Structure and Function of the Basal Ganglia Flashcards
EP system
Most movement disorders involve…
Basal ganglia
EP system
components
Basal ganglia Thalamus STN Substantia Nigra Red nucleus
PMC
fun
execution of movement
Discharges prior to onset of muscular activity
Cerebral cortex
List of outputs
(i) Corticospinal tract
(ii) Corollary projections:
(a) Premotor cortex-supplementary motor cortex (SMA)
(b) Somatosensorycortex
(c) Thalamus
(d) Putamen
(e) Cerebellum
Supplementary motor cortex
Fun/lesion
a. Formulation of “motor program”
b. Anterior frontal lobe
c. SMA lesions cause akinesia (paucity of movement) and mutism
Bereitschaftspotential (“readiness potential”)
chars
a. Slow negative potential on EEG
b. Seen over bilateral SMA and PMC in scalp recordings
c. Occurs during early preparation for self-initiated voluntary movement
d. Precedes muscular activity by several hundred milliseconds
Basal ganglia
fun
Basal Ganglia have a major role in filtering motor programs
(1) Optimizes motor programs
Active during both preparation and movement
(2) Integrates sensory and other information to filter motor program
No role in motor decisions or basic parameters of movement
Activated during imaginary motor actions
Cerebellum
fun
(1) Dynamically adjusts motor execution
Adjusts many basic parameters of movement
(i) Velocity, acceleration, deceleration
(ii) Force
Important for automaticity and repetitive movements
Thalamus
fun
(1) Relays information to and from cortex
a. Feedback from basal ganglia
b. Feedback from cerebellum
c. Primary sensory inputs
Brainstem and SC
Motor outputs
Outputs to α- and γ- motor neurons
Outputs to segmental spinal motor circuits
Striatum
Made up of…
Caudate
Putamen
Nucleus accumbens (not imp for mvmnt disorders)
Basal Ganglia
Direct pathway
(i) Cortex: glutaminergic neurons stimulate striatum (ii) Striatum: GABAergic neurons inhibit tonically active GPi & SNpr (pallidum)
(iii) Pallidum: GABAergic neurons reduce inhibition of thalamus
(iv) Thalamus: disinhibited glutaminergic neurons stimulate cortex
Basal ganglia
Indirect pathway
(i) Cortex: glutaminergic neurons stimulate striatum
(ii) Striatum: GABAergic neurons inhibit tonically active GPe
(iii) Gpe: GABAergic neurons reduce inhibition of STN
(iv) STN: glutaminergic neurons stimulate GPi & SNpr (pallidum)
(v) Pallidum: GABAergic neurons inhibit thalamus
(vi) Thalamus: inhibited glutaminergic neurons reduce cortical stimulation
Basal ganglia
Newer concepts of the pathways
(i) The direct pathway encompasses both a “central” positive feedback loop and a sort of “surround inhibition” on competing movement elements by collateral innervation of interneurons
(ii) A “hyperdirect” pathway of cortico-STN connections also contributes to the inhibition
(iii) A “GPe-STN-GPi network” modulates the excitability of the GPi output neurons
Topographic organization of corticostriatal projections
a. Source of cortical afferents predicts the area of densest innervation in the striatum
b. The total area of striatal innervation is an elongated zone which can extend the entire length of the striatum
c. Projections from different areas of cortex converge or diverge in the striatum, depending on their origin
Sensorimotor areas
How are they organized
somatotopically
Sensorimotor areas
loc
(i) Motor and sensory homunculi of the cortex are projected in register onto the lateral putamen
(ii) Feet are dorsal, face is ventral
Oculomotor function
Subserved by…
(i) frontal & supplementary eyefields project to the caudate
(ii) many neurons in the caudate fire during saccadic eye movements
Functional organization of corticostriatal projections
The putamen is the motor nucleus of the striatum
(i) Projections from motor and somatosensory cortex go primarily to the putamen
(ii) Neurons which fire during limb movement are more common in the putamen than caudate, and stimulation of discrete zones of the putamen produces limb movement
The caudate receives dense innervation from the prefrontal cortex
(i) The caudate may play a role in planning, memory-based and psychological aspects of basal ganglia function
Parkinsons disease
Loc of lost neurons/consequence
Parkinson’s disease: more dopamine terminals lost in the putamen than caudate = motor dysfunction
HD
Loc of lost neurons/consequences
Huntington’s disease: caudate degenerates early = cognitive & eye movement abnormalities
Striosomes
Cortical input from layers V & VI
Prefrontal, insular & temporal cortex
Some axons go to dopaminergic neurons in SNc
GABAergic neurons with D1 & D3 receptors are common
High levels of Substance P and Dynorphin
Matrix (matrisomes)
Cortical inputs from layer V and supragranular cortex
Sensorimotor & association cortex
Axons include outputs to direct and indirect pathways
GABAergic neurons with high D2 receptors are common
High levels of Enkephalin
Important for motor functions
Medium spiny neurons
chars
90-95% of striatal neurons
4-5 primary dendrites with abundant spines (post-synaptic boutons)
Axon collaterals which arborize close to the soma
GABAergic, silent at rest
Primary axons projects outside the striatum
Medium spiney neurons
How are the types distinguished
Three types distinguished by dopamine receptor type: D1, D2, D3
Medium spiney neurons
D1 receptors
Substance P and dynorphin
Project to SNr and GPi
Primarily striosomal, but also matrisomal in the direct pathway
Medium spiney neurons
D2 receptors
1) Enkephalins
2) Project to GPe
3) Primarily matrisomal, especially in the indirect pathway
Medium spiney neurons
D3 receptors
Function uncertain
Striatal interneurons
types
1) Cholinergic
1) Large spiney neurons
2) Interact directly with medium spiney output neurons
2) Somatostatinergic
1) Medium aspiney neurons
3) Both somatostatin & acetylcholine markers are denser in the matrix neuropil (matrisomes)
D1 and D2 dopamine receptor families
D1 family: D1 & D5
(a) Dopamine is an excitatory transmitter
(b) Positive coupling to cAMP
D2 family: D2, D3, D4
(a) Dopamine is an inhibitory transmitter
(b) Negative coupling to cAMP
Convergence vs Parallelism
(1) Anatomically, there is convergence with connections from many neurons to fewer neurons
(2) Physiologically, there are many parallel circuits which do not interact
(3) Removing the dopamine generates increasing communication between parallel circuits and creates convergence.
Lesions causing hyperkinetic disorders
(1) Generally interrupt the indirect pathway, causing increased positive feedback to cortex
a. Lesions in the subthalamic nucleus cause hemiballism
b. Huntington’s disease disrupts the connection from the striatum to the lateral globus pallidus
Lesions causing hypokinetic disorders
(1) Loss of dopaminergic input to the striatum in Parkinson’s disease increases activity in the indirect pathway while decreasing activity in the direct pathway, due to the differential effects of D1 and
D2 receptors
Role of basal ganglia
Planning: modeling the motor program
Funneling (convergence) vs parallel processing
Basal ganglia = state feedback
Vs
Cerebellum = dynamic feedback
