Basal Ganglia Flashcards
Basal Ganglia
Overview
Motor control center for regulation of movement.
Does not generate motor commands.
Provides gain control by ∆ combinations, directions, and sequences of movements via indirect connections:
BG → thalamus → cortex → spinal cord
BG → reticular formation → PRST & MRST
Basal Ganglia
Functions
- initiation and termination of movement
- context switching between patterns of movement
- sequence learning
- reinforcement learning
- combining limbic drive with motor action
Also involved in cognitive functions.
Basal Ganglia
Dysfunction
Results in progressive motor symptoms of excessive or deficient movement, or both.
Includes:
- rigidity involving active contractions
- slowed or absent ability to initiate movements
- loss of postural reflexes
- involuntary and inappropriate movements
Basal Ganglia
Structures
Group of 5 main forebrain structures:
- Caudate nucleus
- Putamen
-
Globus pallidus
- internal segment (GPi)
- external segment (GPe)
- Subthalamic nucleus (STN)
-
Substantia nigra (SN)
- pars compacta (pC or SNc)
- pars reticulata (pR or SNr)
Caudate + putamen = striatum (STR)
Putamen + globus pallidus = lenticular nucleus
Nucleus accumbens and ventral pallidum sometimes considered part of the basal ganglia.
Blood Supply
Supplied mainly by perforating branches of 3 arteries:
Caudate nucleus:
ACA, MCA, and anterior choroidal artery (AChA)
Putamen:
ACA and MCA
Globus pallidus:
anterior choroidal and MCA
Striatum
Characteristics
Caudate + Putamen
- Similar cell types, afferents, and efferents
- Extent and pattern of cortical projections produces functional differences
- Afferents from 3 major inputs converge onto the same striatal cells.
- Cortical and thalamic inputs ⟾ distally on dendrites of striatal spiny neurons
-
SNc DA inputs ⟾ proximally
- able to modulate effects of other inputs
Striatum
Inputs
-
Cortical input:
- Glutamatergic → ⊕ distal spiny neurons
- Significant input from all cortical areas
- Cognitive and affective areas → caudate n.
- Primary motor and sensory areas → putamen
- Primarily ipsilateral
- Topographically organized
- maintained throughout BG
-
Thalamic input:
- Mainly from intralaminar nuclei
- CM thalamus → caudate n.
- Parafascicular n. → putamen
- Thalamic n. receive convergent input from many sources and sensory modalities
- Mainly from intralaminar nuclei
-
SNc input:
- Sign. input from dopaminergic neurons
- Modulates effects of other inputs
- Destroyed in Parkinson’s disease and by MPTP neurotoxin
Striatum
Outputs
- Projects to globus pallidus and substantia nigra
- Mainly GABAergic → inhibitory
- Also uses enkephalin, dynorphin, and substance P
- Topographic organization received from cortex perserved in projections
Globus Pallidus
Globus pallidus externa (GPe)
- GABA/enkepalin striatal input
- Projects mainly to STN
- GABAergic → inhibitory
Globus pallidus interna (GPi)
- GABA/Substance P striatal input
- One of two major BG output pathways
- GABAergic → inhibitory
-
Thalamic projection (VA >>> VL and CM)
-
Pallidothalamic projections forms 2 fiber bundles
-
Ansa lenticularis
- originates from GPi areas receiving caudate n. input
- projects to VA thalamus
-
Lenticular fasciculus
- originates from GPi areas receiving putamen input
- projects to VL and CM
-
Ansa lenticularis
-
Pallidothalamic projections forms 2 fiber bundles
- Mesencephalic reticular formation
- Pedunculopontine nucleus
Subthalamic Nucleus
(STN)
Contains glutamatergic neurons.
Only basal ganglia n. with pure excitatory function.
GPe → STN → GPi
Cortex & SNc → STN → SNr
Unilateral STN lesion ⟾ contralateral hemiballism.
Substantia Nigra
Pars compacta (SNc)
- pigmented cells contain melanin
- dendrites extend into SNr
- affected by SNr inputs
- Dopaminergic neurons project mainly to striatum ⟾ nigrostriatal pathway
- Lost in Parkinson’s disease
Pars reticulata (SNr)
-
Inputs:
- striatal neurons ⟾ GABA
- subthalamic neurons ⟾ Glu
-
Major output n. of basal ganglia (GABAergic)
- Nigro-thalamic → VA
-
Nigro-tectal → superior colliculus
- control of eye movements
- Mesencephalic reticular formation
Basal Ganglia
Circuits Overview
Basal ganglia inputs and outputs organized into two circuits ⟾ direct and indirect.
- Both activated by excitatory inputs from cortex.
- Functions to disinhibit thalamic/RF targets of BG
- Both with inhibitory output mainly to:
-
VA thalamus
- ⊕ ⟾ premotor & supplementary motor
- involved in generation of movements
-
Pediculopontine nucleus (PPN) of RF
- ⊖ ⟾ spinal cord circuits
- involved in postural control
-
VA thalamus
-
Direct path:
- disinhibition of VA and PPN
- faciliates motor synergies
- suppresion of postural control
-
Indirect path
- increased inhibition of VA and PPN
- promotes inhibition of motor synergies
- faciliates postural control
Modular Loops
Circuits show tight somatotopic organization within striatum, globus pallidum, STN, and corticothalamic loops.
Specific areas of each component projects to a specific area of the next.
Eventually projects back to original cortex area.
Establishes a modular organization within corticothalamic and basal ganglia loops.
Direct Pathway
Cortical activation of direct path inhibits spontaneous activity of Gpi/SNr cells
⟾ disinhibition of VA and PPN
⟾ increases activation of motor cortices
⟾ promotes initiation and facilitation of movements (VA)
⟾ suppresses postural control (PPN)
Mechanism
- Motor plan from cortex to striatum.
- Glu → ⊕ GABA/substance P neurons of direct path.
- ↑ GABA/substance P → ⊖ GPi/Snr
- ↓ GPi/Snr inhibits less VA thalamus
- Disinhibited VA → ⊕ Glu → activates more the premotor and supplementary motor cortices
Indirect Pathway
Cortical activation of indirect path inhibits GPe neurons.
⟾ disinhibition of STN
⟾ ↑ STN activation of GPi/SNr
⟾ ↑ inhibition of VA/PPN
⟾ promotes inhibition of movement (VA)
⟾ facilitation of postural control (PPN)
Mechanism
- Motor plan from cortex → striatum (indirect path)
- Glu → ⊕ GABA/enkephalin neurons
- ↑ [GABA/enkephalin] → ⊖ GPe
- Inhibited GPe inhibites less STN
- Disinhibited STN via Glu activates more GPi/SNr
- Activated GPi/SNr via GABA inhibites more VA/PPN
- Inhibited VA activates less motor cortices.
- Inhibited PPN inhibites less spinal cord pathways.
Effects of Dopamine
Dopamine released by SNc acts on STR and STN.
⊕ direct path via D1 receptors
⊖ indirect path via D2 receptors
Net effect of DA to facilitate movement.
Modulates how systems process information.
Affects how quickly they switch on and off movement.
Loss of modulation causes direct and indirect circuits to ‘jam’.
Direct Path
Altered Activity
-
Overactivity
- ↓ GPi/SNr
- ↑ VA/PPN
- Excessive movement
- Decreased postural control
-
Underactivity
- ↑ GPi/SNr
- ↓ VA/PPN
- Voluntary movement difficult and slow
- Increased postural control = rigidity
Indirect Path
Altered Activity
-
Overactivity
- ↑ GPi/SNr
- ↓ VA/PPN
- Voluntary movement difficult and slow
- Increased postural control = rigidity
-
Underactivity
- ↓ GPi/SNr
- ↑ VA/PPN
- Involuntary movement
- Decreased postural control
Parkinson’s Disease
Mechanism
Caused by loss of dopaminergic neurons within SNc.
-
Direct pathway becomes underactive (D1)
- generation of movement difficult and slow
- postural control increased
-
Indirect path becomes overactive (D2)
- difficult to initiate movement
- rigidity
Parkinson’s
Symptoms & Treatment
-
Positive motor symptoms
-
Tremor at rest
- “pill-rolling”
- postural tremor
- Cogwheel or lead pipe rigidity
- Involuntary movements (akathesia)
-
Tremor at rest
-
Negative motor symptoms:
-
Bradykinesia
- shuffling gait (marcher a petit pas)
- expressionless face (masked facies)
- povery of blinking
- lack of spontaneous speech
-
Postural disturbances
- head droop
- stooped posture
- impaired righting
-
Bradykinesia
-
Treatments:
- L-Dopa
- Grafting of DA containing cells (fetal mesencephalon)
- Lesion in/around VA/VL nucleus, pallidum, or STN.
-
Deep brain stimulation (DBS)
- likely functions by unjamming or functional lesion of STN action on movement
Huntington’s Corea
Mechanism
Efferent neurons of striatum progressively destroyed.
Starts in caudate n. and progresses to putamen.
Early Phase
GABAergic/Enkephalin & cholinergic cell degeneration.
-
Indirect path becomes underactive
- ↑ GPe → ↓ STN → ↓ GPi/SNr → ↑ VA/PPN
- Excessive and involuntary movements
- Decreased postural control
Late Phase
GABA/substance P cells also degenerate.
-
Direct path becomes underactive
- failure to initiate normal movements
- akinesia
- rigidity
Huntington Chorea
Symptoms and Treatment
- Symptoms
- chorea
- cognitive impairment (dementia)
- psychiatric disturbances
- death 15-20 years after onset
- Treatment
- Palliation of motor and affective sx
Hemiballismus
Due to lesion in STN.
-
↓ GPi/SNr → ↑ VA/PPN
- Reduced input from GPi allows thalamocortical neurons to respond in exagerated manner
- inc. tendency to discharge spontaneously
- Results in involuntary violent movements of contralateral limbs
Tardive Dyskinesias
- Caused by certain medications including neuroleptics and anti-psychotics.
- Temporarily alters or permanently damages basal ganglia function.
- May be caused by denervation hypersensitivity of dopamine receptors.
- Sx. include involuntary tongue protrusion and grimacing.
