Footshock-induced responses in ventral subiculum neurons are mediated by locus coeruleus noradrenergic afferents

Abstract

The ventral subiculum (vSub) of the hippocampus is critically involved in mediating the forebrain's response to stress, particularly with regard to psychogenic stressors. Stress, in turn, is known to aggravate many psychiatric conditions including schizophrenia, depression, anxiety, and drug abuse. Pathological alterations in hippocampal function have been identified in all these disorders; thus, it is of interest to understand how stress affects this brain region. The vSub receives dense projections from the stress-related locus coeruleus (LC); however, it is not known what role this input plays in signaling stressful stimuli. In this study, the direct LC innervation of the vSub was investigated as a potential mediator of stress responses in this region. To examine responses to an acute stressor, the effect of footshock on single vSub neurons was tested in rats. Footshock inhibited 13%, and activated 48% of neurons in this region. Importantly, responses to footshock were correlated with LC stimulation-evoked responses in single neurons, and LC inactivation blocked these responses. Furthermore, prazosin, an alpha-1 antagonist, reversed footshock-evoked inhibition, revealing an underlying activation. Inactivation of the basolateral amygdala (BLA) did not block phasic footshock-evoked activation; however, it reduced tonic activity in the vSub. These results suggest that the LC NE system plays an important role in mediating stress responses in the vSub. Footshock evokes both inhibition and excitation in the vSub, by activating noradrenergic inputs from the LC. These responses may contribute to stress adaptation; while an imbalance of this system may lead to pathological stress responses in mental disorders.