Lecture on Thalamus and cortex, Tuesday June 17

Jonathan B. Levitt:
[email protected]
212.650.8539
Key points:
Thalamus as relay and gateway to cerebral cortex
Classification of thalamic nuclei
Links between thalamus and cortex
Classification of cortical areas/lobes
Cellular components of cortex/Basic circuitry
Columnar organization of cortex
 Forebrain (Prosencephalon)

1) Telencephalon
i) cerebral hemispheres
ii) olfactory bulbs
iii) basal nuclei (ganglia)
iv) lateral ventricles

2) Diencephalon (~2% of neuraxis)
i) Epithalamus ­ pineal, habenula, stria medullaris 
(from septal & preoptic nuclei to habenula)
ii) Subthalamus ­ subthalamic nucleus, zona incerta, 
fields of Forel (paths between basal ganglia & thal)
iii) Hypothalamus
iv) Metathalamus ­ LGN & MGN
v) Dorsal thalamus ­ "THE" thalamus
vi) 3rd ventricle
Midbrain­diencephalic junction: nuclei of caudal thalamus 
surround posterior and lateral mesencephalon
LGN, MGN, pulvinar

Caudal diencephalon: habenula (dorsomedial surf of thal: 
convergence of limbic info to rostral midbrain), 3V, 
mammillary bodies

Epithalamus: pineal, habenula, stria medullaris (fibers 
from septal nuclei, lateral preoptic nucleus hypothalamus, 
and anterior thalamic nuclei to the habenula).
Midsagittal view of the cerebral hemisphere
 Midsagittal view showing thalamus in relation to nearby
structures

T
 Dorsal view of brainstem

Int capsule
caudate

3V
thalamus habenula

tectum
Classification of thalamic nuclei
4 main groups
(1) Anterior:
input: mammillary bodies of hypothalamus and
presubiculum of hippocampus
output: cingulate and frontal cortex
Role: memory & emotion?

(2) Medial: mediodorsal nucleus

input: basal ganglia, amygdala, midbrain
Role: memory?
Classification of thalamic nuclei (cont)
(3) Ventral: VA, VL
input: basal ganglia & cerebellum
output: motor cortex
Role: motor
VPL, VPM: somatosensory information to neocortex

(4) Posterior: MGN, LGN, LP, pulvinar

Role: sensory relays,
to auditory, visual, or association cortices
Classification of thalamic nuclei (cont)
(1) Relay (specific) nuclei: e.g. LGN
specific relationship with particular portion of cortex
(2) Association nuclei: no ascending input, project to
association areas of cortex
(3) SubCortically projecting: note special case of Reticular
nucleus: GABAergic, contact other thalamic nuclei rather
than the cortex
(4) Diffuse Cortically projecting (nonspecific) nuclei: e.g.
paraventricular, centromedian on midline, control
cortical arousal, sensory integration?
 Major nuclei of the thalamus
A. Anterior Nuclear Group (mammillary bodies -> cingulate)
1. Anteroventral nucleus (AV) R
2. Anterodorsal nucleus (AD) R
3. Anteromedial nucleus (AM) R

B. Medial Nuclear Group (everywhere claustrum, PAG, SC, midbrain ->PFC)

Dorsomedial nucleus (DM) [or Mediodorsal (MD)]
a. parvicellular part (DMpc) A
b. magnocellular part (DMmc) SC
c. paralaminar part (DMpl) R

C. Midline Nuclear Group (links w/hypothalamus, PAG, striatum, other thal nuclei)
1. Paratenial nucleus DC, SC
2. Paraventricular nucleus DC, SC
3. Reuniens nucleus DC, SC
4. Rhomboidal nucleus DC, SC
 Major nuclei of the thalamus
D. Intralaminar Nuclear Group (arousal: from BG, reticular formation, cortex, SC,
vestib nuclei -> cortex, BG)
1. Centromedian nucleus (CM) SC, DC
2. Parafascicular nucleus (PF) SC, DC
3. Paracentral nucleus SC, DC
4. Central lateral nucleus SC, DC
5. Central medial nucleus SC

E. Lateral Nuclear Group (sensory)

1. Lateral dorsal nucleus (LD) A
2. Lateral posterior nucleus (LP) A
3. Pulvinar (P) A medial, lateral, inferior parts

F. Ventral Nuclear Group (motor: BG, cerebellum -> motor cortex)

1. Ventral anterior nucleus (VA)
a. parvicellular part (VApc) R, SC, DC
b. magnocellular part (VAmc) R, SC
(cont)
 Major nuclei of the thalamus
F. Ventral Nuclear Group
2. Ventral lateral nucleus (VL)
a. oral part (VLo) R
b. caudal part (VLc) R
c. medial part (VLm) R

3. Ventral posterior nucleus (VP) R

a. ventral posterolateral (VPL) R
b. ventral posteromedial (VPM) R
c. ventral posterior inferior (VPI) R

G. Metathalamus
1. Medial geniculate body/nucleus (MGB/MGN) R
a. parvicellular part (MGpc)
b. magnocellular part (MGmc)
2. Lateral geniculate body/nucleus (LGB/LGN) R
a. dorsal part R
b. ventral part SC
 Major nuclei of the thalamus
H. Unclassified thalamic nuclei
1. Submedial nucleus (orbital cortex)
2. Suprageniculate nucleus (from cerebellum)
3. Limitans nucleus (cingulate)

I. Thalamic reticular nucleus (RN) SC

 Inputs/Outputs of the major thalamic nuclei
A. Anterior Nuclear Group: Anteroventral nucleus (AV)
inputs from mammillothalamic tract, fornix
outputs to cingulate gyrus (areas 23, 24, 32), limbic cortex
emotion, memory???

B. Medial Nuclear Group: Dorsomedial nucleus (DM)

inputs from amygdala, substantia nigra, temporal & orbitofrontal cortex,
outputs to cingulate gyrus (areas 23, 24, 32), limbic cortex
strong reciprocal links with frontal lobe (NOT primary motor but premotor and frontal
eye fields)
affective behavior, motivated motor behavior

C. Midline Nuclear Group (less distinct cell groups, hard to distinguish)

inputs from hypothalamus?
outputs to amygdala, cingulate cortex
visceral function
 Inputs/Outputs of the major thalamic nuclei

D. Intralaminar Nuclear Group

inputs from brainstem reticular formation, dentate nucleus, GP, spinal cord
(somatosensory afferents), frontal cortex (areas 4, 6, 8, 9)
outputs to lateral nuclei, putamen, subthalamic nucleus, widespread cortical areas
wakefulness & arousal (“pacemaker”), pain, sensorimotor integration, motor control

E. Lateral Nuclear Group

inputs from / thalamic relay nuclei, tectum, parietal cortex, visual areas
outputs to cingulate cortex, parietal & visual areas
relay sensory signals, sensorimotor integration

F. Ventral Nuclear Group

inputs from striatum, dentate, substantia nigra, (pre)motor cortex, intralaminar and
midline thalamic nuclei / somatosensory periphery
outputs to intralaminar nuclei, frontal cortex / somatosensory cortex
motor control / somatosensory relay
 Inputs/Outputs of the major thalamic nuclei

G. Metathalamus
MGN: inputs from auditory periphery (inferior colliculus), outputs to primary
auditory cortex
LGN: inputs from retina, outputs to primary visual cortex
auditory and visual relays

H. Unclassified thalamic nuclei

I. Thalamic reticular nucleus

inputs from cortex and principal thalamic nuclei
outputs to thalamic nucleus from which it receives inputs
NO outputs to cortex
integrate and gate thalamic transmission to neocortex
Horizontal section at level of corpus callosum

Thalamus
Horizontal section through thalamus - Weil (myelin) stain

Anterior nuclei
Medial nuclei

Lateral nuclei
Pulvinar
 Horizontal section below level of corpus callosum

Anterior nuclei
mediodorsal
Cingulate
lateral
cortex
 Horizontal section further below corpus callosum

anterior
lateral
medial

pulvinar
Horizontal section further below corpus callosum

thalamus

superior colliculus
Nissl-stained coronal section through rhesus
thalamus: identification of nuclei
Nissl-stained coronal section through rhesus
rostral thalamus
Nissl-stained section through rhesus rostral thalamus
(posterior to previous)

LV

3V
Nissl-stained section through rhesus thalamus
(posterior to previous)

RN
SN
Nissl-stained section through rhesus caudal thalamus

pineal
Coronal section at rostral border of thalamus

thalamus

hypothalamus
 Coronal section through thalamus
(just posterior to previous)

Internal thalamus
capsule
hypothalamus

Mammillary
body
 Coronal section through thalamus
(just posterior to previous)

thalamus

subthalamus

Substantia
nigra
 Coronal section through thalamus
(just posterior to previous)

thalamus 3V

Red nucleus
Substantia
pons
nigra
 Coronal section through posterior thalamus
(just posterior to previous)

thalamus

LGN
MGN
midbrain
Evidence for neurochemical subdivisions within
individual thalamic nuclei
Evidence for
neurochemical
subdivisions
within
individual
thalamic nuclei

Gutierrez et al., JCN

 Major thalamic nuclei and their projections

While most cortical areas project back to the thalamic nuclei from which they get
inputs, this is not true of intralaminar or reticular nuclei.
Cortical targets of thalamic projections
Thalamic nuclei
A few fun brain facts (from http://faculty.washington.edu/chudler/facts.html):
• Mass of a large sensory neuron = 10-6 gram
• Number of synapses for a "typical" neuron = 1,000 to 10,000

• Diameter of neuron = 4 micron (granule cell) to 100 micron (motor neuron in cord)

• Diameter of neuron nucleus = 3 to 18 micron

• Length of Giraffe primary afferent axon (from toe to neck) = 15 feet

• Resting potential of squid giant axon = -70 mV

• Conduction velocity of action potential = 0.6-120 m/s (1.2-250 miles/hr)

• % brain utilization of total resting oxygen = 20%; % brain of total body weight (150 pound human) = 2%

• Average number of neurons in the brain = 100 billion

Number of neurons in brain (octopus) = 300 million (from How Animals See, S. Sinclair, 1985)
• Average number of glial cells in brain = 10-50 times the number of neurons

• Number of neocortical neurons (females) = 19.3 billion (Pakkenberg et al. Exp. Gerontology, 38:95-99, 2003 and
Pakkenberg, B. and Gundersen, H.J.G. J. Comp. Neurology, 384:312-320, 1997.)
• Number of neocortical neurons (males) = 22.8 billion (Pakkenberg et al., 1997; 2003)

• Average loss of neocortical neurons = 85,000 per day (~31 million per year) (Pakkenberg et al., 1997; 2003)

• Average loss of neocortical neurons = 1 per second (Pakkenberg et al., 1997; 2003)

• Average number of neocortical glial cells (young adults ) = 39 billion (Pakkenberg et al., 1997; 2003)

• Average number of neocortical glial cells (older adults) =36 billion (Pakkenberg et al., 1997; 2003)

• Length of myelinated nerve fibers in brain = 150,000-180,000 km (Pakkenberg et al., 1997; 2003)

• Number of synapses in cortex = 0.15 quadrillion (Pakkenberg et al., 1997; 2003)

• Difference number of neurons in the right and left hemispheres = 186 million MORE neurons on left side than right
side (Pakkenberg et al., 1997; 2003)
Grey matter: groups of cells,
unmyelinated
White matter: myelinated axons
Gyrus: convolution, outfolding
Sulcus: groove between gyri
Fissure: deeper than a sulcus
The pyramidal cell is the basic
excitatory cell of the neocortex
The pyramidal cell soma - note nucleolus
 Dendrites
• Range from 20 to
2000 µm
• Same intracellular
inclusions as the
somata
• Receive information
from other cells
– Spines on some
Spines: stubby and thin
Spiny and Not Spiny - nonspiny cells are inhibitory
interneurons (local circuit neurons)
Intracortical axons are typically unmyelinated

Myelinated Unmyelinated
Synapses
Lamination of primary visual cortex
Lamination of cerebral cortex
I (molecular): few cells, mostly fibers
from deeper layers (apical dendrites)
II (external granular): small pyramidal
cells
III (external pyramidal): larger
pyramidal cells
IV (internal granular): thalamic input
layer
V (internal pyramidal): subcortical
output layer
Cerebral cortex (~40% brain mass/180g)

I ­ molecular layer: few cells, many horizontal fibers (2 main types)
Axons from opp hemisphere Non­specific thalamic afferents

II – external granular layer: densely packed small pyramidal cells, 
whose axons generally do not leave that area, get input from layer I 
fibers

III – external pyramidal layer: larger cells more loosely packed, also 
with apical dendrites to layer I, basal dendrites to layers III, IV

IV – internal granular layer: small cells, many horizontal fibers from 
specific thalamic afferents; adjacent regions in thalamus project to 
adjacent regions in layer IV

V – internal pyramidal layer: contains giant cells (Betz), give rise to 
longest axons, e.g. motor output to spinal cord, also callosal fibers

external and internal stripes of Baillarger, fiber layers IV and V

VI – multiform layer: feedback projection to thalamus
 A More Detailed Look at
Cortical Lamination
• PN26BA0.JPG
Archicortex: 3 layers hippocampus,
pyriform cortex

Paleocortex: 3 layers
ventral surface of cerebral
hemispheres, parahippocampal gyrus
of medial temporal lobe

Neocortex: “THE” cortex, 6 layers

 Structure of the Human
Neocortex Including Association
Cortices
• PN26021.JPG
Main neurotransmitters in the
neocortex

Glutamate/Aspartate/Kainate: (spine-
bearing neurons) excitatory
neurotransmission

GABA: (smooth dendrites) inhibitory

neurotransmission

Serotonin (5-HT), Dopamine,

Canonical Neocortical Circuitry
• PN26030.JPG
Lateral View of the Human Brain
• PN01121.JPG
Coronal section through the cerebral hemispheres
 Internal Structures of the Brain
Seen in Coronal Section
• PN01162.JPG
Use of
cytoarchitecture
to define cortical
areas
Brodmann’s
definition of cortical
areas
Brodmann’s definition of cortical areas
Classification of cortical areas by myeloarchitecture
Schematic Representation of the
Main Mechanosensory Pathways
• PN09063.JPG
Schematic Representation of the
Main Mechanosensory Pathways
• PN09061.JPG
 General Organization of the
Somatic Sensory System
• PN09011.JPG
Organization of
corticocortical
projections among
different areas of
cerebral cortex
This is just the visual system. Oh my god!...
Maps in the neocortex
Maps in cortex
Somatotopic Order in the Human
Primary Somatic Sensory Cortex
• PN09082.JPG
Changes in the Somatic Sensory
Cortex of an Owl Monkey
Following Amputation of a Digit
• PN25141.JPG
Changes in the Somatic Sensory
Cortex of an Owl Monkey
Following Amputation of a Digit
• PN25142.JPG
Changes in the Somatic Sensory
Cortex of an Owl Monkey
Following Amputation of a Digit
• PN25143.JPG
Functional Expansion of a Cortical Representation by a
Repetitive Behavioral Task

• PN25150.JPG
 Neurons in the Primary Visual
Cortex Respond Selectively to
Oriented Edges
• PN12091.JPG
 Neurons in the Primary Visual
Cortex Respond Selectively to
Oriented Edges
• PN12092.JPG
Kandel et al.
Columnar Organization of Orientation Selectivity in the
Monkey Striate Cortex

• PN12120.JPG
Columnar Organization of Ocular
Dominance
• PN12131.JPG
Columnar Organization of Ocular
Dominance
• PN12132.JPG
Optical Imaging of Functional Domains in the Visual
Cortex
Functional maps on cortex.

Examples of
orientation
maps (top) and
ocular
dominance
maps (bottom)
in V1.

Hubener et al., 1997

1 mm
Zeki et al.
Zeki et al.
Mountcastle VB (1957) Modality and
topographic properties of single
neurons of cat’s somatic sensory
cortex. J. Neurophysiol. 20: 408-434.

Hubel DH & Wiesel TN (1962) Receptive

fields, binocular interaction and
functional architecture in the cat’s
visual cortex. J. Physiol. (Lond) 160:
106-154.