Corticotropin-Releasing Factor Induces Functional And Structural Synaptic Remodelling In Acute Stress

Biological responses to internal and external stress factors involve highly conserved mechanisms, using a tightly coordinated interplay of many factors. Corticotropin-releasing factor (CRF) plays a central role in organizing these lifesaving physiological responses to stress. We show that CRF rapidly and reversibly changes Schaffer Collateral 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 Schaffer collateral input into CA1 neurons, e.g. increase in spontaneous neurotransmitter release, paired-pulse facilitation and repetitive excitability and improves long-term synaptic plasticity: LTP and 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 post-synaptic compartments. Together, CRF rapidly enhances synaptic communication in the hippocampus, potentially playing a crucial role in the enhanced memory consolidation in acute stress.