Lecture 16: Basal Ganglia and Cerebellum Flashcards
Because the efferent cells of both the globus pallidus and substantia nigra pars reticulata are GABAergic, the main output of the basal ganglia is inhibitory. In contrast to the quiescent medium spiny neurons, the neurons in both of these output structures have high levels of spontaneous activity that prevent unwanted movement by tonically inhibiting cells in the thalamus and superior colliculus. Because the medium spiny neurons of the striatum also are GABAergic and inhibitory, the net effect of the phasic excitatory inputs that reach the striatum from the cortex is to open a physiological gate by inhibiting the tonically active inhibitory cells of the globus pallidus and substantia nigra pars reticulata.
Inhibition/excitation in basal ganglia loops - overview
When the eyes are fixating a visual target, these upper motor neurons are toni-cally inhibited by the spontaneously active reticulata cells, thus preventing unwanted saccades. Shortly before the onset of a saccade, the tonic discharge rate of the reticulata neurons is sharply reduced by input from the GABAergic medium spiny neu- rons of the caudate, which have been activated by signals from the cortex. The subsequent reduction in the tonic discharge from reticulata neurons disinhibits the upper motor neurons of the superior colliculus, allowing them to generate the bursts of action potentials that command the saccade.
Thus, 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 sen- sory or other higher order signals from cognitive centers to activate the upper motor neurons and initiate a saccade.
The graph shows the temporal rela- tionship between inhibition in the substantia nigra pars reticulata (purple) and disin- hibition in the superior colliculus (light blue) preceding a saccade to a visual target.
Direct pathway
Indirect and direct pathway
tonic vs transient firing
tonic firing refers to a sustained response, which activates during the course of the stimulus; while phasic firing refers to a transient response with one or few action potentials at the onset of stimulus followed by accommodation.
A concept called focused selection has increased understanding of this antagonistic interaction. According to this concept, the direct and indirect pathways are functionally organized in a center–surround fashion within the output nuclei of the basal ganglia. The influence of the direct pathway is tightly focused on particular functional units in the internal segment of the globus pallidus (and the substantia nigra pars reticulata), whereas the influence of the indirect pathway is much more diffuse, covering a broader range of functional units.
Integration of cortical input by the striatum leads to the activation of the direct and indirect pathways. With activation of the indirect pathway, neurons in a “surround” region of the internal segment of the globus pallidus are driven by excitatory inputs from the sub- thalamic nucleus; this reinforces the suppression of a broad set of competing motor programs. Simultaneously, activation of the direct pathway leads to the focal inhibition of a more re- stricted “center” cluster of neurons in the internal segment; this in turn results in the disinhibition (bottom arrow) of the VA/VL complex and the expression of the intended motor program.
Degeneration of dopaminergic neurons reduces voluntary movement in Parkinson’s disease
In the midbrain of an individual with Parkinson’s disease, the substantia nigra (pigmented area) is largely absent in the region above the cerebral peduncles. The midbrain from an individual without Parkinson’s disease shows intact substantia nigra (cf. regions indicated with red arrows).
Parkinson’s disease - hypokinetic
In Parkinson’s disease, the dopaminergic inputs provided by the substantia nigra pars compacta are diminished (dashed arrows), making it more difficult to generate the transient inhibition from the caudate and putamen. The result of this change in the direct pathway is to sustain or increase the tonic inhibition from the internal segment of the globus pallidus to the thalamus (thicker arrow than corresponding arrow in Figure 18.7B), making thalamic excitation of the motor cortex less likely (thinner arrow from thalamus to frontal cortex).
Huntington’s disease - degeneration of medium spiny neurons
Increases involuntary movement. The size of the caudate and putamen (the striatum) is dramatically reduced in patients with advanced Huntington’s disease.
Huntington’s disease - hyperkinetic
In Huntington’s disease, the projection from the cau- date and putamen to the external segment of the globus palli- dus is diminished (dashed arrow). This effect increases the tonic inhibition from the globus pallidus to the subthalamic nucleus (thicker arrow), making the excitatory subthalamic nucleus less effective in opposing the action of the direct pathway (thinner arrow). Thus, thalamic excitation of the cortex is increased (thicker arrow), leading to the expression of unwanted motor activity.
Function of basal ganglia - overview
Initiation and coordination movement.
Action-selection. Behaviour exclusion. Focused election of behaviour - behavioural contrast. Big funnel.
Reinforcement learning - reward prediction error - control theory.
Personality (volition?)
Memory?
Emotions?
Subdivision of cerebellum
Functional organisation of cerebral outputs
Somatotopic maps of the body surface in the cerebellum.
The somatosensory input is topographically mapped in the spinocerebellum, providing the basis for orderly representations of the body within the cerebellum (Figure 19.4). However, these maps are “fractured”; that is, fine- grain electrophysiological analysis indicates that each small area of the body is represented multiple times by spatially separated clusters of cells, rather than by a spe- cific site within a single continuous somatotopic map. The spinocerebellum contains at least two maps of the body.
Neurons and circuits of the cerebellum
Neuronal types in the cerebellar cortex. Note that the various neuron classes are found in distinct layers.
The Purkinje cells (Figure 19.8A) are the most distinctive histological feature of the cerebellum. Their elaborate den- drites extend into the molecular layer from a single subja- cent layer of giant Purkinje cell bodies (called the Purkinje cell layer; Figure 19.8B). In the molecular layer, the Purkinje cell dendrites branch extensively but in a plane restricted at right angles to the trajectory of the parallel fibers (Figure 19.9A). In this way, each Purkinje cell is in a position to receive input from a large number of parallel fibers (about 200,000), and each parallel fiber can contact a vast number of Purkinje cells (on the order of tens of thousands). The Purkinje cells also receive a direct input on their dendritic hafts from climbing fibers, all of which arise in the con- tralateral inferior olive (Figure 19.9B). Each Purkinje cell receives numerous synaptic contacts from a single climbing fiber. The climbing fibers provide a “training” signal that modulates the synaptic strength of the parallel fiber con- nection with the Purkinje cells.
Different neurons and circuits of the cerebellum
Excitatory and inhibitory connections of cerebellar cortex and deep cerebellar nuclei
(B) - The deep cerebellar nuclei and their excitatory afferents con- stitute a deep excitatory loop whose output is shaped by a cortical inhibitory loop that inverts the “sign” of the input signals. The Purkinje neuron output to the deep cerebel- lar nuclear cell thus generates an error cor- rection signal that can modify movements. The climbing fibers modify the efficacy of the parallel fiber–Purkinje cell connection, producing long-term changes in cerebellar output
The Purkinje cells project in turn to the deep cerebellar nuclei and comprise the only output cells of the cerebel- lar cortex. Since Purkinje cells are GABAergic, the output of the cerebellar cortex is wholly inhibitory. However, the neurons in the deep cerebellar nuclei also receive excitatory input from the collaterals of the mossy and climbing fibers. The inhibitory projections of Purkinje cells serve to sculpt the discharge patterns that deep nuclei neurons generate in response to their direct mossy and climbing fiber inputs (Figure 19.10).
Mossy fiber and climbing fiber collater- als drive the activation of neurons in the deep cerebellar nuclei; this constitutes a deep excitatory loop in which input signals converge on the final output stage of cerebellar processing.
The response patterns of the deep cerebellar nuclei to their direct inputs are modi- fied by the descending inhibitory inputs of Purkinje cells, which are driven by these same two afferent pathways (i.e., the mossy and climbing fiber projections to the cerebellar cortex). For their part, Purkinje cells integrate these prin- cipal inputs and invert their “sign” by responding to excit- atory inputs with an inhibitory output (see Figure 19.10B). Thus, Purkinje cells convey the product of computations performed by a cortical inhibitory loop that comprises the circuitry of the cerebellar cortex, including the interneu- rons of the granule and molecular layers, as well as the Purkinje cells themselves.
Ataxia with cerebellar damage
Smooth execution of a visually guided reach in an individual with typical cerebellum function. (B) Poorly coordinated visually guided reach (appendicular ataxia) in an individual with cerebellar damage. The hand takes a much less straight trajectory to the target, with irregular movements that typically overshoot or undershoot the visual target and so require frequent corrective movements to exe- cute the intended motor task.
Lesions in cerebellar cortex
