Substantia nigra modulates breathing rate via locus coeruleus

Breathing is an automatic and rhythmic act primarily controlled by hindbrain neural circuits, including the pre-Bötzinger complex. While the basal ganglia are known to regulate a wide range of behaviors through downstream projections, their role in breathing control remains unclear. In this study, we demonstrate that outputs from the substantia nigra (SN) can modulate breathing rate in a cell-type specific manner. Specifically, optogenetic activation of glutamic acid decarboxylase 2 (Gad2)-expressing neurons in the SN, but not parvalbumin (Pvalb)-expressing neurons, decreased breathing rate in lightly anesthetized mice. Importantly, this effect was mediated through the inhibition of neural activity in the locus coeruleus (LC), suggesting a relationship between the decrease in breathing rate and the baseline firing rate of LC neurons. These findings provide evidence that the basal ganglia play an important role in the control of breathing rate through modulation of LC neural activity.