Basal Ganglia Flashcards
What are the components of the basal ganglia?
Subcortical region (nuclei within the brain)
- caudate and putamen make up the **striatum **
- globus pallidus (internal and external)
- subthalamis nuclei
**Brainstem **
- Substantia nigra pars compacta
- Substantia nigra pars reticulata
The caudate and putamen (striatum) receive input from multiple cortical, thalamic, and brainstem regions. Name them
Brainstem inputs
- dopaminergic axons from the substantia nigra pars compacta (Sn-C)
Cortical Inputs (= corticostriatal pathway)
- Greatest number of inputs is from frontal and parietal lobe association cortices
- Caudate inputs are primarily from 1) frontal lobe areas that control eye movements and 2) association cortices.
- Putamen receives input from 1ª and 2ª visual cortex, motor and premotor cortex and auditory association cortex
Logical organization of inputs to the caudate/putamen. That is related regions of the cortex will have their inputs to the caudate/putamen in close proximity to one another.
association cortex
a cortical region that receives and integrates input from multiple sensory modalities
medium spiny neurons projections (edit maybe)
Project out of striatum and to their targets at either GPi or GPe.
Axons that form the corticospinal path are actual collaterals from other cortical pathways (e.g. corticocortical, corticospinal).
Number of glutamatergic synpatic contacts between a single cortical axon and medium spiny neuron is small, but a medium spiny neurons each receive input from 1000s of different cells
therefore, the striatal medium spiny cells are integrating inputs from a large number of sources
MSNs receive input from..
Cortical input
local interneurons (onto soma)
DA neurons from Substantia Nigra pars compacta
Other striatal medium spiny neurons (not shown in lecture figure)
Type of potassium channels on medium spiny neurons , what’s the significance?
potassium inward rectifiers
Keep MSNs quiet and they require the simultaneous stimulation from several excitatory inputs (both glutamatergic cortical and DA substantia nigra inputs) to become activated.
When do MSNs fire? How does this correlate to the function of specific striatum areas?
- in anticipation of an impending movement
- precedes subsequent movement by intervals in the 100s of milliseconds range although activity can precede movement by several seconds
- indicates that striatum neurons play a role in selection/decision of appropriate movements and not other motor behavior elements (eg direction or amplitude)
Putamen: fires in anticipation of limb or trunk movement
Caudate: fires in anticipation of eye movements
Where do MSNs project to? What NT do they release?
GABAergic
project to both the internal and external globus pallidus (GP) and to the substanstia nigra pars reticulata (SN-R)
What is unique about the projections from the striatum to the GP and SN-R?
Substantial amount of convergence of input from the striatum (100 million neurons) to the GP and SN-R (700,000 neurons), but the pattern of innervation is unusual:
striatal MSNs weakly innervate many targets and strongly innervate one target.
Where does the GPi project?
thalamic targets which then project to the motor cortex
Where does the SN-R project to?
superior colliculus (eye movements)
What’s unique about GPi neurons?
GABAergic
tonically active
innervated by MSNs, target thalamus which they constantly inhibit
The thalamus has excitatory neurons that project to the motor cortex.
What happens when MSNs are activated?
they inhibit the inhibitory neurons in the GP-internal (disinhibition)
this removes the inhibition onto the thalamic neurons, allowing these excitatory neurons to stimulate their targets in the motor cortex
referred to as gating a movement.
Describe the steps in basal ganglia disinhibition and the generation of saccadic eye movements.
- Caudate is activatived, increases activity.
- This results in the SN-r inhibition
- The superior colliculus is active as a result of the disinhibition
- Motor behavior is generated! (eye movement)
Describe the basal ganglia disinhibition and generation of limb/body movements.
Putamen is activated
GP-i is therefore inhibited
This allows the thalamus to be active as a result of disinhibition
Motor behavior is generated!!
Direct pathway diagram
Cerebral cortex stimulates Cuadate/putamen
(substantia nigra pars compacta has positive D1 inputs to caudate/putamen to increase likelihood of appropriate motor action)
Caudate/putamen signal to GPi, which inhibits its activity
Inhibited GPi allows the thalamus to be disinhibited
thalamus stimulates frontal cortex for limb/trunk movement.
What is the indirect pathway?
involves the GP-e which has a tonic negative influence on the subthalamic nucleus
subthalamic nucleus stimulates GPi
overall, opposes the action of the direct pathway.
Note: Sn-C has D2 projections to the caudate/putamen areas associated with the indirect pathway and therefore make it harder for this pathway to fire.
What does the direct pathway ultimately result in?
the direct pathway ultimately results in the activation of thalamic neurons that lead to the initiation of specific behaviors. That is, it is gating the expression of the desired behavior.
What does the indirect pathway ultimately do?
The indirect pathway between striatum and the GP-external, however, opposes the actions of the direct pathway. It does this by modulating the disinhibitory signaling of the direct pathway.
How does activation of striatum MSNs contribute to the indirect pathways? (GP-e)
Activation of striatum MSNs (by the cerebral cortex) inhibits tonically-active inhibitory neurons on the GP-external that project to the subthalamic nucleus.
This causes a disinhibition of excitatory (glutamatergic) neurons in the subthalamic nucleus
At the same time, cortical excitatory input also stimulate subthalamic nucleus neurons
The resulting activation of the excitatory subthalamic neurons stimulates the inhibitory neurons in the GP-internal, increasing their inhibitory output to the thalamus and thereby suppressing initiation of motor behaviors.
Describe the gate-controlling roles of the direct and indirect pathway of the basal ganglia.
So, the basal ganglia are like a gate controlling the initiation of motor behaviors with the direct and indirect pathways having opposing actions on the gate.
Direct pathway decreases inhibitory output to the thalamus, allowing initiation of motor behaviors.
Indirect pathway increases inhibitory output to the thalamus, suppressing initiation of motor behaviors.
Describe what is meant by center-surround and how the basal ganglia pathways may be viewed as a center-surround system.
- It is thought that the direct and indirect pathways are organized into center-surround structure to control the selection of the proper motor behavior.*
- That is, activate the desired behavior and suppress competing, but inappropriate behaviors.*
This is accomplished by the fact that the output of the direct pathway is focused to specific functional units,
- (physiologically, a result of striatum have strong synaptic input to a single target neuron in the GP-internal)
…whereas the output of the indirect pathway is more diffuse, inhibiting many functional units.
- (a result of subthalamic input activating multiple neurons in the GP-internal at more or less equivalent levels)
Exactly how the appropriate direct vs. indirect pathways are activated by cortical input is unclear.
Center-surround basal ganglia system- in short!
focuses behavior, suppresses the similar but unnecessary pathways via indirect pathway.
How could dopamine modulation have anything to do with the basal ganglia?
Dopaminergic neurons from the substantia nigra pars compacta (SN-c) innervate the striatum, but have different effects on the direct and indirect pathways.
SN-c inputs to striatal MSNs that project to the GP-internal (direct pathway) are excitatory:
- D1 receptors on these MSNs
SN-c inputs to “ “ that project to the GP-e (indirect path) are inhibitory:
- D2 receptors
- inhibit cAMP production; inhibit activity of MSNs
Substantia nigra pars compacta axons synapse where? What do they do?
dendritic shafts of the MSN dendrites in the GPi and GPe
electrically down stream of cortical inputs to the MSNs which are on the dendritic spines
This means that they are in a good position ot suppress EPSPs propagating from the dendritic spines to the MSN soma/initiation site
What is the net influence of DA on the basal ganglia?
Despite the different effects of DA on the two pathways, the net influence of DA is to decrease the inhibitory influence of the basal ganglia on thalamocortical circuits
Enhance activity in the direct pathway leads to greater disinhibition of the GP-internal
Suppress activity in the indirect pathway leads to weaker stimulation of the GP-internal by the subthalamic nucleus
Prefrontal basal ganglia loop
Involved in the regulation of attention & cognitive planning.
Tourette’s syndrome may reflect a disregulation of speech centers in the prefrontal cortex.
Limbic basal ganglia loop
Involved in regulation of emotional and motivation states. May also match goal-directed motor behaviors to a specific emotional “valence” (good/bad).
Dysfunction of limbic loop may contribute to addiction and to schizophrenia.
Non-motor basal ganglia loops
In addition to the motor circuits just discussed there are non-motor loops that are associated with a variety of functions and pathologies.
The function of these non-motor loops may be analogous to the role that the basal ganglia play in the motor loops; that is, the gating of some function.
Includes prefrontal and limbic loops
