Download Telencephalon

Telencephalon
Endbrain
Telencephalon
+ Amygdala → limbic system
Telencephalon – an extended list of
components
Directional terms – forebrain level
dorsal
superior
caudal
posterior
rostral
anterior
ventral
inferior
Basal ganglia
Telencephalon
Lateral
ventricle
Basal ganglia nomenclature
Corpus Striatum
Caudate Nucleus
Neostriatum
Lenticular Nucleus
Striatum
Putamen
Globus Pallidus
Corpus Amygdaloideum
Paleostriatum
Archistriatum
Pallidum
Lateral surface
of basal ganglia
1. Putamen
2. Tail of caudate
nucleus
3.
Caudatolenti
cular gray
bridge
4. Amygdaloid
body
5. thalamus
Medial surface of basal ganglia
1. head of
caudate nucleus
2. body of
caudate nucelus
3. caudatolenticular
gray bridge
4. putamen
5. tail of
caudate nucleus
6. external segment of
globus pallidus
7. internal segment of
globus pallidus
8. amygdaloid body
9. nucleus accumbens
septi
The Basal Ganglia
Caudate
Putamen
Globus
Pallidus
The Basal Ganglia
Basal ganglia terminology
(Note: the Subthalamic Nucleus and the Substantia Nigra are
functionally, but not anatomically, part of the Basal Ganglia)
Caudate
Putamen
Glob Pall
Subthal Nuc
Sub Nigra
Basal ganglia terminology
Caudate
STRIATUM
Putamen
Glob Pall
Subthal Nuc
Sub Nigra
Basal ganglia terminology
Caudate
Putamen
Glob Pall
Subthal Nuc
Sub Nigra
LENTICULAR
NUCLEUS
Basal ganglia terminology
Caudate
Putamen
Glob Pall
Subthal Nuc
Sub Nigra
CORPUS
STRIATUM
Globus pallidus is divided into external (GPe;
lateral) and internal (GPi; medial) segments
Put
GPe
GPi
Levels of various structures associated with
movement control
Lateral 3D view of basal ganglia & cortex
body → parietal lobe
head → frontal lobe
tail → the temporal lobe
body → parietal lobe
anterior
posterior
head → frontal lobe
tail → the temporal lobe
Lateral 3D view of basal ganglia
Lateral → medial 3D view of basal ganglia
Coronal brain section at the level of
basal ganglia
Put
GPe
GPi
Anterior frontal coronal section
Thalamus is not present → it is more posteriorly located
Head
Caud
Put
GPe
GPi
Tail of caudate
Position of caudate vs thalamus
Origin of CNS subdivisions
Basal ganglia originate from the
telencephalic vesicle
The basal ganglia are derived from the basal
side of the telencephalic vesicle
Lateral
ventricle
Basal ganglia
The basal ganglia are derived from bulges of the
telencephalic vesicle called ganglionic eminences
LGE
LGE
MGE
MGE
Mouse E12.5
Medial GE → pallidum
Lateral GE → striatum
Human 11 wk
Campbell, 2003/ Meyer, 2001
Early development
Late development
As the cerebral cortex grows, it also forces the underlying basal ganglia to assume a C-shape
Estimated time of development of various brain regions
2 mo
6 mo
Modified from Bayer SA et al. Neurotoxicology 14:83–144, 1993
Macroscropic anatomy of major basal ganglia
regions
Striatum (caudate and
putamen)
Lenticular nucleus
(putamen and globus
pallidus)
Subthalamic nucleus
Substantia Nigra
Striatum = caudate + putamen
Telencephalic origin
Follows curvature
telencephalic vesicle
during development
Head (Rostrum) more
voluminous in the human
than the body
Putamen and Globus Pallidus
(Lenticular Nucleus)
From the junction of
diencephalon and
telencephalon
Triangular on coronal
sections
Elongated on axial
sections
Globus Pallidus = pallidum = paleostriatum
Subthalamic Nucleus
Arises from the
diencephalon
Under the thalamus
Biconvex lens shape
White matter
tracts in pallidum
external
capsule lateral
medullary
lamina
medial
medullary
lamina
Substantia Nigra
Mesencephalic origin
Pars compacta and
reticulata
Just beneath
subthalamic nucleus
Flattened ellipsoid
Lies along cerebral
peduncle
Main loop: cortex-basal ganglia-thalamus
Cortex
(+)
Substantia
nigra
(+)
Thalamus
(-)
Basal ganglia
Some basal ganglia neurons mainly receive input from cortex;
others – mainly output to thalamus
Basal ganglia have different input & output components
Input
to
basal
striatum
ganglia
Output
Other basal ganglia structures
Ventral (limbic) striatum
nucleus accumbens septi - reward center;
potential involvement in drug addiction
deep portions of olfactory tubercle
ventromedial portions of the caudate
nucleus and putamen
Nucleus Accumbens
Where the
anterior limb
of the internal
capsule does
not divide the
caudate and
the putamen
Ventral (limbic) striatum - connections
Receives from limbic cortex (hippocampus,
amygdala, entorhinal and perirhinal cortices
(areas 28 and 35), anterior cingulate cortex (area
24), medial orbitofrontal cortex, and widespread
sources within the temporal lobe)
Projects to ventral pallidum
Ventral pallidum
The globus pallidus and
the ventral pallidum are
separated by the anterior
commissure
Striatal neurons
96% - projection neurons (medium spiny
neurons)
Dendrites covered with dendritic spines
Input from cortex to spine heads
Intrinsic basal ganglia input contacts
dendritic shafts (modulates or inhibits
cortical input)
Axon gives rise to dense local collateral
arborization with other spiny neurons
GABA-ergic; also contain substance P,
dynorphin, enkephalin
Silent at rest, activated by cortica inputs
Striatal projection neurons
Total striatal neurons – 100 million
75% - medium spiny neurons
Purves, et al, Neuroscience, 3rd ed.
Striatal projection neurons use GABA and
different neuromodulators
Put
GPe
Put
GPi
GPe
GPi
Afferent different neurons have different
patterns of termination on dendrites and
soma of striatal projection neurons
spine shaft
spine head
Other striatal neurons (4% - interneurons)
Small
GABA-ergic interneurons
Large Cholinergic interneurons
Interneurons provide local surrounding
inhibition
Large cholinergic interneurons are
Tonically Active Neurons (TANS)
function in learning and reward behavior
Convergent inputs
onto a medium spiny
neuron from cortical
neurons, dopaminergic
cells of the substantia
nigra, and local circuit
neurons.
Purves, et al, Neuroscience, 3rd ed.
Striate neurons increase their rate of discharge
just before an impending movement
↓
The activity of these cells may encode the
decision to move toward the target
Marjuana, endocannabinoids & cannabinoid receptors
CB1-R
Purves, et al, Neuroscience, 3rd ed.
THC induces dendritic growth in basal ganglia
Kolb et al., (2006)
Amphetamine induces increased spine
density in basal ganglia
Li et al (2003)
Striatum is composed of matrix &
striosome compartments
Striosome
Matrix
Acetylcholinesterase histochemistry
Enkephalin immunohistochemistry
All tissue outside the striosomes is the matrix compartment
Striosome and
Matrix compartment
AchE
Characteristics of striosome and matrix compartments
Striosomes
Matrix
Acetylcholinesterase Light
staining
Heavy
Cell development
Early
Late
Input
Medial frontal cortex, limbic
cortex, substantia nigra pars
compacta, ventral SNPC
Sensorimotor cortex, SMA,
association cortex, IL
thalamic nuclei, dorsal
SNPC
Output
Substantia nigra pars compacta
Substantia nigra pars
reticulata, globus pallidus
Neurotransmitter
GABA
GABA
Neuromodulators
Neurotensin, dynorphin, substance Somatostatin, enkephalin,
P
substance P
Dopamine receptor
D1
D2
Pallidal neurons
Receive striatal input
Dendrites long, thick, smooth, sparsely
branched
Covered with synaptic boutons (90% striatum,
10% other eg. STN, PPN)
Discoid shaped arborizations that are
perpendicular to striatal axons
GABA-ergic; project to & inhibit thalamus
100 times less numerous than spiny striatal
neurons (convergence of input onto pallidal
neurons from striatal spiny neurons)
Probably help in control of fine and global
movements
Output of basal ganglia – GP & SNpr
Purves, et al, Neuroscience, 3rd ed.
Convergence of striatal neurons onto GP & SNpr
neurons
75 million medium spiny striatal neurons
↓ 100/1
700 000 GP & SNpr neurons
Disinhibitory circuits of basal ganglia
Purves, et al,
Neuroscience,
3rd ed.
Nigral neurons
Same dendrites as pallidal
neurons
No discoidal dendritic
arborization
SN pars compacta - dopamine
SN pars reticulata - GABA
Subthalamic neurons
Dendritic arborizations are intermediate in
number, branch points, and length between striatal
and pallidal neurons
Occasional spines
*Use glutamate (excitatory)
Dendrites can extend outside of the nucleus and
get input from the zona incerta
The relationships of the basal ganglia to the major
components of the motor system
Loop: cortex-striatum-pallidum-thalamus
Cortex
(+)
Striatum
(+)
Thalamus
(-)
(-)
Pallidum
Basal ganglia - summary of connections
Motor Cortex
VL Thalamus
Caud/Putamen
direct pathway
GPi/SNpr
indirect pathway
Subthal Nucleus
GPe
SNpc
Basal ganglia connections
Motor
corte
x
Str
Th
STN
Feedback circuit involving the thalamic
centromedian nucleus
Glutamatergic
thalamostriate fibers
Function - alert the individual; elicit responses that will enable it to evade painful stimuli
Summary of basal ganglia outputs
Somatotopic organization of the basal gangliathalamocortical motor circuit
Kandel, Schwartz, Jessell;
Principles of Neural
Science, 4th ed.
Direct vs indirect pathways
Direct pathway → disinhibition
of thalamic excitation
Indirect pathway →
modulation of direct pathway
(+)
(-)
(-)
(-)
(-)
(+)
Fascilitates movement
Inhibits
movement
SNpc modulates both direct and indirect
pathways
Substantia nigra pars compacta
(SNpc) inhibits the indirect pathway
Substantia nigra pars compacta
(SNpc) promotes direct pathway
Transmitter of SNpc is dopamine –
different effects come from different
dopamine receptors (D1 vs D2)
SNpc →
direct pathway↑
↑
D1
D2
SNpc → indirect pathway↓
↓
Major diseases of basal ganglia
Parkinson’s Disease (parkinsonism)
Huntington’s Disease (chorea, ballism)
Risk factors:
Parkinson
Ebadi, Pfeiffer. Parkinson’s disease, 2005, 5ed.
α-Synuclein & Parkinson
PD pathology - Lewy body
Indirect pathway in Parkinson’s disease
In the indirect pathway there is a
loss of excitation of the GPe by
putamen resulting in a decreased
inhibitory output from GPe to
STN
This decreased inhibitory output
leads to excessive excitatory
output to the GPi, increasing
inhibitory output of GPi to
thalamus and brainstem.
Common Thread Between the Direct and
Indirect Pathways in Parkinson’s Disease
Both the direct and
indirect pathways
lead to increased
inhibitory activity
from GPi to the
thalamus and
brainstem
↑
↓ SNpc → direct pathway ↓
↓ Thalamocortical Circuit
↓ SNpc → indirect pathway↑
↑
Is it Inhibition of the Thalamocortical
Circuit that Causes Parkinson’s?
The inhibition of thalamocortical
and the midbrain projections in
the motor circuit has been
proposed as the primary cause
for the development of
parkinsonian motor signs and
hypokinetic features of PD
⇐
Cardinal Features of
PD
Tremor (at rest)
Rigidity
Bradykinesia
Shuffling Gait
Balance Problems
Basal ganglia function in PD
↑
↑
Sites of surgical intervention in Parkinson disease
Subthalamic nucleus lesion
GPI lesion
Kandel, Schwartz, Jessell;
Principles of Neural
Science, 4th ed.
Transplantation of human mesencephalic
tissue in human Parkinson’s disease
Reason – enriched in dopaminergic neurons
Source – human embryos (6-9 GW) from abortions
Start – 1987; until 2005 ~350 have been transplanted
Main targets
Transplanted neurons survive and connect to other neurons in the
brain of patients
Brain integrates transplanted neurons
Transplants achieve medical improvement
Disadvantages
Non-homogenous cellular population→ variable response
Postoperative dyskinesias in 20-50% of the patients
PET scan shows take-up of 18F-dopa in striatum 2 years
after bilateral implantation of mesencephalic cells in
caudate and putamen of a Parkinson’s disease patient.
Brooks, NeuroRx, Vol. 1, 482–491, October 2004
Huntington’s DiseaseChorea/Ballism
Atrophy of striatum
Huntington’s disease – mostly medium spiny
neurons are damaged
Normal
HD
Large neurons are relatively spared
Basal ganglia function in HD
Normal
HD
↑
↑
↓
↓ Striatum → direct pathway ↓
↓ Striatum → indirect pathway ↓↓
↑ Thalamocortical Circuit
HD – hyperkinetic disorder
Chorea (G. choros, “dance”)
consists of a sequence of rapid,
jerky, somewhat agile and
flowing movements involving
mainly the hands and feet, the
tongue, and facial muscles.
Disinhibition of thalamus
(=excitation) → involuntary
movements
Summary of PD & HD pathophysiology
Parkinson
Normal
Normal
Huntington
Cortex
Cortex
(+)
(+)
(+)
(+)
Thalamus
Thalamus
SN
SN
(-)
(-)
Basal ganglia
Basal ganglia
Hypokinetic
Hyperkinetic
Blood supply of basal ganglia
Striatum → penetrating branches of the anterior and middle cerebral arteries
termed the lenticulostriate arteries
Pallidum → anterior choroidal artery (internal carotid artery)
Intracerebral hemorrhage
Vv. profundae cerebri
Drainage of vv. profundae cerebri
Anastomoses between deep & superficial cerebral veins
Basal ganglia loops – motor & non-motor functions
Functions of basal ganglia loops
Motor loop - automatic execution of a learned
motor plan; preparation for movement
Oculomotor loop - voluntary saccadiac eye
movements
Prefrontal loop - planning of motor activity and
determining the direction of movement;
cognitive function and tasks that require spatial
memory
Limbic loop - emotional and motivational
aspects of movement, manifested as various
facial expressions or other body movements
Motor control integration