RT Journal Article
SR Electronic
T1 Effects of early life stress and subsequent re-exposure to stress on neuronal activity in the lateral habenula
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.08.11.503558
DO 10.1101/2022.08.11.503558
A1 Jack F. Webster
A1 Sanne Beerens
A1 Christian Wozny
YR 2022
UL http://biorxiv.org/content/early/2022/08/11/2022.08.11.503558.abstract
AB Early life stress can result in depression in humans and depressive-like behaviour in rodents. In various animal models of depression, the lateral habenula (LHb) has been shown to become hyperactive immediately after early life stress. However, whether these pathological changes persist into adulthood is less well understood. Hence, we utilised the maternal separation (MS) model of depression to study how early life stress alters LHb physiology and depressive behaviour in adult mice. We find that only a weak depressive phenotype persists into adulthood which surprisingly is underpinned by LHb hypoactivity in acute slices, accompanied by alterations in both excitatory and inhibitory signalling. However, while we find the LHb to be less active at rest, we report that the neurons reside in a sensitised state where they are more responsive to re-exposure to stress in adulthood in the form of acute restraint, thus priming them to respond to aversive events with an increase in neuronal activity mediated by changes in glutamatergic transmission. These findings thus suggest that in addition to LHb hyperactivity, hypoactivity likely also promotes an adverse phenotype. Re-exposure to stress results in the reappearance of LHb hyperactivity offering a possible mechanism to explain how depression relapses occur following previous depressive episodes.Competing Interest StatementThe authors have declared no competing interest.