Basal ganglia function Domina Petric, MD

Disinhibition in the body movement loop: direct and indirect basal ganglia pathways

Disinhibition Disinhibition is inhibition of the inhibition. Two inhibitory neurons are connected with each other. Striatal neuron is recieving excitatory inputs from cerebral cortex. Striatal neuron releases inhibitory neurotransmitter on the globus pallidus neuron. Globus pallidus neuron is releasing inhibitory neurotransmitter on the thalamic neuron when there is no striatal activity.

Disinhibition (direct basal ganglia pathway) Striatal neuron shuts the inhibitory activity of the globus pallidus neuron on the thalamic neuron. Thalamic neuron then releases excitatory neurotransmitter for cortical target. In the motor loop, cortical target is motor cortex. Motor cortex creates action potential that is generated down the corticospinal tract.

Disinhibition in the direct pathway of the basal ganglia Transient excitatory inputs from cortex Motor cortex Striatal neuron inhibits inhibitory globus pallidus neuron. Globus pallidus is inhibitory neuron connected with thalamic neuron. Globus pallidus neuron Thalamic neuron Striatal neuron Striatal neuron inhibits the globus pallidus neuron. Inhibition of thalamic neuron is inhibited and thalamic neuron from VA-VL thalamic nuclei complex sends excitatory input to the motor cortex.

Disinhibition (direct pathway) The inhibitory activity of the globus pallidus internal segment is high when striatum is at rest: inhibition of VA-VL thalamic complex. When striatal neuron is activated, there is no inhibitory activity of the globus pallidus internal segment: excitation of VA-VL thalamic complex. Thalamus is disinhibited: released from inhibition.

Indirect basal ganglia pathway Indirect basal ganglia pathway that includes subthalamic nuclei, reinforces the tonic inhibition of VA-VL thalamic nuclei complex. Activation of striatal neuron causes inhibitory input to the external segment of the globus pallidus. Globus pallidus external segment inhibitory neuron is inhibited. Subthalamic nucleus is disinhibited: released from inhibition. Subthalamic nucleus causes then excitation of globus pallidus internal segment neron that inhibits the thalamic neuron.

Dopamine function in basal ganglia D1 receptors + dopamine = increase of cAMP levels, excitation D2 receptors + dopamine = decrease of cAMP levels, inhibition Dopamine is a key regulator of the responsiveness of the postsynaptic neuron to the input from the cortex. D1 receptors are expressed by neurons of the striatum that are in direct pathway of the basal ganglia. D2 receptors are expressed by neurons of the striatum that are in indirect pathway of the basal ganglia.

Dopamine function in basal ganglia When dopamine binds to D1 receptors, direct pathway is activated: movement is facilitated. When dopamine binds to D2 receptors, indirect pathway is activated and there is no movement.

Basal ganglia function overview Striatal neurons fire before and during movement onset. Basal ganglia play a role in initiating and terminating the movement onset. Balance of activity in direct and indirect pathways mediates the initiation and suppression of movement.

Movement disorders II.

Parkinsonism akinesia/bradykinesia rigidity resting tremor reduced facial expressions shuffling gate difficulty with initiating and terminating movements cognitive changes, dementia

Parkinsonism Loss of dopamine producing neurons in Substantia nigra, pars compacta. Clinical presentation begins when there is loss of 75-80% of dopaminergic neurons. There is no facilitation of the direct pathway and no supression of the indirect pathway: tonic inhibition of thalamus, bradykinesia or akinesia.

Huntington disease involuntary choreic (like dance) movements, hyperkinesia severe dementia onset in fourth or fifth decade of life CAG repeats in Huntington gene are too high (more than 20) neuronal degeneration of medium spiny neurons of the striatum that express D2 receptors (loss of indirect pathway, no supression of movement)

Literature https://www.coursera.org/learn/medical-neuroscience/lecture: Leonard E. White, PhD, Duke University