Brain Midline1

Midline MRI

Brain Diagram

TemporalLobe

LobeFrontal

Cerebral Cortex

ParietalLobe

LobeThalamus

Hypothal.

Corticospinal Tract

Cervical armmuscles

Thoracic

Lumbosacral

Spinal Cord

Medulla

BasalGanglia

SC

ICMidbrain

PinealOcciptal

CerebellumPons

Pituitary

Neuron Numbers:

100 Billion in cerebellum

25 Billion in cerebral cortex

1 Billion in rest of brain

126 Billion in brain

BBB1

nuc

Redrawn after figure on page 76 of "The Blood Brain Barrier" by GW Goldstein and AL Betz (Sci. Amer. 255:74−83, 1986)

Astrocyte Foot Processes

EndothelialCell Basement

Membrane

Tight Junctions here

CapillaryLumen

CSF Circulation

arachnoidtrabeculae

SuperiorSagittalSinus

CSF leaving subarachnoid space and entering the venous circulation in the superior sagittal sinus via arachnoid villi.

Cerebrum

Corpus Callosum

Plexus secretesCSF intoventricles

Cerebellum

CSF leaving ventriclesand entering subarachnoidspace

Third Ventricle

Cerebral Aqueduct

Fourth Ventricle

Brain Stem

sulcus

gyrus

endosteal dura

blood vesselon top of pia

Dura (solid line)

Arachnoid (dashed line)

Pia (dash−dot−dot line)

Spinal Cord

meningeal dura

SpaceSubarachnoid

Choroid

Vertebrobasilar Circulation

Cerebral Circulation

Middle cerebral a.

Posterior cerebral a.

Anterior cerebral a.

Cerebral Circulation Territories

OccipitalLobe

ParacentralLobule

Cut Surfaceof Midbrain

Optic X

(Fus

iform

g.)

Piriform

Perirhinal

Entorhinal

Parahippocampal

A

H

H

C

Rec

tus

g.

Infe

rior

Tem

pora

l g.

Occ

ipito

−Tem

pora

l s.

Occ

ipito

−Tem

pora

l g.

Col

late

ral s

.R

hina

l s.

Calcarine f.

(Inf

erio

r T

empo

ral s

.)

Orbital gyri

Olfactory bulb

Par

ahip

poca

mpa

l g.

Uncus

Inferior Parietal s.

Pre

cent

ral s

.

Superior T

emporal g.

Middle Temporal g.

Inferior T

emporal g.

marginal g

Angular g.Supra−

Precuneus

Cuneus

Lingula

Parahippocampal g.

Pre

cent

ral

g.

Pos

tcen

tral

g.

Superior Parietal Lobule

Superior T

emporal s. Cingulate g.

Superior Frontal g.

Cingulate s.

Calcarine s.

Superior Frontal g.

Middle Frontal g.

Middle Temporal s.

Cen

tral s

.

Superior Frontal s.

Inferior Frontal s.

Inferior Frontal g.

Pos

tcen

tral

s.

Parie

to−o

ccip

tal s

.

Occipito−temporal s.

Occipito−temporal g.

Collateral s.

Rhinal s.

GliaDuring braindevelopmentastrocytes known as radial glia act as scaffolds along which neurons and other cells migrate.

swell in

cytotoxic

edema Astrocyte foot processes

induce endothelial tight

junctions (etj) of BBB.

"Reactive" astrocytes(gliosis) GFAP

+

Astrocytes (A) encapsulatesynapses, restricting diffusionof neurotransmitters. They alsotake up GABA, glutamate, andother neurotransmitters that arereleased. In addition, theyremove excess K from the extracellular space by their

Microglia (M) arise from bone marrowderived monocytes (mesoderm) thattake up residence in CNS where they serve as "macrophage sentries" thatmonitor state of brain and mediate interactions with immune system.

Oligodendrocytes (O) and astrocytes (A) arise from localproliferation of migratory, common precursor cells fromneuroepithelium (ectoderm) of ventricles and central canal.Oligodendrocytes can myelinate as many as 50 CNS axonsover the long (+5 yr) and regionally varied period of braindevelopment.

Cross section of axonmyelinated by anoligodendrocyte.

NeuronalInjury (1)

NeuronalInjury(2)

fibrous astrocytein white matter

"resting" stateameboid phagocytic

activated state

proliferation

hypertrophy

proliferation

GM−CSF

Pia

Glia Limitansprotoplasmicastrocytes ingray matter

NGFCNTF

bFGFS100−

NO

Neuron

NO

vasodilation

K+

A

A

A

A

A

MAOA

A

O

O

O

ECM

K+

ramified

M

M

M

M

M−CSF

NGF, FGF

IL−1βTGF

TNFα

T cells

etj

gap junctions

β

lactate

CO2

bFGF

A

A

+"inward rectifier" K channels.

MMHCIIMHCII

MHCII

ROS, NO, PGComplement, proteasessynaptic stripping

α,TGFIL−1, IL−6, TNF β1

Neuron

myelin sheath

cell body

axon from another neuron

dendrites

synapse

axon

axon continues

nuc.

axon

spines

axon

synaptic cleft(10 nm)

postsynaptic receptorscan open or close ion channels

dendriteshaft

synaptic vesiclesaxon terminal

neurotransmitter

Spinal Cord Tracts

ColumnsDorsal

CST

DSCT

VSCT

STT

RtST, VST, TST

RST

5 MOTOR 5 SENSORY

FG FC

10 Important Tracts

ColumnsDorsal

CST

STT

1 MOTOR 2 SENSORY

FG FC

3 REALLY IMPORTANT Tracts

Cranial Nerve Organization into Functional Groups

Efferents (E) Afferents (A)GSE General Somatic → myotome skeletal muscle GVA General Visceral ← heart, stomach, etc.SVE Special Visceral → arch skeletal muscle SVA Special Visceral ← tasteGVE General Visceral → smooth & cardiac muscle, glands GSA General Somatic ← face

SSA Special Somatic ← cochlea, semicirc. canals

sulcus limitans

Brain StemSpinal Cord

GSEGVE

GVA

SVE

SSA

GSA

SVA

GVA

GVE

GSA

Basal

Alar BasalAlar

IVth Vent.

GSE

midline

GVEGSE

GVA/SVAGSA

SSA

MOTOR

SENSORY

Medulla Pons Midbrain

Inf OliveSup. Coll.

Inf. Coll.

SVE

SpV

NA− (XI, X, IX)

DMN−XXII VI

motVII

IS

motV

SS EWIII

SOL−(XI, X, VII)

VIII

PrV MesV

IV

Cranial Nerve Name GSE SVE GVE GSA GVA SVA SSAIII Oculomotor x xIV Trochlear xV Trigeminal x x

VI Abducens xVII Facial x x x x x

VIII Vestibulocochlear xIX Glossopharyngeal x x x x xX Vagus x x x x x

XI Accessory x xXII Hypoglossal x

Lateral Medullary Syndrome (Wallenberg)

Pathways in the Brain Stem

Corticospinal Tract, Dorsal Column/Medial Lemniscus, Spinothalamic Tract

ColumnsDorsal

Medulla

PonsMidbrain

CST

Spinothalamic Tract

Pyramid

Medial Lemniscus

Crus Cerebri

NG,NC

MLF and Lateral Vestibulospinal Tract

Semicircular canals

46

Vestibular nuclei

3

lateral vestibulospinal tr.

PPRF

AP

H

descending MLF ascending MLF

PPRF and Ascending MLF

46 3ascending MLF

PPRF

Trigeminal

Trigeminal pain fibers join spinothalamic tract

(VTT runs with medial lemniscus)Ventral Trigemino−thalamic tract

muscles of mastication (1st arch)

Trigeminal Nerve Organization

midline

GSASpV PrV MotV (SVE)

MesVoralisinterpolariscaudalis

spinal trigeminal tract

Trig. Ganglion

Ia from spindles in muscles of mastication(afferents of monosynaptic jaw closing reflex,similar to monosynaptic patellar reflex)

SpV caudalisrelays pain/temp(like spinothalamic)

PrV relaysproprioception(like gracilis/cuneatus)

VPM

VPM

crossed Dorsal Trigemino−thalamic tract

uncrossed Dorsal Trigemino−thalamic tract

(DTTs run near central tegmental trs.)

Medulla MidbrainPons

Thalamus

OpticNerves

OpticTract

SuperiorColliculus

PosteriorCommissure

PretectalArea

LateralGeniculate

Edinger−WestphalNucleus

Oculomotor Nerve

Ciliary Ganglion

EyesRetina

Adapted from Kourouyan, H. D.. and Horton, J. C., 1997, Transneuronal retinal input to the primateEdinger−Westphal nucleus. J. Comp. Neurol. 381:68−80.

Pupillary Light Reflex Circuitry

II II

III III

Midbrain

Pupillary Cons.

PAG

Locus Ceruleus/Raphe

Cortex

Cut Surfaceof Midbrain

H

Parahippocampal g.

Occipito−Temporal g.

Pre

cent

ral g

.

Middle Temporal g.

Marginal br.

Cuneus

Piriform

Parahippocampal

Rec

tus

g.

Calc. f.

Orbital gyri

Olfactory bulb

Optic X

C

H

Precuneus

Lingula

Paracentral

Inferior T

emporal g.

Superior T

emporal g.

Middle Frontal g.

Pos

tcen

tral

g.

Subcallosal g.

Anterior C

ingulate g. Posterior Cingulate g.

Uncus

A

Infe

rior

Tem

pora

l g.

Occ

ipito

−T

empo

ral (

fusi

form

) g.

Par

ahip

poca

mpa

l g.

Pre

cent

ral s

.

Cen

tral

s.

Supramarginal

Superior Parietal Lobule

Inferior T

emporal s.

Superior T

emporal s.Superior F

rontal g.

Inferior F

rontal g.

Superior Frontal s.

Inferior F

rontal s.

Intraparietal s.Angular g.

Pos

tcen

tral

s.

Occipital g.

Superior Frontal g.

Collateral s.

Parie

to−O

ccip

ital s

.

Calcarine f.

Cingulate s.

Rhi

nal s

.

Occ

ipito

−T

empo

ral s

.

Col

late

ral s

.

Par.−Occ. s.

Perirhinal

Entorhinal

Central s.

Cerebellum

MCP

ICP

SCP

Cortex

TemporalLobe

LobeFrontal

Cerebral Cortex

ParietalLobe

LobeThalamus

Hypothal.

Corticospinal Tract

Cervical armmuscles

Thoracic

Lumbosacral

Spinal Cord

Medulla

BasalGanglia

SC

ICMidbrain

PinealOcciptal

Pons

Pituitary

Neuron Numbers:

100 Billion in cerebellum

25 Billion in cerebral cortex

1 Billion in rest of brain

126 Billion in brain

Cerebellum

Thalamus

Internalcapsule

CorpuscallosumA B Caudate

Lateral

Hypothalamus

3V

M

A

L

Dorsal

ventricle

thalamus

Globuspallidus

MGLG

Pul

VL

VAAV

MD

ILN

VPL/VPM

Visual

SomatosensoryMotorPremotor

Prefrontal

Calcarinesulcus

Cingulataesulcus

Central sulcus

A

B

C

Auditory

AssociationCortex

LP/PUL

LP/PUL

VAVLVPL/VPM

ZI

PULLP

LDMDl

MDm

ANT

ET

MGLG

IML

MEDIAL

LATERAL

ANT.

METATHALAMUS

3V

"Compartments"Nuclei

Thalamic Inputs on Horizontal Section

Thalamic Organization on Frontal Section

MIDILN

R Dorsal

Ventral

Nuclei Inputs

Retina

(VPL)

BasalMamm

+

(VPM)

Sol N

body

hipp

ganglia

spinothal trMedial lemn/

Sup coll

Superiorcerebellarpeduncle

Trigemthal

Superior colliculus

Inf coll

PUL

VPL

VPM

MG

VLVA

MDl−ILN MDl−ILN

MDm−MIDOLF

PUL

ANT/LD

VPLVL

VA

Lateral View Medial View

LG LG

Thalamic Outputs to Cortex

Thal-BG

Splenium ofCorpusCallosum

Thalamus

Genu ofCorpusCallosum

CL

GPPost

Caudate

Putamen

LV

LV

Ant

Genu

Basal Ganglia Circuitry

Indirect Pathway (D2 DA receptor, GABA−ENK) inhibits movement.Direct Pathway (D1 DA receptor, GABA−SP) facilitates movement.

D1

excitatory synapseinhibitory synapse

Internalcapsule

Dopaminergicnigrostriatal pathway

Substantianigra

Movement

GPl

XPD

XHD

motor cortexPremotor/supplementary

Ventral anterior/

Entire cerebral cortex

Striatum

Globuspallidus

(caudate,putamen)

Subthalamic nucleus

GPm ventral lateralthalamus

DBS

Parkinson’s Disease (PD): Loss of nigrostriatal dopamine dysfacilitates Direct Pathwayand disinhibits Indirect Pathway, both REDUCING movement (akinesia, bradykinesia).

D2

direct

indirect

Deep brain stimulation (DBS) of the subthalamic nucleus is a new therapy for PD

akinesia and facilitates movement.Huntington’s Disease (HD): Selective loss of striatal neurons projecting to GPl reducesinhibitory effect of Indirect Pathway, INCREASING movement (chorea).

that reduces excitation of GPm, thereby diminishing its inhibitory output, which relieves

(Houk, JC and Rymer, WZ 1981. Neural control of muscle length and tension. Handbook of Physiology.Section 1. The Nervous System, Vol. II, Motor Control, Part 1. Am Physiol Soc, Bethesda, pp 257−323)

Load

Gammamotor neurons

Alpha

Descending control signals

Length Force

ServoMotor

motor neurons

Muscle

spindlesMuscle Tendon

organs

Motor Pathways

system in the monkey, I and II. Brain 91:1−14 and 14−33, 1968.)(Lawrence, D.G. and Kuypers, H.G.J.M. The functional organization of the motor

CST

RtST, VST, TST

distax pr

RST

synapse

effectsBrain Stem

Ret. Form.Upper

Motor

Neuron

α

+

Strictly defined, spasticity is a velocity dependent increase in resistanceof a passively stretched muscle that is often associated with a suddenmelting of resistance during stretch (clasp knife reflex).

Spasticity is caused by an upper motor neuron lesion that interruptsboth the corticospinal tract (CST) and the descending cortical projections to the brain stem reticular formation cells that give rise to the dorsolateral reticulospinal tract (DLRtST). The DLRtST descendsin the dorsolateral funiculus and provides tonic inhibition (NE, 5HT) of spinal interneurons activated by Group II, III, and IV afferents.RELEASE from this inhibition causes spasticity’s hypertonia andhyperreflexia because of selective facilitation of FR and FF alpha motorneurons. The clasp knife reflex occurs because of loss of inhibition ofinhibitory interneurons relaying group II, III, and IV afferent signals activated at relatively high thresholds.

(see Burke et al., Brain 95:31−48, 1972 for more info.)

muscle/joint afferents

(high threshold)

Ia

DLRtST

muscle

CST

II,III,IV

5HTNE

Spasticity = exaggerated stretch reflexes and hypertonia, along with the clasp−knife reflex.

Basal Ganglia Cerebellum

Motor Cortex

Entire Cerebral Cortex

VA−VL

Movement in PD and Cerebellar Damage

Flowers, K. 1975. Neurology 25:413

B. Cerebellar

C. PD

A. Normal

layers

46

4

6

17

18

39

I

V

IIIII

IV

VI

Supragranular = Cortico−cortical"Association Cortex"

IIIIII

IV

VVI

Granular = Input or "Sensory Cortex"

Infragranular = Output or "Motor Cortex"

Outputs from cortical layers Inputs to cortical layers

Contralateral Cortex (callosal)

Ipsilateral Cortex

Striatum, Brainstem, Spinal Cord

Thalamus and Claustrum

Non−specific (locus ceruleus, raphe, nucleus basalis)

Cortico−cortical

Thalamus

Cerebral Cortex Layers

Cerebral Cortex Cytoarchitecture

Cortex Big Picture

Vision

Body

VisionEyes−Head

Viscera/Hormones

Eyes−Head

Where?

What?

Body

What?

Move Speech

SpeechProduction

Hearing

What?

Perception

chiasm

EYE

x

LG

OR

Calcarine Cortex

LVF RVF

Left Right

Visual Cortex

5°20°

Calcarinesulcus

Cingulatesulcus

Parieto−

sulcusoccipital

visual cortex (area 17). It is organized into a map or "representation" of thecontralateral visual field in which the fovea is represented most posteriorly.Note the UPPER hemifield maps to the LOWER bank of the calcarine sulcus.

The upper and lower banks of the calcarine sulcus are the location of the primary

Visual Field

11

12

8

73

4

1

2

5

6

10

9

1

26

59

10

pial surface of "hypercolumn" that processes visual input fromone small area ofcontralateral visual

Enlarged view of

Visual Cortex

Corpus Callosum

field. Hypercolumnextends from pia toto white matter.

All cells in a hypercolumn respond to same part of visual field, but eachhypercolumn can be subdivided into two "ocular dominance columns" in whichcells respond more strongly to inputs from left or right eye (L, R). In addition, each hypercolumn can also be subdivided into many "orientation columns" wherecells respond more strongly to lines or edges with a particular orientation (vertical,horizontal, or oblique, depicted as short line segments inside hypercolumn).

where cells respond to color but not orientation. The visual cortex begins process of making "lines and shapes" out of retinal "points," allowing us to see Seurat’s famous painting.

Finally, each hypercolumn also contains color−sensitive "blobs" (shaded ovals)

L R

odpattern

Cingulatesulcus

Parieto−

sulcusoccipital

Corpus Callosum

Calcarinesulcus

Simplified view of overall patternof ocular dominance "stripes" in primary visual cortex. Light bandrepresents LEFT eye dominance, andblack band represents RIGHT eyedominance. Small white rectanglecorresponds to hypercolumn on previous figure. Note that stripes"flow" into calcarine sulcus and then reemerge onto cortical surface.

Hypothalamus-Midsag

Anterior Commissure

Paraventricular N.

Anterior N.Preoptic AreaLamina TerminalisDorsomedial N.Ventromedial N.

Supraoptic N.Suprachiasmatic N.

Optic Chiasm

Anterior LobePituitaryPosterior Lobe

Median EminenceArcuate N.

MammillaryBody

Posterior N.

Hypothalamic Sulcus

Massa Intermedia

Mammillo−thalamic tr.

Fornix

Portal SystemHypothalamo−Hypophyseal

Hypothalamus-Xsec

3V

Caudate

Internal

AnteriorCommissure

Corpus Callosum

Mammillo−Thalamic Tr.

Thalamus

GlobusPallidus

Putamen

Basal Forebrain

Fornix

FornixVentricleLateral

Hypothalamus

Optic Tracts

Amygdala

Ant

Capsule

Limbic System

PiriformCortex

OlfactoryBulb

PosteriorCingulate

HippocampalFormation

CortexEntorhinal

Amygdala

Olf. Tr.

Septal Area

CingulateAnterior

CC

Ant.Nuc.ST

AC

Fornix

MTT

Body

Hypothalamus

VMNSubcallosalGyrus

Mamm.

Hippocampal Trisynaptic Pathway

Temporal Horn

Ventricleof Lateral

Subiculum

white matterTemporal Lobe Entorhinal

Cortex

End of SuperficialLayers of Cortex

Fornix

Geniculate

Dentate

MossyFibers

Gyrus

CA1

SchafferCollaterals CA3

Tail of Caudate

Lateral

Perforant Path

HM

Shaded areashowsHM’sLesion

A

Optic X

Calcarine f.

(Inf

erio

r T

empo

ral s

.)

Perirhinal

Parahippocampal

Piriform

Olfactory bulb

Rec

tus

g.

Infe

rior

Tem

pora

l g.

Occ

ipito

−Tem

pora

l s.

Occ

ipito

−Tem

pora

l g.

Col

late

ral s

.R

hina

l s.

Par

ahip

poca

mpa

l g.

H

(Fus

iform

g.)

fMRI "hot spot"for rememberedwords and pictures

Cut Surfaceof Midbrain

C

H

Orbital gyri

Entorhinal

aphasia

SFG

MFG

IFG

SPL

SMG AG

OC

ITG

MTG

STG

Arcuate Fasciculus

Broca’s Area(Production of Speech)

Auditory Cortex

Wernicke’s Area(Perception of Speech)

POCGPRCG

Fluent aphasia, "word salad"

Non−fluent aphasia, "telegraphic" speech

Radersheidt: Contralateral Neglect

Epilepsy EEG

Mechanisms

K+

Pyramidal neurons also have a "natural tendency" to fire in

contributes to this tendency.

high frequency bursts of action potentials. An intrinsiccapability to generate long duration, calcium action potentials

action potentials in neurons. If these to prevent high frequency bursts ofSeveral systems normally act

epileptic activity can occur.systems are compromised, abnormal,

Original Size of EPSP in dendrite

InhibitoryInterneuron

Compare

Inherited "channelopathies" due to mutations in genes

also contribute to various types of inherited epilepsies.for K, Ca, and Na channels and other membrane proteins

GABA

Long electrotonic length of dendrites normally attenuatesEPSPs so they have relativelylittle effect on firing of APs.

Astrocytes take up extra K andprevent excess depolarization ofneurons. IF K is allowed to accumulate,its equilibrium potential becomes morepositive, bringing resting potentialcloser to threshold.

+

Attenuated Size of EPSP at soma

Astrocyte

Synapse on distal dendrite

Damaged neurons with shortened,truncated dendrites generatelarger EPSPs at the criticalsoma−initial segment region, making the cells hyperexcitable.

_

+

IPSPs normally inhibit neurons and prevent highfrequency firing of action potentials.Many anticonvulsants enhance GABA activity.

axon

Recent research has shown that in epileptic hippocampus

responses to GABA, further contributing to hyperexcitability.some neurons develop abnormal DEPOLARIZING