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The direct pathway, as in response to striatal MSN activation, there is inhibition of the SNr shown in B and C. This inhibition via GABAergic synapses results in the thalamus being disinhibited, which increases the excitability of the cortex, therefore facilitating movement.

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GPe

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Illumination induced partial immobilization of mice at the time of illumination, followed by immediate movement recovery after illumination but leading to an overall decrease in movement over time.

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Illumination induced partial immobilization of mice at the time of illumination, followed by immediate movement recovery after illumination but leading to an overall decrease in movement over time.

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Disinhibition of STN leads to activation of the output nuclei, increased inhibition of the thalamus and a decrease in cortex activity and movement.

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ChR2 stimulation of cell type Y reduced the time spent immobile. Percentage time spent immobile decreased after each ChR2 stimulation of cell type Y.

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After stimulation of ChR2-GFP the time immobile decreased, and then recovers. Showing that the activation of these neurons leads to a decrease in movement.

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If it synapsed onto the SNpr then this would cause inhibition of thalamus, decreased activation in cortex and decreased movement. However, we have found that there is an increased in movement therefore it must synapse onto cell type X

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Visualise using fluorescence microscopy the YFP fluorescence in the medium spiny neuron cell body in the striatum as well as in the output nuclei: GPi and SNr, but NOT in the medium spiny neurons which express D2 dopamine receptors in the external segment of the globus pallidus (GPe)

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You could fuse YFP to the channelrhodopsin-2 protein, and confirm its expression using fluorescent microscopy. You would expect to see fluorescence in the striatum, and the output nuclei.

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You would insert an electrode into the striatum in vivo and a probe which shines a blue light into the striatum. You would expect to record action potentials as a result of the blue light opening the channelrhodpsin-2 depolarising the cell.

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We could visualize YFP fluorescence, which should be restricted to the striatum, the internal segment of the globus pallidus and the SNr.

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We could visualize YFP fluorescence, which should be restricted to the striatum, the internal segment of the globus pallidus and the SNr.

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You could visualise the fluorescence and see if it is in the correct locations (striatum, internal segment of the globulus pallidus, and the substantia nigra pars reticulata). Then you could shine a blue light onto it, if there is a robust increase in the striatum action potential firing