A role for GABA in the modulation of striatal and hippocampal systems under stress

Nina Dolfen,Lars Schwabe,Menno P Veldman,Mark Mikkelsen,Richard A E Edden,Geneviève Albouy,Nicolaas A J Puts,Andreas Von Leupoldt,Mareike A Gann,Bradley R King,Stephan Swinnen

doi:10.1038/s42003-021-02535-x

Abstract

Previous research has demonstrated that stress modulates the competitive interaction between the hippocampus and striatum, two structures known to be critically involved in motor sequence learning. These earlier investigations, however, have largely focused on blood oxygen-level dependent (BOLD) responses. No study to date has examined the link between stress, motor learning and levels of striatal and hippocampal gamma-aminobutyric acid (GABA). This knowledge gap is surprising given the known role of GABA in neuroplasticity subserving learning and memory. The current study thus examined: a) the effects of motor learning and stress on striatal and hippocampal GABA levels; and b) how learning- and stress-induced changes in GABA relate to the neural correlates of learning. To do so, fifty-three healthy young adults were exposed to a stressful or non-stressful control intervention before motor sequence learning. Striatal and hippocampal GABA levels were assessed at baseline and post-intervention/learning using magnetic resonance spectroscopy. Regression analyses indicated that stress modulated the link between striatal GABA levels and functional plasticity in both the hippocampus and striatum during learning as measured with fMRI. This study provides evidence for a role of GABA in the stress-induced modulation of striatal and hippocampal systems.

Highlights

Previous research has demonstrated that stress modulates the competitive interaction between the hippocampus and striatum, two structures known to be critically involved in motor sequence learning
Participants were trained on a motor sequence learning (MSL) task during fMRI (Fig. 1)
We investigated the link between STR/HC GABA+ measures and blood oxygen-level dependent (BOLD) responses in our regions of interest (ROI) and, in particular, whether this link was modulated by stress

Summary

Introduction

Previous research has demonstrated that stress modulates the competitive interaction between the hippocampus and striatum, two structures known to be critically involved in motor sequence learning These earlier investigations, have largely focused on blood oxygen-level dependent (BOLD) responses. No study to date has examined the link between stress, motor learning and levels of striatal and hippocampal gamma-aminobutyric acid (GABA) This knowledge gap is surprising given the known role of GABA in neuroplasticity subserving learning and memory. Our findings suggested that inter-subject variability in the brain responses to stress in these regions determines the impact of stress on motor learning and memory retention These prior studies provided critical insights into how learning and stress alter blood oxygen-level dependent (BOLD) responses in cortico-hippocampal and cortico-striatal networks. Reports on hippocampal and striatal regions are currently lacking

Results

Discussion

Conclusion