Lateral Septum Somatostatin Neurons are Activated by Diverse Stressors

The lateral septum (LS) is a forebrain structure that has been implicated in a wide range of behavioral and physiological responses to stress. However, the specific populations of neurons in the LS that mediate stress responses remain incompletely understood. Here, we show that neurons in the dorsal lateral septum (LSd) that express the somatostatin gene (hereafter, LSd(Sst) neurons) are activated by diverse stressors. Retrograde tracing from LSd(Sst) neurons revealed that these neurons are directly innervated by neurons in the locus coeruleus (LC), the primary source of norepinephrine well-known to mediate diverse stress-related functions in the brain. Consistently, we found that norepinephrine increased excitatory synaptic transmission onto LSd(Sst) neurons, suggesting the functional connectivity between LSd(Sst) neurons and LC noradrenergic neurons. However, optogenetic stimulation of LSd(Sst) neurons did not affect stress-related behaviors or autonomic functions, likely owing to the functional heterogeneity within this population. Together, our findings show that LSd(Sst) neurons are activated by diverse stressors and suggest that norepinephrine released from the LC may modulate the activity of LSd(Sst) neurons under stressful circumstances.