Basal Ganglia + Cerebellum

Question 1

Basal Ganglia

Answer 1

Influence movement initiation, selection, & scaling

Question 2

Cerebellum

Answer 2

Drive coordination, timing, postural reflexes, & adjustments

Question 3

4 structures of basal ganglia

Answer 3

1. Striatum
2. Globus Pallidus
3. Substantia Nigra
4. Subthalamic Nucelus

Question 4

basal ganglia function

Answer 4

1. Procedural Learning
   -goal-directed behaviors
   - habitual behaviors
   - motor chunking
2. Behavior Modulation
   -movement
   – selects particular movement
   – triggers initiation/termination
   – scales amplitude/speed/force
   - motivation
   – drives ideation/cognitive focus
   – magnifies impulses/apathies/obsesions/compulstions
   – w/ amygdala and nucleus accumbens – addiction/emot behavior

Question 5

Striatum

Answer 5

“that which is striped”
striations are axon bundles. coronally presented as holes
2 nuclei:
1. caudate
2. Putamen

Interneurons (~5%):
– a few small gabaergic classes
– large, cholinergic, tonically active neurons (TANs)
Medium Spiny Neurons (~95%)

Question 6

Medium Spiny Neurons (MSNs)

Answer 6

Inputs: spiny, dendritic inputs, from all corticies except primary sensory
Outputs: negligible spontaneous activity; gabaergic projections
Classes: two spatially intermingled classes (D1, D2)

Question 7

D1 Spiny Neurons

Answer 7

Direct Pathway
Receptor Types: Dopamine: D1R
Adenosine: A1R

Neuropeptides:
Substance P
Dynophorin

Projects to:
GPi + SNr
(basal ganglia output)

Question 8

D2 Spiny Neurons

Answer 8

indirect pathway

receptor types:
Dopamine: D2R
Adenosine: A2AR

Neuropeptides:
Enkephalin

projects to:
GPe
(basal ganglia intrinisic)

Question 9

Globus Pallidus

Answer 9

primarly refers to dorsal

Primarily constitutively firing gabaergic projection neurons
Two segments:
– Globus Pallidus externus (GPe)
– Globus Pallidus internus (GPi)

Question 10

GPe (lateral pallidum)

Answer 10

Striatal afferents from D2-MSNs along indirect pathway
Efferents to GPi, STN and SNr

Question 11

GPi (medial pallidum)

Answer 11

Striatal afferents from D1-MSNs along direct pathway
Efferents to thalamus constitute primary basal ganglia outputs

Question 12

Subthalamic Nuc

Answer 12

Only basal ganglia structure with glutamatergic efferents
Considered intrinsic structure
– branch of indirect pathway
* afferents from GPe
* efferents to GPi & SNr:
– reciprocal efferents to GPe yield negative feedback, e.g., enable pacemaker
Recently shown to receive substantial, largely cortical input: hyperdirect pathway

Question 13

Substantia Nigra

Answer 13

Two Parts: SNr & SNc
Substantia Nigra pars reticulata
Similar to GPi in terms of: inputs, rates, outputs, & transmitter
Substantia Nigra pars compacta
Produces dopamine that it projects into striatum

Question 14

Basic Connectivity

Answer 14

Question 15

Gating & Selection

Answer 15

BG selects & gates actions (et al.)
Efferents are tonically active, inhibiting thalamus & movement
When a BG output is suppressed, its thalamic target is released to drive excitation into cortex

Question 16

Negative Gating

Answer 16

Direct Pathway — Facilitation
— D1 firing disinhibits target loop
— Go: action via focal disinhibition

Indirect Pathway — Suppression
— D2 firing over-inhibits target loop
— Stop: inaction via focal inhibition

Question 17

Action Selection

Answer 17

Direct
— Focal Facilitation
— D1 firing disinhibits target loop

Indirect
— Diffuse Suppression
— D2 firing inhibits all loops
Coactivation selects target action via center-surround mechanism Propagates downstream

Question 18

Dopamine

Answer 18

from SNc

Overview
Tonic striatal dopamine relevant to activity level
Phasic striatal dopamine relevant to reward & learning

Question 19

Parkinson’s Disease Symptoms

Answer 19

Bradykinesia & Akinesia: suppression of movement, or inability to initiate movement
Rigidity & Tremor: disruption of action selection mechanism
Apathy, Depression, Anxiety: same deal, other loops

Question 20

Parkinson’s Disease Treatments

Answer 20

Levodopa (L-DOPA)
Restores tonic dopamine
Less effective for phasic
Over time, dyskinesias
Deep Brain Stimulation (DBS)
STN or GPi
Over-activate SNr/GPi ?

Question 21

Cerebellum function writ large

Answer 21

Drive coordination, timing, postural reflexes, & adjustments

Question 22

Answer 22

Question 23

3 Lobes of Cerebellum

Answer 23

anterior
posterior
flocculonodular

Question 24

Cerebellar Nuclei

Answer 24

Dentate, Interposed (Eboliform/Globose), Fastigial

Question 25

Cerebellar Zones

Answer 25

lateral, medial (vermis/ intermediate)

Question 26

anatomical cerebellar nuclei

Answer 26

dentate, interposed (eboliform/globose) fastigial

Question 27

Cerebellar Function

Answer 27

Computation 70-80% of human neurons Independent, identical circuits repeated throughout Thought to perform roughly the same computation in all domains: coordinate, time, smooth Behavioral Tuning Muscle actions Coordination Motor timing Smooth moves Involved in other domains, but the full effects remain unclear Executive: verbal fluency, working memory, planning Personality / Affect: focus, attention, impulsivity

Question 28

Vestibulocerebellum

Answer 28

Vestibulocerebellum Flocculonodular Lobe Oldest region of cerebellum: center nodulus flanked by 2 flocculi Coordinate balance & oculomotor control Inputs: vestibular, visual, & neck proprioceptive Outputs: brain stem & fastigial nucleus into spine & motor cortex

Question 29

spinocerebellum

Answer 29

Vermis & Intermediate Zones Coordinates motor control via somatotopic mapping Inputs: broadly proprioceptive … but also vestibulary, visual, auditory, & somatosensory Outputs: fastigial & interposed* nuclei, to spine & motor cortex

Question 30

Cerebrocerebellum

Answer 30

Lateral Hemispheres Newest region of cerebellum: very large in humans Inputs: indirect, non-sensory, association corticies Outputs: dentate nucleus, to largely non-motor corticies

Question 31

Components of cerebellar microcircuit

Answer 31

Purkinje Cells Parallel Fibers Climbing Fibers

Question 32

Purkinje Cells

Answer 32

Stacked, fan-shaped dendritic arbors Gaba-ergic projections to deep cerebellar nuclei

Question 33

Parallel Fibers

Answer 33

(from granule cells) substantial convergence/divergence onto each purkinje cell (~100k syns!)

Question 34

Climbing Fibers

Answer 34

(from inferior olive) only one CF per purkinje cell; minimal divergence (a few)

Question 35

Results of cerebellar dysfunction?

Answer 35

uncoordinated movements ataxia

Question 36

full cerebellar diagram 1

Answer 36

Question 37

full cerebellar diagram 2

Answer 37

Question 38

Dopamine Rate Model

Answer 38

D1-MSNs: dopamine increases rate, facilitating movement D2-MSNs: dopamine decreases rate, facilitating movement Loss of Dopamine D1-MSNs: loss decreases rate, suppressing movement D2-MSNs: loss increases rate, suppressing movement