 417-418

27. Shaw PJ, Cirelli C, Greenspan RJ, Tononi G (2000) Correlates of sleep and waking in

Drosophila melanogaster. Science 287: 1834-1837.

28. Cirelli C, Tononi G (2000) On the functional significance of c-fos induction during the sleep-

waking cycle. Sleep 23: 453-469.

29. Tononi G, Cirelli C (2000) Some considerations on sleep and neural plasticity. Archives

italiennes Biologie 139: 221-241.

30. Cirelli C, Tononi G (2000) Differential expression of plasticity-related genes in waking and

sleep and their regulation by the noradrenergic system. Journal of Neuroscience 20: 9187-9194.

31. Cirelli C, Tononi G (2000) Gene expression in the brain across the sleep-waking cycle. Brain

Research 885: 303-321.

32. Greenspan RJ, Tononi G, Cirelli C, Shaw PJ. Sleep and the fruit fly. Trends in Neuroscience 24:

142-145, 2001.

33. Tononi G, Cirelli C (2001) Modulation of brain gene expression during sleep and wakefulness:

A review of recent findings. Neuropsychopharmacology 25(5):S28-S52.

34. Cirelli C, Tononi G (2001) The search for the molecular correlates of sleep and wakefulness.

Sleep Medicine Review 5: 399-410.

35. Cirelli C (2002) How sleep deprivation affects gene expression in the brain: a review of recent

findings. J Applied Physiology 92: 394-400.

36. Cirelli C (2003) Searching for sleep mutants of Drosophila melanogaster. Bioessays 25: 940-

949.

37. Tononi G, Cirelli C (2003) Sleep and synaptic homeostasis: A hypothesis. Brain Research

Bulletin 62: 143-150.

38. Cirelli C, Gutierrez CM, Tononi G (2004) Extensive and divergent effects of sleep and

wakefulness on brain gene expression. Neuron 41: 35-43, 2004.

39. Gopalakrishnan A, Ji LL, Cirelli C (2004) Oxidative stress and cellular damage after sleep

deprivation. Sleep 27: 27-34.

40. Cirelli C, Tononi G (2004) Uncoupling proteins and sleep deprivation. Archives Italiennes de

Biologie 142: 541-549.

16

41. Huber R, Hill S, Holladay C, Biesiadecki M, Tononi G, Cirelli C (2004) Sleep homeostasis in

Drosophila melanogaster. Sleep 27: 628-639.

42. Cirelli C, Tononi G (2004) Locus ceruleus control of state-dependent gene expression. J of

Neuroscience 24: 5410-5419.

43. Salbaum JM, Cirelli C, Walcott E, Krushel LE, Edelman GM, Tononi G (2004) Chlorotoxin-

mediated disinhibition of noradrenergic locus coeruleus neurons using a conditional transgenic

approach. Brain Research, 1016: 20-32.

44. Cirelli C (2005) A molecular window on sleep: Changes in gene expression between sleep and

wakefulness. The Neuroscientist, 11: 63-74.

45. Cirelli C, Bushey D, Hill S, Huber R, Kreber R, Ganetzky B, Tononi G (2005) Reduced sleep in

Drosophila Shaker mutants. Nature, 434: 1087-1092.

46. Cirelli C, Lavaute TM, Tononi G (2005) Sleep and wakefulness modulate gene expression in

Drosophila. J of Neurochemistry 94:1411-1419.

47. Cirelli C, Huber R, Gopalakrishnan A, Southard T, Tononi G (2005) Locus Ceruleus control of

slow wave homeostasis. J of Neuroscience 25:4503-4511.

48. Tononi G, Cirelli C (2006) Sleep function and synaptic homeostasis. Sleep Medicine Review,

10:49-62.

49. Cirelli C, Faraguna U, Tononi G (2006) Changes in brain gene expression after long-term sleep

deprivation. J of Neurochemistry 98:1632-1645.

50. Cirelli C (2006) Cellular consequences of sleep deprivation in the brain. Sleep Medicine

Review, 10: 307-321.

51. Cirelli C (2006) Sleep disruption, oxidative stress, and aging: new insights from fruit flies. Proc

Natl Acad Sci USA, 103: 13901-13902.

52. Huber R, Tononi G, Cirelli C (2007) Exploratory behavior, cortical BDNF expression and sleep

homeostasis. Sleep, 30: 129-139.

53. Bushey D, Huber R, Tononi G, Cirelli C (2007) Drosophila Hyperkinetic mutants have reduced

sleep and impaired memory. Journal of Neuroscience, 27: 5384-5393.

54. Vyazovskiy VV, Riedner BA, Cirelli C, Tononi G (2007) Sleep homeostasis and cortical

synchronization: II. A local field potential study of sleep slow waves in the rat. Sleep, 30: 1631-

42.

55. Douglas CL, Vyazovskiy VV, Southard TL, Chiu S-Y, Messing A, Tononi G, Cirelli C (2007)

Sleep in Kcna2 knockout mice. BMC Biology, 5(1):42.

56. Jones S, Pfister-Genskow M, Benca RM, Cirelli, C (2008). Molecular correlates of sleep and

waking in the brain of the white-crowned sparrow. J of Neurochemistry, 105: 46-62.

57. Vyazovskiy VV, Cirelli C, Pfister-Genskow M, Faraguna U, Tononi G (2008) Molecular and

electrophysiological evidence for net synaptic potentiation in wake and depression in sleep.

Nature Neuroscience, 11: 200-8.

17

58. Vyazovskiy VV, Cirelli C, Tononi G, Tobler I (2008) Cortical metabolic rates as measured by

2-deoxyglucose-uptake are increased after waking and decreased after sleep in mice. Brain

Research Bulletin, 75: 591-597.

59. Faraguna U, Vyazovskiy VV, Nelson AB, Tononi G, and Cirelli C (2008) A causal role for

BDNF in the homeostatic regulation of sleep. J of Neuroscience, 28: 4088-4095.

60. Jones S, Pfister-Genskow M, Cirelli C, Benca RM (2008) Changes in brain gene expression

during migration in the white-crowned sparrow. Brain Research Bulletin, 76(5):536-44.

61. Jones S, Vyazovskiy VV, Cirelli C, Tononi G, Benca RM (2008) Homeostatic regulation of

sleep in the White-crowned sparrow (Zonotrichia leucophrys gambelii). BMC Neuroscience, 9:

47.

62. Cirelli C, Tononi G. (2008) Is sleep essential? Plos Biology, 6: e216.

63. Cirelli C, Bushey D (2008) Sleep and wakefulness in Drosophila melanogaster. Annals New

York Academy of Science, 1129:323-9.

64. Bushey D, Tononi G, Cirelli C (2009) The Drosophila Fragile X mental retardation gene

regulates sleep need. J of Neuroscience, 29:1948-61.

65. Vyazovskiy VV, Faraguna U, Cirelli C, Tononi G (2009) Triggering slow waves during NREM

sleep in the rat by intracortical electrical stimulation: effects of sleep/wake history and

background activity. J Neurophysiology, 101:1921-31.

66. Gilestro G, Tononi G, Cirelli C (2009) Widespread changes in synaptic markers as a function of

sleep and wakefulness in Drosophila. Science, 324:109-12.

67. Hanlon EC, Faraguna U, Vyazovskiy VV, Tononi G, Cirelli C (2009) Effects of skilled training

on sleep slow wave activity and cortical gene expression in the rat. Sleep, 32: 719-729.

68. Cirelli, C (2009) The genetic and molecular regulation of sleep: from fruit flies to humans.

Nature Reviews Neuroscience, 10: 549-560.

69. Vyazovskiy VV, Olcese U, Lazimy YM, Faraguna U, Esser SK, Williams JC, Cirelli C, Tononi

G (2009) Cortical firing and sleep homeostasis. Neuron, 63: 865-878.

70. Cirelli C, Pfister-Genskow M, McCarthy D, Woodbury R, Tononi G (2009) Proteomic profiling

of the rat cerebral cortex in sleep and waking. Archives italiennes de biologie, 147: 59-68.

71. Landsness EC, Crupi D, Hulse BK, Peterson MJ,

Huber R, Ansari H, Coen M, Cirelli C, Benca

RM, Ghilardi MF, Tononi G (2009) Sleep-dependent improvement in visuo-motor learning: a

causal role for slow waves. Sleep, 32: 1273-1284.

72. Dash MB, Douglas CL, Vyazovskiy VV, Cirelli C, Tononi G (2009) Long-term homeostasis of

extracellular glutamate in the rat cerebral cortex across sleep and waking states. J of

Neuroscience, 29: 620-629.

73. Weber B, Schaper C, Bushey D, Rohlfs M, Steinfath M, Tononi G, Cirelli C, Scholz J, Bein B

(2009) Increased Volatile Anesthetic Requirement in Short-sleeping Drosophila Mutants.

Anesthesiology, 110: 313-316.

74. Szabo ST, Machado-Vieira R, Yuan P, Wang Y, Wei Y, Falke C, Cirelli C, Tononi G, Manji

HK, Du J (2009) Glutamate receptors as targets of protein kinase C in the pathophysiology and

treatment of animal models of Mania. Neuropharmacology, 56: 47-55.

18

75. Faraguna U, Nelson A, Vyazovskiy VV, Cirelli C, Tononi G (2010) Unilateral Cortical

Spreading Depression Affects Sleep Need and Induces Molecular and Electrophysiological

Signs of Synaptic Potentiation In Vivo. Cerebral Cortex, 20: 2939-47.

76. Bushey D, Hughes KA, Tononi G, Cirelli C (2010) Sleep, aging, and lifespan in Drosophila.

BMC Neuroscience, 11:56.

77. Liu ZW, Faraguna U, Cirelli C, Tononi G, Gao XB (2010) Direct evidence for wake-related

increases and sleep-related decreases in synaptic strength in rodent cortex. J of Neuroscience,

30: 8671-5.

78. Leemburg S, Vyazovskiy VV, Olcese U, Bassetti CL, Tononi G, Cirelli C (2010) Sleep

homeostasis in the rat is preserved during chronic sleep restriction. Proc Natl Acad Sci U S

A, 107: 15939-44.

79. Nelson AB, Faraguna U, Tononi G, Cirelli C (2010) Effects of anesthesia on the response to

sleep deprivation. Sleep, 33: 1659-67.

80. Cirelli C, Tononi G (2011) Molecular neurobiology of sleep. Handbook of Clinical

Neurology, 98: 191-203.

81. Nir Y, Staba RJ, Andrillon T, Vyazovskiy VV, Cirelli C, Fried I, Tononi G (2011) Regional

slow waves and spindles in human sleep. Neuron, 70: 153-69.

82. Bushey D, Cirelli C (2011) From genetics to structure to function: exploring sleep in

Drosophila. International Journal of Neurobiology, 99:213-44.

83. Vyazovskiy VV, Olcese U, Hanlon EC, Nir Y, Cirelli C, Tononi G (2011) Local sleep in

awake rats. Nature, 472: 443-7.

84. Bushey D, Tononi G, Cirelli C (2011) Sleep and Synaptic Homeostasis: Causal Evidence in

Drosophila. Science, 332: 1576-81.

85. Landsness EC, Ferrarelli F, Sarasso S, Goldstein MR, Riedner BA, Cirelli C, Perfetti B,

Moisello C, Ghilardi MF, Tononi G (2011) Electrophysiological traces of visuomotor learning

and their renormalization after sleep. Clinical Neurophysiology, 122: 2418-25.

86. Vyazovskiy VV, Cirelli C, Tononi G (2011) Electrophysiological correlates of sleep

homeostasis in freely behaving rats. Progress in Brain Research, 193: 17-38.

87. Hanlon EC, Vyazovskiy VV, Faraguna U, Tononi G, Cirelli C (2011) Synaptic potentiation and

sleep need: clues from molecular and electrophysiological studies. Current Topics Medical

Chemistry, 11: 2472-82.

88. Maret S, Faraguna U, Nelson AB, Cirelli C, Tononi G (2011) Sleep and waking modulate

spine turnover in the adolescent mouse cortex. Nature Neuroscience, 14: 1418-20.

89. Andrillon T, Nir Y, Staba RJ, Ferrarelli F, Cirelli C, Tononi G, Fried I (2011) Sleep spindles

in humans: insights from intracranial EEG and unit recordings. J of Neuroscience, 31: 17821-

34.

90. Cirelli C (2012) Brain plasticity, sleep and aging. Gerontology 58: 441-5.

91. Tononi G, Cirelli C (2012) Time to be SHY? Some comments on sleep and synaptic

homeostasis. Neural Plast. 2012:415250.

19

92. Dash MB, Cirelli C, Tononi G (2012) Extracellular levels of lactate, but not oxygen, reflect

sleep homeostasis in the rat cerebral cortex. Sleep 35:909-19.

93. Bellesi M, Vyazovskiy VV, Tononi G, Cirelli C, Conti F (2012) Reduction of EEG theta

power and changes in motor activity in rats treated with ceftriaxone. PLoS One 7: e34139.

94. Dash MB, Bellesi M, Tononi G, Cirelli C (2013) Sleep/wake dependent changes in cortical

glucose concentrations. J of Neurochemistry 124: 79-89.

95. Hung CS, Sarasso S, Ferrarelli F, Riedner B, Ghilardi MF, Cirelli C, Tononi G (2013) Local,

experience-dependent changes in the wake EEG after prolonged wakefulness. Sleep, 36: 59-72.

96. Vyazovskiy VV, Olcese U, Cirelli C, Tononi G (2013) Prolonged wakefulness alters neuronal

responsiveness to local electrical stimulation of the neocortex in awake rats. J Sleep Research, in

press.

97. Nelson AB, Faraguna U, Zoltan JT, Tononi G, Cirelli C (2013) Sleep patterns and homeostatic

mechanisms in adolescent mice. Brain Sciences, 3: 318-343.

98. Bellesi M, Pfister-Genskow M, Maret S, Keles S, Tononi G, Cirelli C (2013) Effects of sleep

and wake on oligodendrocytes and their precursors. J Neurosci 33: 14288-300.

99. Tononi G, Cirelli C (2013) Perchance to prune. Sci Am 309: 34-9.

100. Cirelli C (2013) Sleep and synaptic changes. Curr Opin Neurobiol S0959-4388.

101. Nere A, Hashmi A, Cirelli C, Tononi G. Sleep-dependent synaptic down-selection (I):

modeling the benefits of sleep on memory consolidation and integration. Frontiers in Sleep

and Chronobiology 4:143, 2013.

102. Nir Y, Vyazovskiy VV, Cirelli C, Banks MI, Tononi G. Auditory responses and stimulus-

specific adaptation in rat auditory cortex are preserved across NREM and REM sleep. Cerebral

cortex, in press.

103. Frank E, Sidor MM, Gamble KL, Cirelli C, Sharkey KM, Hoyle N, Tikotzky L, Talbot

LS, McCarthy MJ, Hasler BP. Circadian clocks, brain function, and development. Proc Ann

NY Acad, 1306: 43-67.

104. Tononi G, Cirelli C (2014) Sleep and the price of plasticity: from synaptic and cellular

homeostasis to memory consolidation and integration. Neuron 81: 12-34.

105. De Vivo L, Faraguna U, Nelson AB, Pfister-Genskow M, Klapperich M, Tononi G, Cirelli

C (2014) Studying the link between changes in sleep slow wave activity during adolescence and

synaptic pruning in mice. Sleep, 37: 689-700.

106. Vyazovskiy VV, Cui N, Rodriguez AV, Funk C, Cirelli C, Tononi G (2014) The dynamics

of cortical neuronal activity in the first minutes after spontaneous awakening in rats and mice.

Sleep, 37:1337-47.

107. Vorster A, Krishnan H, Cirelli C, Lyons L. Characterization of sleep in Aplysia californica.

Sleep, 37:1453-63.

108. Cirelli C, Tononi G (2014) Letter to the Editor: Sleep and Synaptic homeostasis. Sleep Oct

17. pii: sp-00603-14. [Epub ahead of print]

109. Bellesi M, Riedner BA, Garcia-Molina GN, Cirelli C, Tononi G (2014) Enhancement of

sleep slow waves: underlying mechanisms and practical consequences. Front Syst Neurosci.

20

2014 Oct 28;8:208.

110. Cirelli C, Tononi G (2015) Cortical development, EEG rhythms, and the sleep/wake cycle.

Biol Psych, in press.

111. Bernardi G, Siclari F, Yu X, Zennig C, Bellesi M, Ricciardi E, Cirelli C, Ghilardi MF,

Pietrini P, Tononi G (2015) Neural and behavioral correlates of extended training during sleep

deprivation in humans: evidence for local, task-specific effects. J Neurosci, 35:4487-500.

112. Bushey D, Tononi G, Cirelli C (2015) Sleep- and wake-dependent changes in neuronal

activity and reactivity demonstrated in fly neurons using in vivo calcium imaging. Proc Natl

Acad Sci USA, in press.

Books:

1. Encyclopedia of Sleep, Elsevier, In press (Section Editor).

Journal Issues:

1. Current Sleep Medicine Reports, Issue on Sleep functions (Guest Editor). 2015

Book chapters:

2. Cirelli C, Pompeiano M, Tononi G (1998) Immediate early genes as a tool to understand the

regulation of the sleep-waking cycle: immunocytochemistry, in situ hybridization, and antisense

approaches. In R. Lydic (ed.) Molecular Regulation of Conscious States, CRC Press, invited

contribution, pp. 45-55.

3. Pompeiano M, Cirelli C, Tononi G (1998) Reverse transcription mRNA differential display: a

systematic molecular approach to identify changes in gene expression across the sleep-waking

states. In R. Lydic (ed.) Molecular Regulation of Conscious States, CRC Press, invited

contribution, pp. 157-165.

4. Tononi G, Cirelli C, Shaw PJ (2000) Molecular correlates of sleep, the waking state, and sleep

deprivation. In: Human Frontier Workshop VIII, The Regulation of Sleep, Eds. Borbély A,

Hayaishi O, Sejnowski TJ, Altman JS, HFSP, Strasbourg, pp. 155-168.

5. Cirelli C (2005) Changes in gene expression between sleep, wakefulness, and sleep deprivation.

In: Lung Biology in Health and Disease, Sleep Deprivation, C. Kushida (Ed). Marcel Dekker,

New York, pp. 387-397.

6. Cirelli C, Tononi G (2005). Total sleep deprivation: methodological issues. In: Lung Biology in

Health and Disease, Sleep Deprivation, C. Kushida (Ed). Marcel Dekker, New York, pp.63-79.

7. Cirelli C, Tononi G (2005) Searching for sleep mutants of Drosophila melanogaster. In: Sleep:

Circuits and Functions, P.-H. Luppi (Ed.). CRC Press, Boca Raton, Florida, pp. 145-162.

8. Tononi G, Cirelli C (2005) Changes in gene expression across behavioral states. In: Sleep:

Circuits and Functions, P.-H. Luppi (Ed.). CRC Press, Boca Raton, Florida, pp. 193-200.

9. Tononi G, Cirelli C (2005) A possible role for sleep in synaptic homeostasis. In: The

Physiological Nature of Sleep, PL. Parmeggiani and R. Velluti (Eds), Imperial College Press,

London, pp. 77-101.

10. Tononi G, Cirelli C (2008) Sleep and wakefulness in Drosophila melanogaster. New

Encyclopedia of Neuroscience (Larry Squire, Tom Albright, Floyd Bloom, Fred Gage and Nick

Spitzer, Eds.).

21

11. Benca R, Cirelli C, Rattenborg N, Tononi G (2009) Basic Science of Sleep. In: Comprehensive

Textbook of Psychiatry, B.J. Kaplan and V.A. Sadock (Eds), Lippincott Williams & Wilkins,

Philadelphia, pp.280-294.

12. Cirelli C, Tononi G (2009) The neurobiology of sleep. Neurobiology of mental illness. Third

edition. (Dennis S. Charney, Eric J. Nestler, Eds.), pp. 1370-1386.

13. Cirelli C (2009) Genetics of sleep: animal studies. A Primer of Sleep. Second edition (Sleep

Research Society), pp. 111-117.

14. Cirelli C, Tononi G (2012) Sleep and synaptic homeostasis. In: The Genetic Basis of Sleep and

Sleep Disorders, Thorpy Michael, Shaw Paul, Tafti Mehdi, Editors. University of Cambridge

Press.

15. Tononi G, Cirelli, C. The Neurobiology of Sleep. Neurobiology of Mental Illness. Fourth

Edition (Dennis S. Charney, Eric J. Nestler), pp. 1127-1143, 2013.

16. Cirelli C, Tononi G. Sleep and synaptic homeostasis. The genetic basis of sleep and sleep

disorders. pp. 219-226, 2013.

INVITED RESEARCH PRESENTATIONS

1. Invited Symposium Speaker, 1991, May: Effects of local pontine injection of noradrenergic

agents on desynchronized sleep of the cat. International Symposium on”Neurobiology of the

Locus Coeruleus”, Post Fall, Idaho

2. Invited Symposium Speaker, 1993, March: Differential effects of sleep deprivation on the

expression of different immediate-early genes in the rat brain. International Conference on

“Cellular Consequences of Sleep”, Maui, Hawaii

3. Invited Symposium Speaker, 1993, May: Possible role of the locus coeruleus in c-fos expression

after unilateral labyrinthectomy. International Symposium on “Locus Coeruleus: Development

and Disfuctions”, Orcas Island, Washington

4. Invited Symposium Speaker, 1994, June: Immediate early genes expression in the rat brain after

sleep deprivation and during the spontaneous sleep and waking. VIII Meeting APSS (American

Professional Sleep Societies), Boston

5. Invited Symposium Speaker, 1995, September: How can blocking the expression of a gene help

us to understand sleep? Second International Meeting of the World Federation of Sleep

Societies, Nassau, Bahamas

6. Magisterial Lecturer, 1996, December: A new role for the ascending activating system: the

regulation of gene expression between sleep and waking. Young Investigators in Neuroscience

Meeting, Pisa. Plenary lecture in honor of Prof. G. Moruzzi.

7. Invited Symposium Speaker, 1997, June: Changes in gene expression between sleep and waking

revealed by differential display PCR. XI Annual Meeting APSS, San Francisco.

8. Invited Symposium Speaker, 1998, June: Analysis of brain cell death after long-term sleep

deprivation in rats. XII Annual Meeting APSS, New Orleans.

9. Invited Symposium Speaker, 1999, June: Changes in gene expression in the brain after short and

long-term sleep deprivation. XIII Annual Meeting APSS, Orlando.

22

10. Invited Symposium Speaker, 2000, April: Gene expression analysis in the cerebral cortex as a

function of behavioral states. International CHI Meeting on “Macro results from microarrays”,

Boston.

11. Invited Symposium Speaker, 2000, September: Evaluating the molecular correlates of sleep and

waking, International Congress Sleep Medicine on the Eve of the Third Millenium, Bologna,

Italy.

12. Guest Lecturer, 2001, April: Gene expression in sleep and waking, Harvard University, Boston,

Massachusetts.

13. Invited Symposium Speaker, 2001, July: Molecular correlates of sleep and waking. Gordon

Research Conference on Neural Plasticity. Salve Regina University, Newport, RI.

14. Invited Symposium Speaker, 2001, December: Induction of plasticity-related genes during sleep

and wakefulness, NIMH Workshop on Sleep and Memory, Bethesda, MD.

15. Invited Symposium Speaker, 2002, June: Sleep and genes: insight from different species.

European Sleep Research Society, 16th Meeting, Reykjavik, Iceland.

16. Invited Symposium Speaker, 2003, May: Molecular correlates of sleep and wakefulness.

Gordon Research Conference on Chronobiology. Il Ciocco, Barga, Italy.

17. Guest Lecturer, 2003, September: Extensive and divergent effects of sleep and waking on brain

gene expression. International scientific meeting in honor of Prof. Michel Jouvet, Lyon, France.

18. Invited Symposium Speaker, 2005, January: Sleep genes and the functions of sleep. 38th

Annual Winter Conference on Brain Research, Breckenridge, Colorado.

19. Guest Lecturer, 2005, May: Searching for sleep mutants of Drosophila melanogaster Center for

Sleep and Respiratory Neurobiology at the University of Pennsylvania, Philadelphia.

20. Magisterial Speaker, 2005, June: A molecular window on sleep and waking. APSS Annual

Meeting, Denver, Colorado.

21. Plenary Speaker, 2005, November: Sleep and genes: from mechanism to function. Society for

Neuroscience Meeting, Washington D.C.

22. Guest Speaker, 2005, December: Drosophila sleep and Shaker. Dept of Neurobiology,

Northwestern University, Evanston, IL.

23. Plenary Speaker, 2006, May: Sleep and Genes: from mechanisms to functions. Grass lecture,

Ohio Miami valley Society for Neuroscience Annual Meeting, Miami University, Oxford, OH.

24. Invited Symposium Speaker, 2006, May: Sleep and Genes: from mechanisms to functions.

Wisconsin Symposium on Human Biology, Madison WI.

25. Invited Symposium Speaker, 2006, June: The molecular biology of sleep. Human Brain

Mapping 2006, Florence Italy.

26. Guest Speaker, 2006, October: Drosophila sleep: from genes to functions. Dept of

Neuroendocrinology, University of Lubeck, Germany.

27. Invited Symposium Speaker, 2007, March: Drosophila sleep and potassium channels. Janelia

Farm Conference, Insect Behavior: Small Brains, Big Functions, March 13-15, 2007; Janelia

Farm, Ashburn, VA.

23

28. Guest Speaker, 2007, April: Sleep and genes: from mechanisms to functions. NIDA Cutting

Edge Seminars, Bethesda, MD

29. Invited Symposium Speaker, 2007, May 6-11: Potassium channels and sleep, Gordon

Conference on Chronobiology, Aussois, France.

30. Guest Lecturer, 2007, September: SWA and synaptic plasticity. Zurich University, Zurich,

Switzerland.

31. Guest Lecturer, 2007, October: Gene expression in sleep and waking, Upper Midwest Sleep

Society, Annual Meeting. Minneapolis, Minnesota.

32. Invited Symposium Speaker 2008, March 3-4: Sleep, genes and learning, National Sleep

Foundation Meeting on “The role of sleep in memory and learning”, Washington D.C.

33. Invited Symposium Speaker 2008, March 7-12: Sleep and synaptic plasticity, Keystone

Symposium on “Genetics and Biochemistry of Sleep”, Tahoe City, California.

34. Guest Lecturer, 2008, March 19: Sleep and synaptic plasticity, Morehouse School of Medicine,

Atlanta, Georgia.

35. Guest Lecturer, 2008, April 17: Sleep and synaptic plasticity, University of Toronto, Toronto,

Canada.

36. Invited Symposium Speaker 2008, September 9-13: Molecular consequences of acute and

chronic sleep loss, European Sleep Research Society, 19th

Meeting, Glasgow, Scotland.

37. Invited Symposium Speaker 2008, October 15-17: Molecular correlates of sleep and waking,

Meeting on “Genes at work on time”, Torino, Italy

38. Invited Symposium Speaker 2008, November 15-19: Sleep and synaptic strength, Society for

Neuroscience Meeting, Washington, D.C.

39. Guest Lecturer, 2008, December 1: Sleep and synaptic plasticity. Distinguished Speakers Series,

Keck Center for Behavioral Biology at North Carolina State University, Raleigh, NC.

40. Guest Lecturer, 2008, December 12: Sleep: genetics and mechanisms. Cyclotron Research

Center, University of Liege, Belgium.

41. Invited Symposium Speaker 2009, April 26-28: Fly sleep and synaptic plasticity. Fourth

Conference of the Canadian Sleep Society, Toronto, Canada

42. Invited Speaker, 2009, June 2: “Sleep and synaptic plasticity”, Janelia Farm Conference on

“Sleep in non-mammalian models,” Janelia Farm Campus, Ashburn, Virginia.

43. Invited Speaker, 2009, September 24: “Sleep and Genes”, XXII Symposium of The Signe and

Ane Gyllenberg Foundation, The Many Aspects of Sleep, Hanasaari Congress Center, Espoo,

Finland.

44. Guest Lecturer, 2009, November 20: “Sleep and synaptic plasticity”, Skirball Institute, New

York University School of Medicine, New York NY

45. Invited Symposium Speaker, 2010, February 18: “Cellular consequences of sleep and waking”,

Stanford University, Palo Alto, CA

46. Guest Lecturer, 2010, May 25: “Is sleep essential? Clues from animal models”, University of

Chicago, Chicago, IL.

24

47. Invited Symposium Speaker, 2010, June 20: “Sleep and synaptic plasticity”, Skirball Institute,

New York University School of Medicine, New York NY

48. Invited Symposium Speaker, 2010, June 7: “Local and global regulation of sleep”. Sleep 2010

Annual Meeting APSS, San Antonio, TX.

49. Invited Symposium Speaker, 2010, June 10: “Sleep and energy metabolism”. Sleep 2010

Annual Meeting APSS, San Antonio, TX.

50. Guest Lecturer, 2010, October 5: “Is sleep essential?” Scuola Superiore Sant’Anna, Pisa, Italy.

51. Guest Lecturer, 2010, December 14; “Sleep and synaptic plasticity” Biology Seminar Series,

Caltech, Pasadena, CA.

52. Invited Symposium Speaker, 2011, April 15: “Sleep and aging in flies”. Nestle’ symposium on

aging. Vienna, Austria.

53. Plenary Speaker, 2011, May: “Sleep and plasticity”. Conference on “Research needs for the

problems of children with developmental disorders.” Vancouver, Canada.

54. Guest Lecturer, 2011, October 4; “Sleep and synaptic plasticity” Neuroscience Seminar Series,

Spokane, Washington State University, WA.

55. Guest Lecturer, 2011, Dec 1: “Sleep function and synapses”, Brown University, Providence, RI.

56. Guest Lecturer, 2012, Jan 19: “Sleep and synaptic homeostasis”, Neuroscience Seminar Series,

U of California San Francisco, CA.

57. Invited Symposium Speaker, 2012, May 3: “Sleep and synapses”. Biology of Sleep Symposium,

Max Planck Institute of Psychiatry, Munich, Germany.

58. Invited Symposium Speaker, 2012, Sept 6: “Sleep and the price of wake plasticity”. Kavli Prize

Symposium on Neuroscience, University of Bergen, Norway.

59. Plenary Speaker, 2012, Sept 8: “Wake plasticity and the reasons for sleep”. Closing lecture,

European Sleep Research Society Meeting, Paris, France.

60. Guest Lecturer, 2013 March 18: “Molecular and cellular changes due to sleep and wake”.

Symposium on sleep, University of Bristol, United Kingdom United Kingdom.

61. Plenary Speaker, 2013 March 27: “Sleep: a time for down selection?” Symposium “Solving

the mystery of sleep”. University of Tsukuba, Japan.

62. Guest lecturer, 2013 April 15: “Sleep and synaptic plasticity”. Dept of Integrative

Physiology, U of Colorado at Boulder.

63. Guest lecturer, 2013 December 6: “Sleep and synaptic plasticity”. CUNY, New York, NY.

64. Guest lecturer, 2014 January 21: “Sleep: a time for down-selection?” U Texas Southwestern,

Dallas, Dept of Neuroscience. Dallas, TX.

65. Guest lecturer, 2014 March 27: “Sleep and synaptic homeostasis”. U Oxford, Oxford UK.

66. Guest lecturer, 2014 April 4: “Sleep: a time for downselection?”. U Oslo, Oslo, Norway.

67. Guest lecturer, 2014 April 7: “Sleep: a time for downselection?”. U Bergen, Bergen,

Norway.

25

68. Symposium speaker, 2014 June 1: “Sleep in adolescent mice”. APSS 2014, Minneapolis,

MN.

69. Symposium speaker, 2014 July 19: “Consciousness in sleep”. ASSC 18, Brisbane, Australia.

70. Symposium speaker, 2014 November 7: “Effects of sleep and wake on astrocytic function”.

Salk Institute, La Jolla, CA.

71. Guest Lecturer, 2014 November 13: “Sleep and synaptic homeostasis”. U Michigan, Ann

Arbor, MI.

72. Guest Lecturer, 2015 January 16: “Sleep and synaptic homeostasis: clues from ultrastructural

studies”. U Zurich, Zurich, Switzerland.

RESEARCH SUPPORT

1984-1990 National Fellowship at the Scuola Superiore S.Anna, Pisa,

100% salary support during medical school

1990-1993 National Fellowship at the Scuola Superiore S.Anna, Pisa,

100% salary support during Ph.D. training

1993-1994 Recipient, Post-doctoral fellowship, Italian Space Agency,

Rome, Italy, 100% salary support

Completed

09/26/00–09/25/02 2000 Sleep Medicine Education & Research Foundation

Research Grant Award

“Fatal Familial Insomnia (FFI): Changes in Brain Gene Expression”

C. Cirelli PI

This research has identified genes whose expression is specifically affected in the brain of FFI

patients relative to controls.

05/01/02-12/31/04 UW 161-9856, UW/Howard Hughes Faculty Development Program

C. Cirelli PI

This start-up funding was used to set-up the mutagenesis screening program.

05/15/01-04/30/05 RO1 NIMH MH65135

“Functional consequences of sleep deprivation”

G. Tononi PI

Role: Co-Investigator

26

The major goal of this project was to verify and evaluate the expression of arylsulfotranferase

(AST) and its effects on sleep deprivation.

03/10/02-09/30/03 Phase I- DAAD19-02-1-0036 DARPA

“Rapid Discovery of Continuous-Performance Compounds and

Powernap Compounds”

G. Tononi PI

Role: Senior Investigator

My role in the project has been to coordinate the screening of > 8000 mutant fly lines and to

identify several sleep mutant lines that are either short sleepers and/or are resistant to the effects

of sleep deprivation.

03/15/02-09/30/03 Phase I- DAAD19-02-1-0041 DARPA

“Avian Models of Sustained Wakefulness”

R. Benca PI

Role: Senior Investigator

This project has shown that, during migration, birds can dramatically restrict their need for sleep

for several days and yet carry out tasks flawlessly. I coordinated the identification and analysis of

specific brain transcripts that are upregulated during migration.

01/01/05–10/31/05 Phase I- DoD SBIR grant 48019-LS-SB1

Department of Defense Small Business Innovative Research Grant

“Identification and Characterization of Molecular Inhibitors of

Cognitive Performance: A Large-Scale Proteomic Analysis in Sleep

Deprived Flies, Rats, and Sparrows”

C. Cirelli PI

Small business partner: Ciphergen Biosystems, Inc. The goal of this project is to identify proteins

selectively expressed in the brain of animals that show resistance to sleep deprivation.

04/01/04 - 03/31/07 Phase II- DAAD19-02-1-0036 DARPA

“From 24/7 Flies and Birds to 24/7 Humans – The UW Continuous

Performance Project ”

C. Cirelli (PI, project I), R. Benca (PI, project II), G. Tononi PI

(project III)

This Phase II proposal includes 3 projects, lead by 3 PIs, and results from the combination of two

independent projects in Phase I (now completed): “Rapid Discovery of Continuous Performance

and Power-Nap Compounds” and “Avian Models of Sustained Wakefulness”. The overall goal for

Phase II was to characterize the molecular mechanisms underlying the ability of specific fly lines

and migratory birds to sustain prolonged sleep loss without cognitive impairment. I was the PI for

27

project I, which involved the characterization of fly sleep mutant lines, including the Shaker mutant

that was recently published.

11/01/05–10/31/07 Phase II- DoD SBIR grant 48019-LS-SB1

Department of Defense Small Business Innovative Research Grant

“Identification and Characterization of Molecular Inhibitors of

Cognitive Performance: A Large-Scale Proteomic Analysis in Sleep

Deprived Flies, Rats, and Sparrows”

C. Cirelli PI

Small business partner: Ciphergen Biosystems, Inc. The goal of this project was to identify proteins

selectively expressed in the brain of animals (flies, rats, and sparrows) that show resistance to sleep

deprivation.

08/01/05-07/30/10 RO1 NIGMS GM075315

“Characterization of Sleep Mutants of Drosophila”

C. Cirelli PI

The major goal of this project was to characterize 3 short sleeper mutants identified through the mutagenesis screening.

08/01/07-07/31/11 NIMH P20MH077967 Tononi, Center Director

“Sleep function and synaptic homeostasis: linking basic

neurobiology and mental health.”

The goal of this Conte Centers for Neuroscience Research project is to test the synaptic

homeostasis hypothesis using molecular, imaging, electrophysiological and clinical approaches. The

Center grant application includes 4 projects, each lead by a different PI. My project is to determine

whether sleep is associated with molecular signs of synaptic depression. Tononi, Center Director;

Benca, Cirelli, Raichle, Tononi, PIs.

Ongoing

09/01/10-05/31/15 1R01MH091326-01 Cirelli, Tononi (MPI)

“Synapses and Sleep in Neurodevelopment: a crucial interaction at

a critical time.”

The goal of this grant is to establish slow wave activity during NREM sleep as a marker to assess

cortical maturation during development, and to assess the role of the sleep/wake cycle in regulating

synaptogenesis and synaptic pruning during development.

28

07/01/2013-06/30/2018 1R01MH099231-01A1 (NIH (NIMH) Tononi,Cirelli (MPI)

“The cost of plasticity: from cells to systems”

This proposal will test the hypothesis that acute sleep deprivation and chronic sleep restriction

may result, especially in vulnerable individuals such as adolescents, in cognitive impairments,

frontal cortex malfunction, and cellular damage.

09/30/2014-08/30/2019 P01 NS083514-01A1 (NIH (NINDS) Tononi (PI)

“Do single neurons need to sleep, and why?”

This proposal will determine whether sleep can occur locally in an awake brain, and shed light

on the price of wakefulness and the restorative functions of sleep, in vivo and at the single cell level.

29

MANUSCRIPTS REVIEWED FOR:

American Journal of Physiology

American Journal of Psychiatry

BMC Neuroscience

Brain Research

Brain Research Bulletin

Current Biology

European Journal of Neuroscience

Journal of Applied Physiology

Journal of Neurochemistry

Journal of Neuroscience

Journal of Physiology

Journal of Sleep Research

Molecular Brain Research

Nature

Nature Neuroscience

Neuron

Neuropsychopharmacology

Neuroscience

Neuroscience Letters

PNAS

Progress in Neurobiology

Sleep

Sleep Medicine Review

Science

Science Advances

Trends in Neuroscience