Notes

Basal Ganglia:
The Basal Gangia plays a role in action selection and initiation of movement. The cortex and basal ganglia form a processing loop, cortex reiays desired motor output and the proper motor programs are selected and initiated by the basal ganglia. It selects the desried motor program while inhibiting competing programs.

The basal ganglia is composed of 4 subcortical structures:
- striatum: major input structure of basal ganglia, receives input from cortex, brain stem, and thalamus
- globus pallidus: made up of the internal segment (GPi) - one of the major output structures of the basal ganglia andd the external segment (GPe) - part of the intrinsic circuitry
- The substantia nigra: made of pars compacta which contain dopaminergic cells that project to the striatum and the pars reticulata (major output structure of BG)
- The subthalmatic nucleus: receives projections from GPe, cortex, thalamus, and brainstem and sends output to Gpe, GPi, and SNr

Direct pathway: results in activation of desired motor program
- excitatory glutamatergic projections sent to the striatum, stimulating GABAergic medium spiny neurons (MSN) that project to GPi
- GPi contains inhibitory GABA cells that project to thalamus. GPi neurons are tonically active at rest, placing a break on the thalamus
- MSN inhibit the inhibitory activity of GPi, stimulating activity, increasing excitatory input from thalamus to cortex
Striatal medium spiny neurons have an abundance of spines and dendrites. 90% of cells in striatum

Indirect pathway: inhibition of undesired, competing motor programs
- multiple cortical regions send excitatory glutamatergic projections to the striatum, activating a different population of GABAergic MSNs in striatum which project to GPe. GPe contains inhibitory GABA cells which are tonically active at rest.
- MSN inhibit the inhibitory activity of GPe neurons, releasing the break on GPi that inhibits thalamus, STN excitatory projections to GPi which activate GPi and inhibit thalamus, STN excitatory projections to SNr which inhibit thalamus.

Glutamate is an excitatory neurotransmitter and dopamine is a modulatory neurotransmitter. Glutamatergic inputs from cortex and dopaminergic inputs fro SNc terminate on dendritic spines of MSNs. Dopamine modulates the strength of cortical input. D1 dopamine receptors will depolarise the cell in response to dopamine. D2 receptors will hyperpolarize the cell in response, decreasing strength of cortical input

Dopamine pathway: ensures no inhibition of desired motor program and inhibition of competing program
- excitatory glutamatergic projections to striatum. Direct pathway MSNs express D1 dopamine receptors, while indirect pathway MSNs express D2 receptors.
- Nigrostriatal pathway increases strength of cortical input in direct and decreases strength in indirect

Parkinson's disease: loss of dopaminergic neurons in SNc, resulting in in ability to move, slowness, muscular rigidity, resting tremor. Dopaminergic receptors appear black in normal humans.
- Loss of SNc Dopa neurons results in increase in activity of indirect pathway, and decrease in direct pathway, inhibitory outflow of BG is abrnomally high and timely thamatic activation of upper motor neurons is less likely
- treated with L-dopa (precursor to dopamine) or deep brain stimulation to augment thalamocortical activation.

Huntington's Disease: loss of GABAergic MSNs in striatum (particularly in indirect path) caused by mutation in gene that codes for huntingtin protein resulting in abnormal involuntary movements
- loss of MSNs in striatum that project to GPe, GPe becomes abnormally active, reduces output of STN to GPi and reduces inhibitory outflow of basal ganglia. No supressio of competing motor programs