Effects of early life stress and subsequent re-exposure to stress on neuronal activity in the lateral habenula

Jack F. Webster, Sanne Beerens, Christian Wozny

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)745-753
JournalNeuropsychopharmacology
Volume48
Issue number5
DOIs
Publication statusPublished - 1 Apr 2023
Externally publishedYes

Funding

This work was funded by an EPSRC Doctoral Prize to JFW, a NARSAD Young Investigator Award to CW (Grant number 28217, named P&S Fund Investigator) and by the European Union’s Horizon 2020 Research and Innovation Program under Grant Agreement No. ICT-36-2020-101016787, DEEPER to CW.

FundersFunder number
National Alliance for Research on Schizophrenia and Depression28217
Horizon 2020 Framework ProgrammeICT-36-2020-101016787
Engineering and Physical Sciences Research Council

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