Corticotropin-releasing factor induces functional and structural synaptic remodelling in acute stress

Dorien Vandael,Vasily Rybakin,Lieve Moons,Pieter Baatsen,Lies De Groef,Keimpe Wierda,Katlijn Vints,Natalia V Gounko

doi:10.1038/s41398-021-01497-2

Abstract

Biological responses to stress are complex and highly conserved. Corticotropin-releasing factor (CRF) plays a central role in regulating these lifesaving physiological responses to stress. We show that, in mice, CRF rapidly changes Schaffer Collateral (SC) input into hippocampal CA1 pyramidal cells (PC) by modulating both functional and structural aspects of these synapses. Host exposure to acute stress, in vivo CRF injection, and ex vivo CRF application all result in fast de novo formation and remodeling of existing dendritic spines. Functionally, CRF leads to a rapid increase in synaptic strength of SC input into CA1 neurons, e.g., increase in spontaneous neurotransmitter release, paired-pulse facilitation, and repetitive excitability and improves synaptic plasticity: long-term potentiation (LTP) and long-term depression (LTD). In line with the changes in synaptic function, CRF increases the number of presynaptic vesicles, induces redistribution of vesicles towards the active zone, increases active zone size, and improves the alignment of the pre- and postsynaptic compartments. Therefore, CRF rapidly enhances synaptic communication in the hippocampus, potentially playing a crucial role in the enhanced memory consolidation in acute stress.

Highlights

Stress is a fundamental homeostatic reaction to any stimulus [1, 2], which can biologically manifest itself as predominantly positive ‘eustress’ or negative ‘distress’ [3]
15 min prior to the start of and throughout the recordings, we. Both short-term stress and Corticotropin-releasing factor (CRF) treatment induce spine showed a robust increase in miniature excitatory postsynaptic currents (mEPSCs) frequency, but not amplitude formation in vivo (Fig. 3a–e)
We observed for acute, mild stress in mice expressing YFP in CA1 pyramidal cells (PC): foot ultrastructural changes within synapses, which are in line with shock (FS) and predator odor (PO)

Summary

Introduction

Stress is a fundamental homeostatic reaction to any stimulus [1, 2], which can biologically manifest itself as predominantly positive ‘eustress’ or negative ‘distress’ [3]. Mild or short stress enhances hippocampal functioning by promoting synaptic strengthening and by augmenting frequency of miniature excitatory postsynaptic currents (mEPSCs) and glutamate release probability [7, 19], while profound and chronic stress has detrimental effects, manifesting in the reduction in dendritic complexity and spine density in the hippocampus [12]. This spine loss is associated with attenuation of both LTP and LTD, and correlates with reported memory defects [7, 20, 21]. Short-term CRF application increases LTP [26] while prolonged exposure impairs hippocampal LTP [27]

Methods

Results

Conclusion