Differential short-term plasticity at convergent inhibitory synapses to the substantia nigra pars reticulata

Inhibitory projections from the striatum and globus pallidus converge onto GABAergic projection neurons of the substantia nigra pars reticulata (SNr). Based on existing structural and functional evidence, these pathways are likely to differentially regulate the firing of SNr neurons. We sought to investigate the functional differences in inhibitory striatonigral and pallidonigral traffic using whole-cell voltage clamp in brain slices with these pathways preserved. We found that striatonigral IPSCs exhibited a high degree of paired-pulse facilitation. We tracked this facilitation over development and found the facilitation as the animal aged, but stabilized by postnatal day 17 (P17), with a paired pulse ratio of 2. We also found that the recovery from facilitation accelerated over development, again, reaching a stable phenotype by P17. In contrast, pallidonigral synapses show paired-pulse depression, and this depression could be solely explained by presynaptic changes. The mean paired-pulse ratio of 0.67 did not change over development, but the recovery from depression slowed over development. Pallidonigral IPSCs were significantly faster than striatonigral IPSCs when measured at the soma. Finally, under current clamp, prolonged bursts of striatal IPSPs were able to consistently silence the pacemaker activity of nigral neurons, whereas pallidal inputs depressed, allowing nigral neurons to reinstate firing. These findings highlight the importance of differential dynamics of neurotransmitter release in regulating the circuit behavior of the basal ganglia.