TASK 2 - BASAL GANGLIA Flashcards Preview

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Flashcards in TASK 2 - BASAL GANGLIA Deck (27)
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1
Q

basal ganglia

A

= large set of nuclei

  • caudate, putamen, globus pallidus: motor components
  • telencephalon, diencephalon (sub thalamic nuclei), mesencephalon (substantiva nigra)
  • links most of the cerebral cortex with upper motor neurones in M1, premotor cortex and in the brainstem
2
Q

role of basal ganglia in movement

A
  • (+ cerebellum) influence movement by regulating activity of upper motor neurons –> no direct projection to local circuit or lower motor neurones
  • facilitate movement initiation
  • facilitate suppression of competing motor programs that would otherwise interfere with expression of goal-directed behaviour
  • modulation of activity in anticipation of and during movements (smooth movements)
3
Q

input nuclei

A
  • cortex = largest input to basal ganglia; only primary visual + auditory cortex have no projections to the striatum
    1. striatum: almost all input; from much of cerebral cortex (mostly from frontal and parietal lobes, followed by temporal, insular and cingulate cortices)
  • -> corticospinal pathway = multiple pathways serving different functions
    a. caudate
    b. putamen
    2. substantia nigra pars compacta
4
Q

input nuclei

1. striatum

A
  • input zone, destinations of most pathways + incoming axons from the cerebral cortex and other parts of the brain
  • medium spinal neurones = large dendritic trees that can integrate various inputs
  • GABAergic neurones
  • functionally subdivided to its inputs –> reflects specialisation of cortical areas that provide input
5
Q

striatum

1a. caudate

A
  • input from association cortices + motor areas in frontal lobe that control eye movements (FEF)
  • occumolotor loop
  • anticipatory discharge of eye movements
6
Q

striatum

1b. putamen

A
  • input from primary, secondary somatic sensory cortices in parietal lobe + secondary (extrastriate) visual cortices in occipital and temporal lobes + premotor and motor cortices in frontal lobe + auditory association areas in the temporal lobe
  • motor loop
  • anticipatory discharge of limb and trunk movements
  • activity in these cells encode decision to move toward a goal
7
Q

input nuclei

2a. substantia nigra pars compacta

A
  • input: main dopaminergic aminergic inputs originate
  • inputs relatively far from the initial segment of the medium spiny neurone axon
  • neurones exhibit very little spontaneous activity and must simultaneously receive many excitatory inputs from cortical and nigral neurones to overcome stabilising influence of this potassium conductance (which remains a stable resting membrane potential, close to depolarisation)
8
Q

output nuclei

A
  • major pathways that allow basal ganglia to influence activity of upper motor neurones located in motor cortex and brainstem; 2 pathways
  • GABAergic neurones/output = high levels
  • activity prevents unwanted movements by tonically inhibiting cells in thalamus and superior colliculus
    1. pallidum: main sources of output
    a. globus pallidus: large number of myelinated axons (pale)
    b. substantia nigra pars reticular: reticular/netlike form
9
Q

pallidum

3. globus pallidus

A
  • pathway to cortex
    1. globus pallidus internal (GPi)
    2. relays in ventral anterior + ventral lateral nuclei of dorsal thalamus
    3. project directly to motor areas (M1, SMA, PFC)
  • motor loop: multiple areas of cortex –> processing in basal ganglia and thalamus –> terminating in motor areas
10
Q

pallidum

2b. substantia nigra pars reticulata

A
  • control head and eye movements
    1. substantia nigra pars reticulata (SNr)
    2. project to + terminate in superior colliculus (initiation of eye movement)
  • more direct: without intervening relay in thalamus
  • many also project to thalamus to relay info to frontal eye fields and premotor cortex
11
Q
  1. subthalamic nuclei
A
  • ventral thalamus

- diencephalon

12
Q

direct pathway

A
  1. activation of medium spiny neurones in input nuclei (= striatum)
  2. inhibition of GPi
  3. disinhibition of ventral thalamus
  4. activation of frontal cortex
13
Q

direct pathway

- dopamine pathway

A
  • substantia nigra (SNc) excites direct pathway via acting on D1 receptor –> striatum excited = inhibits GBi MORE
  • ENHANCES EFFECT = more wanted movement (centre action is strongly supported)
14
Q

indirect pathway

A
  1. activation of striatum
  2. inhibition of GPe
  3. disinhibition of STN
  4. MORE activation of GPi
  5. MORE inhibition of thalamus
  6. NO activation of frontal cortex
15
Q

indirect pathway

- dopamine pathway

A
  • substantia nigra (SNc) inhibits indirect pathway via acting on different type of D2 receptor (D2) –> striatum inhibited = inhibits GPe LESS
  • REDUCES EFFECT = more unwanted movement (surrounding actions more uncontrolled)
16
Q

centre-surround functional organisation

A
  • direct pathway = centre = activation of intended motor programs
  • -> facilitation of voluntary movements
  • indirect pathway = surround = suppression of competing motor programs
  • -> suppression of inappropriate movements
17
Q

dopamine pathway

A
  • internal pathway
  • role: contribute to reward-related modulation of behaviour
  • EXCITES direct pathway
  • INHIBITS indirect pathway
18
Q

basal ganglia disorders

- Parkinson’s disease

A

= hypokinetic movement disorder
= failure of disinhibition
- causes: loss of nigrostriatal dopaminergic neurones
- results in abnormally high inhibitory output of the basal ganglia –> lesser thalamic activation of upper motor neurones
- motor symptoms: resting tremor, slowness of movement (= bradykinesia); diminished facial expressions, lack associated movements (= akinesia) –> failure of normal disinhibition
- cognitive symptoms: lack of cognitive drive/motivation, decision making deficits; sometimes associated with dementia
- any movement is difficult to initiate + once initiated often difficult to terminate
- not able to act on internal cues BUT on external cues

19
Q

Parkinson’s disease

- pathways

A

dopamine pathways degenerated:

  1. less facilitation of direct pathway = less activation of voluntary movements
    - increases responsiveness of direct pathway to corticospinal input
    - more inhibition of thalamus
  2. less reduction = suppression of inappropriate movements
    - decreases responsiveness of indirect pathway to input
    - more inhibition of thalamus
    - -> MORE INHIBITION = less movement initiation; cortex almost impossible to activate
20
Q

Parkinson’s disease

- treatment

A
  • l-DOPA
  • stem cells, gene therapy
  • deep brain stimulation: GPe, STN, GPi
21
Q

basal ganglia diseases

- Huntington’s disease

A

= hyperkinetic movement disorder
= failure of Inhibition
- causes: degeneration of medium spiny neurons (striatum) that project to the globus pallidus (GBe) –> atrophy of caudate and putamen (striatum)
- results in abnormal activation of GPe –> reduces excitatory output of STN to GPi + inhibitory outflow of basal ganglia –> without restraining influence upper motor neurones can be activated by inappropriate signals
- symptoms: involuntary movements; alteration in mood/change in personality (increased irritability…); defects of memory and attention; rapid, jerky motions with no clear purpose (= choreiform movements)

22
Q

Huntington’s disease

- pathways

A

medium spiny neurones degenerated = GBe degenerated:

  1. more inhibition of direct pathway on GPe = more activation of voluntary movements
    - more activation of thalamus
  2. less activation of indirect pathway on GPe = less suppression of involuntary movements
    - more activation of thalamus
    - -> MORE ACTIVATION = less control of movements; cortex easily activated
23
Q

Huntington’s disease

- treatment

A
  • deep brain stimulation

- gene therapy: antisense treatment

24
Q

cortico-striatal-thalamic loops

1. motor loop

A

= action, movement

  1. motor areas (SMA)
  2. putamen
  3. lateral GPi
  4. ventral lateral + ventral anterior thalamic nuclei
25
Q

cortico-striatal-thalamic loops

2. occumolotor loop

A
  • eyes
    1. frontal eye field (FEF), PPC, PFC
    2. caudate
    3. GPi, SNr
    4. mediodorsal + ventral anterior thalamic nuclei
26
Q

cortico-striatal-thalamic loops

3. cognitive loop

A
  • cognition
    1. DLPFC
    2. anterior/dorsolateral caudate (literature vs. lecture BUT caudate)
    3. GPi, SNr
    4. mediodorsal + ventral anterior thalamic nuclei
27
Q

cortico-striatal-thalamic loops

4. limbic loop

A
  • motivation/emotion
    1. limbic system (anterior cingulate: emotion; orbitofrontal cortex: motivation)
    2. ventral striatum: emotion (ventromedial caudate: motivation)
    3. ventral pallidum
    4. mediodorsal thalamic nuclei