Somatostatin regulation of the stress response

Stressful stimuli trigger long-term alterations in brain plasticity that are associated with affective symptoms in stress-related psychiatric disorders. Somatostatin and somatostatin-expressing GABAergic neurons (SST neurons) profoundly shape the neuronal activity, synaptic plasticity, and behavior. Preclinical evidence demonstrates that stress exposure disrupts SST expression and alters the density and physiological function of SST neurons. Importantly, deficits within the somatostatinergic system are strongly correlated with various neuropsychiatric and neurodegenerative conditions in humans. Our review provides a comprehensive overview of the SST system, characterizing its receptors and functions, as well as the physiological properties and circuitry of SST neurons. We summarize the current findings on the regulatory roles of somatostatin and SST neurons in stress response at the molecular and circuitry levels. Furthermore, we review evidence for SST deficits across pathological brain conditions, focusing primarily on stress-related psychiatric disorders. Finally, we discuss the therapeutic potential of targeting the somatostatin system and outline the key questions.