Aberrant cortical projections to amygdala GABAergic neurons contribute to developmental circuit dysfunction following early life stress

Joni Haikonen; Jonas Englund; Shyrley Paola Amarilla; Zoia Kharybina; Alexandra Shintyapina; Kristel Kegler; Marta Saez Garcia; Tsvetomira Atanasova; Tomi Taira; Henrike Hartung; Sari E Lauri

doi:10.1016/j.isci.2022.105724

Aberrant cortical projections to amygdala GABAergic neurons contribute to developmental circuit dysfunction following early life stress

iScience. 2022 Dec 5;26(1):105724. doi: 10.1016/j.isci.2022.105724. eCollection 2023 Jan 20.

Authors

Joni Haikonen^{1

2}, Jonas Englund², Shyrley Paola Amarilla^{2

3}, Zoia Kharybina^{1

3}, Alexandra Shintyapina², Kristel Kegler³, Marta Saez Garcia¹, Tsvetomira Atanasova³, Tomi Taira³, Henrike Hartung¹, Sari E Lauri^{1

2}

Affiliations

¹ HiLife Neuroscience Center, University of Helsinki, Helsinki, Finland.
² Molecular and Integrative Biosciences Research Program, University of Helsinki, Helsinki, Finland.
³ Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.

Abstract

Early life stress (ELS) results in enduring dysfunction of the corticolimbic circuitry, underlying emotional and social behavior. However, the neurobiological mechanisms involved remain elusive. Here, we have combined viral tracing and electrophysiological techniques to study the effects of maternal separation (MS) on frontolimbic connectivity and function in young (P14-21) rats. We report that aberrant prefrontal inputs to basolateral amygdala (BLA) GABAergic interneurons transiently increase the strength of feed-forward inhibition in the BLA, which raises LTP induction threshold in MS treated male rats. The enhanced GABAergic activity after MS exposure associates with lower functional synchronization within prefrontal-amygdala networks in vivo. Intriguingly, no differences in these parameters were detected in females, which were also resistant to MS dependent changes in anxiety-like behaviors. Impaired plasticity and synchronization during the sensitive period of circuit refinement may contribute to long-lasting functional changes in the prefrontal-amygdaloid circuitry that predispose to neuropsychiatric conditions later on in life.

Keywords: Behavioral neuroscience; Developmental neuroscience; Systems neuroscience.