Cortex

Neu 257 – Winter 2011H.J. Karten, M. Martone, A. Huberman

What Is The Cortex That We May Know It?

Sherrington: The Cortex Is the Highest Center for Distance Senses

Comparative Neuroanatomy

Source: Comparative Mammalian Brain Collection

The complexity of sulci increased throughout evolution

FIGURE 10 The neural plate is a spoon-shaped region of ectoderm (neural ectoderm) that forms the CNS. Ectoderm that lies outside the neural plate is called somatic ectoderm. The neural plate is polarized (the rostral end is wider than the caudal end), bilaterally symmetrical (divided by the midline neural groove), and regionalized (the rostral half forms the brain, and the caudal half forms the spinal cord). The neural crest lies along the junction between somatic and neural ectoderm, and a series of placodes develops as "islands" within the somatic ectoderm. The neural crest and placodes generate neurons of the PNS. The approximate location of future major brain divisions in the neural plate is shown in color on the left. The same color scheme is used in Figs. 2.11 and 2.12. Refer to Swanson (1992).

•FIGURE 12 Formation and subdivision of the neural tube. (A) The brain region of the early neural tube develops three swellings: forebrain, midbrain, and hindbrain vesicles. The hindbrain vesicle develops a series of transverse swellings called rhombomeres. (B) As neurulation continues, the forebrain vesicle differentiates into right and left endbrain (cerebral hemisphere) vesicles and a medial interbrain vesicle; the hindbrain vesicle differentiates vaguely into pontine and medullary regions. The endbrain vesicle further divides into the cerebral cortex (including the olfactory bulb) and cerebral nuclei (basal ganglia); the interbrain vesicle divides into the thalamus and hypothalamus; the midbrain vesicle divides into the tectum and tegmentum; and the hindbrain divides into the rhombic lip, alar plate, and basal plate (tegmentum). Controversy exists about whether the pretectal region (sometimes called the synencephalon) is part of the interbrain or midbrain. At this stage of development, the major components of the adult ventricular system can be seen in the lumen of the neural tube. Refer to Swanson (1992) and Alvarez-Bolado and Swanson (1996).

Components of the Forebrain:• Forebrain = Prosencephalon

– Diencephalon– Retina– Telencephalon

• Cortex (multiple categories – olfactory, “archicortex”, “paleocortex”, “neocortex”)

• Basal Ganglia• Amygdala

– ?Olfactory bulb?

Development

• FIGURE 14 Major divisions of the adult CNS are derived from the regionalization of the neural plate and neural tube illustrated in Figs. 2.10–2.12. Modified from Swanson (1992).

Major SulciMain sulci are formed early in developmentFissures are really deep sulci

Typically continuous sulci•Interhemispheric fissure•Sylvian fissure•Parieto-occipital fissure •Collateral sulcus•Central sulcus•Calcarine Sulcus

Typically discontinuous sulci•Superior frontal sulcus•Inferior frontal sulcus•Postcentral sulcus•Intraparietal sulcus•Superior temporal sulcus•Inferior temporal sulcus•Cingulate sulcus•Precentral sulcus

Other minor sulci are much less reliable

Source: Ono, 1990

Longitudinal Fissure-interhemispheric fissure-very deep (down to corpus callosum)-divides brain into 2 hemispheres

Medial Frontal-superior frontal gyrus continues on medial side-frontal pole (gray) and orbital gyrus (green) also shown

Cytoarchitecture

•Laminar (layered) structure

•Main cell types: pyramidal neurons (glutamate), stellate cells (glutamate), many classes of inhibitory interneurons, e.g., chandelier cells, double bouquet cells.

Mouse Slide Overview

Mouse Sagittal: Nissl+Myelin

Detail of Entorhinal-Hippocampal Area

Proteomics: Tyrosine Hydroxylase

TyOH Axons in Frontal Cortex of Mouse: 22X

Terminological Nonsense & Evolutionary Misunderstanding

• Neocortex• majority of what we call cortex in humans• e.g., motor, sensory, association cortex

• 6 layered cortex = isocortex (during development passed through a 6 layered phase) – (TOTAL FANTASY!)

• Paleocortex• 2-5 layered

• e.g., pyriform (olfactory) cortex

• Archicortex• 3 layered

• Hippocampus, subiculum

Allocortex (heterocortex)

Brodmann and Cortical Development

• Paleocortex, Archicortex, & Neocortex• Mythology of Scala Naturae

• “Homogenetic and Heterogenetic Cortex”

• “Telencephalization of brainstem functions” – Hughlings Jackson

Cortical Layers

I. Molecular layer - mostly neuropil

II. External granular layer - stellate cells, small pyramidal neurons

III. External pyramidal layer- small pyramidal cells

IV. Internal granular layer - stellate cells

V. Internal pyramidal layer - large pyramidal cells

VI. Multiform layer - multiple cell types

Cortical Layers

Infragranular layers

Supragranular layers

Cortical Lamination Patterns Differ Across Regions

Granular vs agranular cortex

•Refers to a predominance of large pyramidal neurons (e.g., motor cortex) vs small stellate cells (primary sensory cortex)

Pattern of lamination in V1/V2

Brodmann’s Areas

Brodmann (1909):

•Based on cytoarchitectonics: study of differences in cortical layers between areas•Most common delineation of cortical areas•More recent schemes subdivide Brodmann’s areas into many smaller regions•Monkey and human Brodmann’s areas not necessarily homologous

Cortical lamination patterns differ across species

Human Primary Somatosensory Cortex

Parietal Cortex, Giraffe

Platypus Primary Somatosensory Cortex

From: DeFelipe et al., J. Neurocytology, 31: 299, 2002

The Pyramidal Cell•One of several cell types of the cerebral cortex

•Participates in cortico-cortical (layers 2 and 3) and subcortical projections

•Apical vs basal dendrites, both are covered in dendritic spines

•Differ in size across layers and regions (10-100µm soma)

•Largest pyramidal cells “Betz Cells” in primary motor cortex

ConnectionsInputs:

-thalamus

-chemically coded nuclei

-serotonin

-neurepinephrine

-acetylcholine

-dopamine

Outputs:

-thalamus

-Striatum (Caudate-Putamen)

-brainstem, spinal cord

III

III

V

VI

ChAT Staining

Motor cortex

Primary sensory cortex

III

III

VVI

IV

Adapted from Paxinos, G. The Rat Nervous System, 1995

Basic (very) Cortical Circuit

psych.colorado.edu/users/spencer/ psyc2022/CTXconnect.html

Inputs:

•Specific thalamic inputs: layer 4

•Association, non-specific thalamic nuclei: broader distribution

•Chemically coded nuclei: different laminar pattern depending on neurotransmitter, region and species

Outputs:

Layer 2: association fibers

Layer 3: callosal fibers

Layer 5: striatum (5a), brainstem and spinal cord (5b)

Layer 6: thalamus

Commissural Fibers

• Corpus Callosum - connect hemispheres• Anterior Commissure - inferior and middle temporal gyri, olfactory areas• Posterior Commissure - preoptic nuclei (vision)

Association Fibers (Lateral Surface)

1. Superior longitudinal fasciculus2. Inferior occipitotemporal fasciculus3. Uncinate fasciculus4. Perpendicular occipital fasciculus

Fibers of Cerebral White Matter (Coronal Section)

1. Corpus callosum2. Internal capsule3. Superior occipitofrontal fasciculus4. Superior longitudinal fasciculus5. Inferior occipitofrontal fasciculus6. Cingulum7. Uncinate fasciculus8. Inferior longitudinal fasciculus

Cortical Localization

• Lamination of cortex recognized in late 19th century

• Regional Localization recognized consequent to clinical studies of loss of function

• “German School” of descriptive anatomy

• Cytoarchitecture and cortical regions – complex patterns in different zones

Konstantin Brodmann and Cortical Areas

• How do different cortical regions differ from each other?

• Do they differ in phylogeny?• Interrelationship of development and laminar

development• Functional localization associated with differing

cytoarchitecture• Lashley and cortical equivalence – Mass Action• Rose and Woolsey and revival of cortical

localization

Functional Divisions: highly simplified viewPrimary SensoryPrimary Sensory: Receives input from specific thalamic sensory relay

nucleus (except olfactory)

Primary MotorPrimary Motor: Gives rise to direct projection to motor neurons in brainstem and spinal cord

Unimodal Association AreasUnimodal Association Areas: Adjacent to primary areas for that modality; receive projections from primary sensory/motor cortex but only concerned with a single modality

Polymodal Association AreasPolymodal Association Areas: No longer concerned necessarily with a single modality; respond to complex stimuli

From: Bear, Connors and Paradiso, Neuroscience: Exploring the Brain, 2000

Functional Parcellation of Monkey Brain

Felleman and Van Essen’s Parcellation of Macaque Brain

Obtained from: www.hms.harvard.edu/.../bornlab/ lab/figures/FVE_map.html

Primary Motor and Premotor Areas

Cortical Maps

•Sensory and motor space is mapped onto the cerebral cortex

•Representation of space isn’t equal

Other Sensory “-topies”Touch:

Somatotopy

Servos et al., 1998red = wrist; orange = shoulder

Audition: Tonotopy

cochlea

Sylvian fissure

temporal lobe

Movie: tonotopy.mpeghttp://cogsci.ucsd.edu/~sereno/downsweep2.mpg

Source: Marty Sereno’s web page

Cortical Columns

•Work of Vernon Mountcastle, Hubel & Wiesel and others

•Most well defined in sensory cortices

•Originally functional concept, but anatomical correlates as well

•2-500 µm in diameter

•Similar in size across species?: basic functional unit of the cortex?

Fate mapping:Cell birthdatesLocus of originMigration during embryogenesis: local and long rangeComplex morphogenesis: e.g. complex laminated structuresEstablishment of axonal and dendritic connectionsEstablishment of transmitter/receptor/modulator phenotypesEmergence of functionsModification of synaptic properties during developmentMaturation, learning and plasticity

• FIGURE 10 Development of the cerebral cortex. The ventricular zone (VZ) contains the progenitors of neurons and glia. The first neurons to be generated establish the preplate (PP); their axons, as well as ingrowing axons from the thalamus, establish the intermediate zone (IZ). The subsequently generated neurons of cortical layers II–VI establish the cortical plate (CP), which splits the preplate into the marginal zone (MZ), or future layer I, and the subplate (SP), a transient population of neurons. After the completion of neuronal migration and differentiation, six cortical layers are visible overlying the white matter (WM) and the subplate has largely disappeared. Neural precursors in the subventricular zone (SVZ) continue to generate neurons that migrate rostrally into the olfactory bulb, even during postnatal life.

Cell Migration

Inside-Out Migration

• To and fro migration of single cells in early cortical development

• Initially believed that layers were formed in sequential order from outside inwards

• Angevine and Sidman showed “Inside-Out”

• Tangential migration• Are there Neuromeres in the

Prosencephalon?

Cytoarchitecture

•Laminar (layered) structure

•Main cell types: pyramidal neurons (glutamate), stellate cells (glutamate), many classes of inhibitory interneurons, e.g., chandelier cells, double bouquet cells.

Visual Cortex

Properties of Cortex

•Laminar populations (www.brainmaps.org)

•Specific Afferentation and Efferentation

•Differential morphology and molecular properties

•Radial/columnar organization

•Recurrent loops

•Re-entrants

Do All Cortical Areas Do The Same Thing?

•A simplified model of the cortex postulates that all areas have a similar Modulation Transfer Function

•Solve one cortical area mechanism of processing, and --- SHAZAM! You solve them all.

•Oh, REALLY? Is the fundamental hypothesis valid?

The Radial Hypothesis: Columns

The New Cytoarchitectonics

• Mountcastle; Hubel and Wiesel• Electrophysiological studies• Revival of Cajal, Brodmann and others• Is there a common MTF for all cortical

regions – 1890’s, 1930’s, 1990’s-present• Regional and laminar specialization –

vision, somatic sensation, audition, motor• Allen Institute and regional cortical gene

expression.

The Radial Hypothesis Revisited I.

•The concept of columns and modules proved of great heuristic value in physiolgical investigation of the mammalian cortex. (Lorente de No, Mountcastle, Hubel & Wiesel)•Rakic postulated a radial unit hypothesis to explain the development of columns and modules•However, the morphological bases and evolutionary origins of the column and module in the forebrain were unknown.

Evolutionary origins: When did specific cell types first appear? When did specific circuits first appear? When did specific transmitters first appear?When did complex “higher” functions first emerge?

What are the common properties in the CNS of vertebrates?