Figure 1.

Nigrostriatal, mesocortical, and mesolimbic pathways. When cortical neurons activate the NMDA receptors on neurons of the direct pathway (red) in the striatum, striatal neurons are primed to send GABA signals to the SNr/GPi, which would inhibit the tonic GABA to the thalamus, allow glutamate signals to fire in the cortex, and further activate cortical neurons. The indirect pathway (blue) is primed when cortical neurons activate the NMDA receptors on the striatal neurons that express D₂ receptors, which would send inhibitory signals to the globus pallidus externa (GPe), reduce GABA signaling to the STN, and stimulate the SNr/GPi to enhance GABA inhibiting of thalamocortical signaling. The mesolimbic pathway (green) consist of dopaminergic projections from the VTA to the NAcc, which sends inhibitory signals to the SNr/GPi. The mesocortical pathway (orange) consists of dopaminergic projections from the VTA to the cortex, innervating both pyramidal and non-pyramidal neurons which express D₁ receptors. Reciprocal pathways (purple) from the cortex to the VTA and NAcc provide cortical feedback to subcortical structures. CTX, cortex; GABA, gamma-aminobutyric acid; NMDA, N-methyl-D-aspartate; GPe, globus pallidus externa; SNr, substantia nigra pars reticulata; GPi, globus pallidus interna; TH, thalamus; STN, sub thalamic nucleus; NAcc, nucleus accumbens core; VTA, ventral tegmental area. Round structures indicate dopamine cell bodies; star shaped structures indicate GABA cell bodies; triangular structures indicate glutamate cell bodies.