Basal Ganglia Flashcards
Where is the basal ganglia located?
lie deep within the cerebral hemispheres and in the anterior part of the midbrain (substantia nigra)
lateral to the thalamus
What are the four functions of the basal ganglia?
- regulating involuntary movement
- tuning voluntary movement
- maintaining posture
- involving in non-motor brain function
How does the basal ganglia affect movement?
does not intitate movement directly but instead modulates movement by influencing motor circuits in the brain
What are the 3 components of the basal ganglia?
- striatum
- pallidum
- subthalamic nuclei
What are the 2 components of the striatum (BG)?
- caudate
- putamen
What are the 2 components of the pallidum (BG)?
- global pallidus (internal and external)
- substantia nigra pars reticulata
Where is the location of the striatum (BG)?
input zone
Where is the location of the pallidum (BG)?
output zone
What is the main neuronal type of the striatum (BG)?
medium spiny neurons (MSN)
D1 and D2 MSNs
What is the main neuronal type of the pallidum (BG)?
globulus pallidus - large inhibitory GABAergic projection neurons
substantia nigra - dopaminergic neurons
What are the physiological properties of the striatum (BG)?
low spontaneous activity
requires strong excitation
What are the physiological properties of the pallidum (BG)?
high spontaneous activity
continuously inhibits targets
What is the function of the striatum (BG)?
process motor and cognitive inputs
What is the function of the pallidum (BG)?
regulates movement via inhibitory outputs -> creates of smooth muscle and precise motor actions
Where does the striatum receive inputs from?
the cortex
thalamus
substantia nigra pars compasta
Where does the striatum send outputs to?
internal part of globus pallidus - direct pathway
external part of globus pallidus - indirect pathway
Where does the pallidum send outputs to?
thalamus
substantia nigra pars compasta to the striatum
substantia nigra pars reticulate to the brainstem
Where doe MSN receive inputs from?
the cerebral cortex
local circuit interneurons of the striatum
neurons in the midline and intralaminar nuclei of the thalamus
neurons in several nuclei of the brainstem
How many neurons doesnthe striatum contain?
about 100 million
about 75% MSN
What is the function of MSN?
have large dendritic trees which allow then to collect and integrate input from a variety of cortical, thalamic, and brainstem structures
Where do axons arising from MSN converge?
in the pallidum
What are the 2 key features of MSN?
- they are GABAergic output neurons that recive dopaminergic input
- they have unique biophysical properties due to the expression of a specific type of potassium channels
Where are dopaminergic synapses located?
originates in the substantia nigra pars compacta
on the base of the spine in close proximity to the cortical synapse where they selectively modulate cortical imput
What is the action of D1R receptors on MSN and dopamine?
excitatory inputs to the MSN that project to the internal globus pallidus (direct pathway)
What is the action of D2R receptors on MSN and dopamine?
inhibitory inputs to the MSN that projecr to the external globus pallidus (indirect pathway)
What is the major functional difference between D1R and D2R receptors?
D1Rs mediate the activation of G proteins that increase cAMP
D2Rs act through different G proteins that decrease cAMP
-> D1Rs enhance the excitatory input from cortex and D2Rs supress this excitation
What is the action of inward-rectifier K+ channels?
in MSN remain open at resting potential ->
stabilizing the membrane and making spontaneous diring unlikely ->
MSN require strong excitatory input from multiple sources to overcome potassium conductance and fire an AP ->
when the neuron depolarizes these channels close making the neurons more excitable
When do MSNs typically increase their rate of discharge?
before an impeding movement
When do MSNs typically start firing?
associated with the occurance of a movement
Explain the premovement neuronal activity of MSNs may encode?
the activity of these cells may encode the decision to move toward a goal rather than the direction and amplitude of the actual movement necessary to reach the goal
What type of neurons are in the pallidum?
efferent cells of both the globus pallidus and substantia nigra pars reticulata are GABAergic -> the main output of the BG is inhibitory
How many neurons is the globus pallidus comprised of?
about 700 000 cells
on average more than 100 MSNs innervate each cell
What is the output activity of neurons in the pallidum and what does it prevent?
high levels of spontaneous activity
prevent unwanted movement by tonically inhibiting cells in the thalamus and superior colliculus
What are the 3 main projection to the BG?
- the corticostriatal pathway
- the thalamostriatal pathway
- pathway from substantia nigra pars compasta
What are the 3 main projection from the BG?
- from the striatum
- from the globus pallidus
- from teh substantia nigra pars reticulata
Where does the caudate recieve projection from in the corticostriatal pathway?
multimodel association cortices
motor areas in the frontal lobe that control eye movement
Where does the putamen recieve projection from in the corticostriatal pathway?
the primary and secondary somatosensory cortices in the parietal lobe
the higher order visual cortices in the occipital and temporal lobe
the premotor and primary motor cortices in the frontal lobe
the auditory association areas in the temporal lobe
What are the direct and indirect pathways from the striatum?
direct - to internal part of the globus pallidus
indirect - to external part of the globus pallidus and the substantia nigra pars reticulata
What is the pathway from the globus pallidius?
to the ventral anterior and ventral lateral nuclei of the dorsal thalamus -> motor areas of the cerebral cortex
What is the pathway from the substantia nigra pars reticulata?
to the superior colliculus that command head and eye movements, without an intervening relay in the thalamus
What activates the direct and indirect pathways withing the BG?
integration of cortical inputs by the striatum
What is the the balance of the activity mediated by the direct and indirect pathways the principal determinant of?
whether the output from the pallidum to to the thalamus or superior colliculus
How are the direct and indirect pathways functionally organized?
in a centre-surround fashion withing the output nuclei of the basal ganglia
What does co activation fo both sets of striatal neurons imporant for?
the smooth initiation and execution of new motor activites
Explain the direct pathway (BG)
activation leads to the focal inhibition of a more restricted “center” cluster of neurons in the internal segment ->
the disinhibition of the VA/VL thalamic complex and the expression of the intended motor program
cortex -> striatum (-) -> IGP (-) -> thalamus
EXCITATORY
Explain the disinhibition circuit of the direct pathway
the pallidal cells are inhibited by activation of the MSNs ->
the globus pallidus neurons provide tonic inhibition to the relay cells in the VL/VA nuclei of the thalamus ->
the thalamus neurons are disinhibited and can trigger the activation of upper motor neurons in the cortex ->
allows the upper motor neurons to send commands to local circuit neurons and lower motor neurons that, in turn, initiate movement
Explain the indirect pathways (BG)
the external segment of the globus pallidus sends projections to both the adjacent internal segment and the subthalamic nucleus of the ventral thalamus
with activation of the indirect pathways, the MSNs discharge and inhibit the tonically active GABAergic neurons of the external globus pallidus ->
the subthalamic cells become more active and due to their excitatory connections with the GABAergic cells in the internal segment of the globus pallidus and substantia nigra pars reticulata they increase the inhibitory output of the basal ganglia
also the subthalamic nucleus recives excitatory projections from the cerebral cortex
cortex ->striatum (-) -> EGP (-) -> subthalamic nucleus (+) -> IGP (-) -> thalamus
INHIBITORY
How does teh BG contribute to saccadic eye movements?
shortly before the onset of a saccade the tonic discharge rate of the reticulata neurons is sharply reduced by input from GABAergic MSNs of the caudate which have been activated by signals from the cortex ->
this disinhibits the upper motor neurons of the superior colliculus allowing them to generate the bursts of APs that command saccades ->
the projections from the substantia nigra pars reticulata to the upper motor neurons act as a physiological “gate” that must be “opened” to allow either sensory or other higher order signals from cognitive centers to activate the upper motor neurons and initiate a saccade
What are the two classes of disorders associated with the BG?
hypokinetic movement disorders - parkinsons
hyperkinestic movement disorders - huntingtons
What is the cause of Parkinsons?
loss of dopaminergic neurons in the substantia nigra pars compacta
What is parkinsons effects on pathways?
less dopamine ->
overactive indirect pathway ->
excess inhibiton of the thalamus -> less movement
What are the symptoms of parkinsons?
bradykinesia (slow movement)
resting temor
rigidity
postural instability
What is the treatment for Parkinson’s?
L-DOPA therapy (resotre dopamine levels)
deep brain stimulation (targets STN or GPi)
What is the cause of huntingtons disease?
degeneration fo the MNs in the indirect pathway
What is huntingtons effects on pathways?
loss of indirect pathway inhibition -> excess activation of the thalamus -> uncontrolled movement
What are symptoms of Huntingtons?
chorea (involuntary jerky movements)
cognitive decline
emotional distrubances
What is the treatment for huntingtons?
symptomatic management with dopamine antagonsits
Explain how hyperkinesia is modelled in animals?
a GABA antagonist is injected into the SNr reducing tonic activity ->
removes the inhibitory control over the SC leading to disinhibiton of the SCs upper motor neurons ->
generates involuntary saccadic eye movements (spontaneous and irrepressible) ->
direction of saccades depend on the injection site within the SNr (spatially organized with motor maps corresponding to saccade vectors in the visual field)
What is deep brain stimulation?
the implantaion of battery powered generator untis usually near the clavicles
produce electrical discharges that are passed through subcutaneous wires to electrodes implanted bilaterally into the brain
What are the two most common sites for DBS in individuals with movement disorders?
the internal segment of the globus pallidus
the subthalamic nucleus
What can the exogenous induction fo electrical currents in DBS lead to?
complex patterns of activity and inactivity in the affected neural elements as well as effects on non neural elents
different intensities may lead to the local release of neurotransmitters and neuromodulators
