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Basal ganglia Flashcards

1
Q

What is the basal ganglia

A

An extrapyramidal, subcortical system for the selection of internally generated, goal-driven motor programmes

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2
Q

Summary of unctions of basal ganglia- competition

A

Solves a competing input selection problem- plans, motivations and context

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3
Q

Summary of functions of basal ganglia- selection

A

Select goal, select actions to promote goal, seelct movements in response to salient stimuli

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4
Q

Summary of functions of basal ganglia- reinforcement learning

A

Learn outcome of actions and their cues, to adapt behaviour to achieve appropriate and efficient responses to the environment

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5
Q

What are the 4 components of the basal ganglia

A

Striatum, globus pallidus, subthalamic nucleus, substantia nigra

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6
Q

What is the striatum split into

A

Caudate, putamen (split by the internal capsule)

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7
Q

What is the globus pallidus split into

A

External (GPe), internal (GPi)

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8
Q

What is the substantia nigra split into

A

Pars compacta (SNc), pars reticulata (SNr)

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9
Q

How does info from the cortex first enter the basal ganglia

A

Cortex -> Striatum

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10
Q

What neurons in the striatum receive most of the afferent input from the cortex

A

Striatal medium spiny neurons- the principal neuron of the striatum

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11
Q

What is firing of striatal medium spiny neurons correlated with

A

Cues for movement or intended movement, not movement itself

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12
Q

What neurotransmitter identity are striatal medium spiny neurons

A

GABAergic

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13
Q

What are the 2 types striatal medium spiny neurons

A

D1- have dopamine D1 receptors

D2- have dopamine D2 receptors

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14
Q

What do D1 striatal medium spiny neurons express

A

Substance P and dynorphin opioid

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15
Q

What expression do D2 striatal medium spiny neurons have

A

Express enkephalin opioid, have A2A receptors

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16
Q

What does it mean to say the basal ganglia is an extrapyramidal system

A

The tracts of the basal ganglia don’t pass directly through the pyramids of the medulla oblongata aka don’t directly execute movement

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17
Q

Where does the striatum output to

A

Substantia nigra pars reticulata (SNr)/internal globus pallidus (GPi) and external globus pallidus (GPe)

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18
Q

What are the output nuclei of the basal ganglia

A

Substantia nigra pars reticulata (SNr) and internal globus pallidus (GPi)

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19
Q

What is the neurotrasmitter identity of output from the basal ganglia

A

GABAergic neurons

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20
Q

What are the 2 output pathways of the basal ganglia

A

‘ASCENDING’- to VLo/VA

‘DESCENDING’- to upper brainstem eg SC, RF, PPN

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21
Q

By what principle does the basal ganglia modulate the thalamocortical relay

A

Principle of disinhibition

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22
Q

How do striatal neurons to SNr/GPi disinhibit the thalamocortical relay

A

Normally, SNr/GPi cells fire tonically and inhibit the thalamus
Striatal stimulation inhibits the SNr/Gpi, disinhibiting activity in thalamocortical relay neurons

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23
Q

What are the 2 pathways through the basal ganglia

A

DIRECT- striatum->SNr/GPi

INDIRECT- striatum-> Gpe->STN->SNr/GPi

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24
Q

What is the organsation of direct/indirect pathway projections in the striatum

A

Direct/indirect pathway projections are intermingled within the striatum

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25
What output does the substantia nigra pars compacta (SNc) do
Ascending dopamine input to the striatum
26
What is the result of striatal excitation in the DIRECT PATHWAY
Striatum inhibits SNr/GPi, reduced GPi inhibition of thalamus Facilitates movement
27
What is the result of striatal excitation in the INDIRECT PATHWAY
Striatum inhibits GPe, reduced GPe inhibition of STN Excitation in STN excites the GPi, increasing its inhibition of the thalamus Inhibits movement
28
Which of the direct vs indirect pathways facilitates vs inhibits movement
DIRECT PATHWAY- faciliates movement | INDIRECT PATHWAY- inhibits movement
29
How do D1 and D2 receptors segregate in the direct vs indirect pathway
Direct pathway- D1 receptors | Indirect pathway- D2 receptors
30
What is the effect of dopamine on the direct pathway
D1 DA receptors on direct striatal projections FACILITATE the pathway, facilitating movement
31
What is the effect of dopamine on the indirect pathway
D2 DA indirect striatal projections INHIBIT the pathway, facilitating movement
32
What effect does dopamine from SNc have on the direct and indirect pathway
FACILITATES MOVEMENT IN BOTH PATHWAYS | Facilitates the direct pathway, inhibits the indirect pathway
33
List some examples of basal ganglia diseases
Parkinsons', drug-induced Parkinsons, Huntingsons, Tourettes
34
OVERALL symptoms of basal ganglia diseas
Deficiency of movement, involuntary movements
35
Symptoms of basal ganglia disease- deficiency of movement examples
Akinesia, bradykinesia
36
Symptoms of basal ganglia disease- involuntary movements examples
Tremor at rest, dystonias, chorea, tics, dyskinesias
37
Primary motor symptoms of Parkinsons
Akinesia, tremor at rest, rigidity, postural instability (TRAP)
38
Non-motor dysfunction in Parkinsons
Problems with sleep behaviour, depression, cognition, pain, dementia, bowels
39
What neuronal changes underlie Parkinsons
Progressive loss of SNc DA neurons (DA facilitates movement) | Proteinaceous aggregations
40
What are proteinaceous aggregations in Parkinsons
Lewy bodies- intraneuronal cytoplasmic inclusions | Major components are a-synuclein and ubiquitin
41
How does the intrinsic physiology of SNc neurons promote their vulnerability to Parkinsons
Very highly arborised means high metabolic demand | Oxidative stress, neuroinflammation, protein misfolding and accumulation
42
Environment contributions to Parkinsons
Neuroinflammation, pesticides + genetics, toxin exposure (MPTP toxicity)
43
What causes MPTP toxicity
Selective entry of MPP+ into DA neurons leads to downstream increase of ROS (reactive oxygen species) via DA dumping, causing selective death
44
What key drug treatment is used for Parkinsons
L-DOPA (precursor of dopamine) PLUS an inhibitor of peripheral decarboxylase Increased dopamine production
45
How is L-DOPA problem as a treatment for Parkinsons
On/off effects, gait freezing, LDOPA induced dyskinesia typically occur within 5-10 years of LDOPA therapy
46
Alternative Parkinsons therapy options to LDOPA
DA agonists, gene therapy, transplans, DBS
47
How does deep brain stimulation work
Stimulating electrode implanted during surgery into basal ganglia nuclei eg STN, GP High frequency stimulation
48
Symptoms of Huntington's chorea
Usually hyperkinetic | Chorea, dystonia, rigidity and cognitive decline
49
What changes occur to brain structure in Huntington's chorea
Striatal atrophy-loss of caudate nucleus GABAergic medium spiny neurons (particularly D2) Cortical atrophy
50
Underlying causes of Huntington's disease
Genetics, 'codon-repeat disease' that encodes consecutive polyglutamines from huntingtin gene (HTT), HTT protein aggregates
51
How do brain structure changes in Huntington's cause its hyperkinetic phenotype
D2 neurons especially affected, meaning the direct pathway dominates the indirect pathway, causing decreased inhibition of the thalamus
52
Treatments for Huntingtons
Antidopaminergics, tetrabenazine, neuroleptics, benzodiazepines
53
Where does the thalamus project to
The frontal lobe, the same areas that provided the basal ganglia with input
54
What is the neurotransmitter identity of STN output
Glutamatergic
55
What are the maps in the basal ganglia like
Topographical maps of the area of cerebral cortex they receive input from Some of these cortex areas receive input from the other lobes
56
Examples of basal ganglia-thalamocortical circuits
Skeletomotor, oculomotor, prefrontal, limbic circuit
57
What is the cortico-basal-thalamocortical motor circuit
Sensorimotor cortical fields -> putamen -> motor portions of GPi and SNr -> VLo/VA in thalamus -> M1/SMA/PM
58
What subcortical feedback loop is involved in the cortico-basal thalamocortical motor circuit
The GPi and SNr also project to the centromedian nucleus of the thalamus -> putamen
59
How does the basal ganglia output map onto M1/SMA/PM
Separate populations of neurons in specific areas of the basal ganglia structures (and thalamus) project to the M1, SMA and PM- the cortical subcircuits remain segregated
60
What motor roles has the motor circuit of the basal ganlglia been implicated in
Action/goal selection, preparation for movement, initiation desired movement, inhibiting unwanted movements, sequencing of movement
61
How may the basal ganglia act as a focusing model?
Simultaneous activation of the direct pathway and indirect pathway facilitates intended movements and suppresses competing ones
62
Issues with the basal ganglia focusing model- not anatomically supported
Requires indirect pathway to target large areas of the pallidum to prevent unwanted movements while the direct pathway acts on small areas of the GPi to selectively facilitate selected ovement- not supported by anatomical evidence
63
Neural activity of basal ganglia- movement preparation
Monkey basal ganglia motor areas in delayed-response tasks shows changes in firing frequency when desired movement direction is cued
64
Neural activity of basal ganglia- movement execution
Some basal ganglia neurons change their firing rate in relation to the onset of movement, suggesting they are concerned with movement execution
65
Neural activity of basal ganglia- scaling movement
Activity changes in GPi correlate with amplitude and velocity of movement, while some correlate with overall direction of movement, suggesting role in higher-aspects of movement
66
What neurons in the basal ganglia are associated with reinforcement motor learning
Many DA neurons in SNc that project to the striatum are correlated with behaviour reinforcement cues Cholinergic interneurons in the striatum have their tonic activity reduced by rewards/noxious stimuli
67
What are the respective roles of dopaminergic input and cholinergic intereurons in the striatum in motor learning
Cholinergic interneurons signal MSNs about the OCCURANCE of salient stimuli, while dopaminergic inputs signal the behavioural VALUE of stimuli
68
What is the reward prediction error
A discrepancy between the expectation of a reward and its delivery
69
What signals the reward prediction error
Changes in the activity of DA cells- DA release strengthens synapses involved in generating the rewarded behaviour, reinforcing that behaviour
70
How can DA and ACh affect the strength of synapses in the basal ganglia
LTP, LTD, or spike-time dependent modulation
71
What abnormality of neuronal activity may underlie Parkinsons
Abnormal burst discharges and firing patterns, unusual oscillatory neuronal activity
72
What frequency oscillation is associated with Parkinsons
High amplitude alpha/beta frequency oscillation in the STN and GPi- may prevent oscillations at higher gamma band frequencies, needed for normal movement
73
How may DBS work by providing high-frequency stimuliation
Replaces the irregular abnormal basal ganglia output with a more regular tolerable pattern, or disrupts abnormal beta frequency oscillations

Neurophysiology (23 decks)

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