Basal Ganglia + Cerebellum Flashcards
Basal Ganglia
Influence movement initiation, selection, & scaling
Cerebellum
Drive coordination, timing, postural reflexes, & adjustments
4 structures of basal ganglia
- Striatum
- Globus Pallidus
- Substantia Nigra
- Subthalamic Nucelus
basal ganglia function
- Procedural Learning
-goal-directed behaviors
- habitual behaviors
- motor chunking - 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
Striatum
“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%)
Medium Spiny Neurons (MSNs)
Inputs: spiny, dendritic inputs, from all corticies except primary sensory
Outputs: negligible spontaneous activity; gabaergic projections
Classes: two spatially intermingled classes (D1, D2)
D1 Spiny Neurons
Direct Pathway
Receptor Types: Dopamine: D1R
Adenosine: A1R
Neuropeptides:
Substance P
Dynophorin
Projects to:
GPi + SNr
(basal ganglia output)
D2 Spiny Neurons
indirect pathway
receptor types:
Dopamine: D2R
Adenosine: A2AR
Neuropeptides:
Enkephalin
projects to:
GPe
(basal ganglia intrinisic)
Globus Pallidus
primarly refers to dorsal
Primarily constitutively firing gabaergic projection neurons
Two segments:
– Globus Pallidus externus (GPe)
– Globus Pallidus internus (GPi)
GPe (lateral pallidum)
Striatal afferents from D2-MSNs along indirect pathway
Efferents to GPi, STN and SNr
GPi (medial pallidum)
Striatal afferents from D1-MSNs along direct pathway
Efferents to thalamus constitute primary basal ganglia outputs
Subthalamic Nuc
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
Substantia Nigra
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
Basic Connectivity
Gating & Selection
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
Negative Gating
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
Action Selection
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
Dopamine
from SNc
Overview
Tonic striatal dopamine relevant to activity level
Phasic striatal dopamine relevant to reward & learning
Parkinson’s Disease Symptoms
Bradykinesia & Akinesia: suppression of movement, or inability to initiate movement
Rigidity & Tremor: disruption of action selection mechanism
Apathy, Depression, Anxiety: same deal, other loops
Parkinson’s Disease Treatments
Levodopa (L-DOPA)
Restores tonic dopamine
Less effective for phasic
Over time, dyskinesias
Deep Brain Stimulation (DBS)
STN or GPi
Over-activate SNr/GPi ?
Cerebellum function writ large
Drive coordination, timing, postural reflexes, & adjustments
3 Lobes of Cerebellum
anterior
posterior
flocculonodular
Cerebellar Nuclei
Dentate, Interposed (Eboliform/Globose), Fastigial
Cerebellar Zones
lateral, medial (vermis/ intermediate)
anatomical cerebellar nuclei
dentate, interposed (eboliform/globose) fastigial
Cerebellar Function
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
Vestibulocerebellum
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
spinocerebellum
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
Cerebrocerebellum
Lateral Hemispheres
Newest region of cerebellum: very large in humans
Inputs: indirect, non-sensory, association corticies
Outputs: dentate nucleus, to largely non-motor corticies
Components of cerebellar microcircuit
Purkinje Cells
Parallel Fibers
Climbing Fibers
Purkinje Cells
Stacked, fan-shaped dendritic arbors
Gaba-ergic projections to deep cerebellar nuclei
Parallel Fibers
(from granule cells)
substantial convergence/divergence onto each purkinje cell (~100k syns!)
Climbing Fibers
(from inferior olive)
only one CF per purkinje cell; minimal divergence (a few)
Results of cerebellar dysfunction?
uncoordinated movements
ataxia
full cerebellar diagram 1
full cerebellar diagram 2
Dopamine Rate Model
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
