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Neurophysiology > Basal ganglia > Flashcards

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
Q

What output does the substantia nigra pars compacta (SNc) do

A

Ascending dopamine input to the striatum

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26
Q

What is the result of striatal excitation in the DIRECT PATHWAY

A

Striatum inhibits SNr/GPi, reduced GPi inhibition of thalamus
Facilitates movement

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27
Q

What is the result of striatal excitation in the INDIRECT PATHWAY

A

Striatum inhibits GPe, reduced GPe inhibition of STN
Excitation in STN excites the GPi, increasing its inhibition of the thalamus
Inhibits movement

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28
Q

Which of the direct vs indirect pathways facilitates vs inhibits movement

A

DIRECT PATHWAY- faciliates movement

INDIRECT PATHWAY- inhibits movement

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29
Q

How do D1 and D2 receptors segregate in the direct vs indirect pathway

A

Direct pathway- D1 receptors

Indirect pathway- D2 receptors

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30
Q

What is the effect of dopamine on the direct pathway

A

D1 DA receptors on direct striatal projections FACILITATE the pathway, facilitating movement

31
Q

What is the effect of dopamine on the indirect pathway

A

D2 DA indirect striatal projections INHIBIT the pathway, facilitating movement

32
Q

What effect does dopamine from SNc have on the direct and indirect pathway

A

FACILITATES MOVEMENT IN BOTH PATHWAYS

Facilitates the direct pathway, inhibits the indirect pathway

33
Q

List some examples of basal ganglia diseases

A

Parkinsons’, drug-induced Parkinsons, Huntingsons, Tourettes

34
Q

OVERALL symptoms of basal ganglia diseas

A

Deficiency of movement, involuntary movements

35
Q

Symptoms of basal ganglia disease- deficiency of movement examples

A

Akinesia, bradykinesia

36
Q

Symptoms of basal ganglia disease- involuntary movements examples

A

Tremor at rest, dystonias, chorea, tics, dyskinesias

37
Q

Primary motor symptoms of Parkinsons

A

Akinesia, tremor at rest, rigidity, postural instability (TRAP)

38
Q

Non-motor dysfunction in Parkinsons

A

Problems with sleep behaviour, depression, cognition, pain, dementia, bowels

39
Q

What neuronal changes underlie Parkinsons

A

Progressive loss of SNc DA neurons (DA facilitates movement)

Proteinaceous aggregations

40
Q

What are proteinaceous aggregations in Parkinsons

A

Lewy bodies- intraneuronal cytoplasmic inclusions

Major components are a-synuclein and ubiquitin

41
Q

How does the intrinsic physiology of SNc neurons promote their vulnerability to Parkinsons

A

Very highly arborised means high metabolic demand

Oxidative stress, neuroinflammation, protein misfolding and accumulation

42
Q

Environment contributions to Parkinsons

A

Neuroinflammation, pesticides + genetics, toxin exposure (MPTP toxicity)

43
Q

What causes MPTP toxicity

A

Selective entry of MPP+ into DA neurons leads to downstream increase of ROS (reactive oxygen species) via DA dumping, causing selective death

44
Q

What key drug treatment is used for Parkinsons

A

L-DOPA (precursor of dopamine) PLUS an inhibitor of peripheral decarboxylase
Increased dopamine production

45
Q

How is L-DOPA problem as a treatment for Parkinsons

A

On/off effects, gait freezing, LDOPA induced dyskinesia typically occur within 5-10 years of LDOPA therapy

46
Q

Alternative Parkinsons therapy options to LDOPA

A

DA agonists, gene therapy, transplans, DBS

47
Q

How does deep brain stimulation work

A

Stimulating electrode implanted during surgery into basal ganglia nuclei eg STN, GP
High frequency stimulation

48
Q

Symptoms of Huntington’s chorea

A

Usually hyperkinetic

Chorea, dystonia, rigidity and cognitive decline

49
Q

What changes occur to brain structure in Huntington’s chorea

A

Striatal atrophy-loss of caudate nucleus GABAergic medium spiny neurons (particularly D2)
Cortical atrophy

50
Q

Underlying causes of Huntington’s disease

A

Genetics, ‘codon-repeat disease’ that encodes consecutive polyglutamines from huntingtin gene (HTT), HTT protein aggregates

51
Q

How do brain structure changes in Huntington’s cause its hyperkinetic phenotype

A

D2 neurons especially affected, meaning the direct pathway dominates the indirect pathway, causing decreased inhibition of the thalamus

52
Q

Treatments for Huntingtons

A

Antidopaminergics, tetrabenazine, neuroleptics, benzodiazepines

53
Q

Where does the thalamus project to

A

The frontal lobe, the same areas that provided the basal ganglia with input

54
Q

What is the neurotransmitter identity of STN output

A

Glutamatergic

55
Q

What are the maps in the basal ganglia like

A

Topographical maps of the area of cerebral cortex they receive input from
Some of these cortex areas receive input from the other lobes

56
Q

Examples of basal ganglia-thalamocortical circuits

A

Skeletomotor, oculomotor, prefrontal, limbic circuit

57
Q

What is the cortico-basal-thalamocortical motor circuit

A

Sensorimotor cortical fields -> putamen -> motor portions of GPi and SNr -> VLo/VA in thalamus -> M1/SMA/PM

58
Q

What subcortical feedback loop is involved in the cortico-basal thalamocortical motor circuit

A

The GPi and SNr also project to the centromedian nucleus of the thalamus -> putamen

59
Q

How does the basal ganglia output map onto M1/SMA/PM

A

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
Q

What motor roles has the motor circuit of the basal ganlglia been implicated in

A

Action/goal selection, preparation for movement, initiation desired movement, inhibiting unwanted movements, sequencing of movement

61
Q

How may the basal ganglia act as a focusing model?

A

Simultaneous activation of the direct pathway and indirect pathway facilitates intended movements and suppresses competing ones

62
Q

Issues with the basal ganglia focusing model- not anatomically supported

A

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
Q

Neural activity of basal ganglia- movement preparation

A

Monkey basal ganglia motor areas in delayed-response tasks shows changes in firing frequency when desired movement direction is cued

64
Q

Neural activity of basal ganglia- movement execution

A

Some basal ganglia neurons change their firing rate in relation to the onset of movement, suggesting they are concerned with movement execution

65
Q

Neural activity of basal ganglia- scaling movement

A

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
Q

What neurons in the basal ganglia are associated with reinforcement motor learning

A

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
Q

What are the respective roles of dopaminergic input and cholinergic intereurons in the striatum in motor learning

A

Cholinergic interneurons signal MSNs about the OCCURANCE of salient stimuli, while dopaminergic inputs signal the behavioural VALUE of stimuli

68
Q

What is the reward prediction error

A

A discrepancy between the expectation of a reward and its delivery

69
Q

What signals the reward prediction error

A

Changes in the activity of DA cells- DA release strengthens synapses involved in generating the rewarded behaviour, reinforcing that behaviour

70
Q

How can DA and ACh affect the strength of synapses in the basal ganglia

A

LTP, LTD, or spike-time dependent modulation

71
Q

What abnormality of neuronal activity may underlie Parkinsons

A

Abnormal burst discharges and firing patterns, unusual oscillatory neuronal activity

72
Q

What frequency oscillation is associated with Parkinsons

A

High amplitude alpha/beta frequency oscillation in the STN and GPi- may prevent oscillations at higher gamma band frequencies, needed for normal movement

73
Q

How may DBS work by providing high-frequency stimuliation

A

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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