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Authors & Affiliations
Hannah Klimmt, Alessandro Ulivi, David Kappel, Bhargavi Keerthana Boovaraga Murthy, Alessio Attardo
Abstract
The formation of new memories requires the hippocampus, a brain region which exhibits high levels of structural plasticity. Within the dorsal hippocampal CA1, specific interneuron subtypes synapse onto specific subcellular compartments of Pyramidal Neurons (PNs) such as dendrites, soma and axon initial segment (AIS) thus shaping the cellular computations underlying memory formation. Yet, very little is known about the long-term structural dynamics of these compartmentalized inhibitory synapses on PNs and their link to learning.To address these outstanding questions, we used longitudinal in vivo deep-brain two-photon microscopy to track inhibitory synapses for two weeks in mice performing the hippocampal-dependent memory task Trace Fear Conditioning (TFC).Our study identified notable differences in stability of inhibitory synapses across the three neuronal compartments. Specifically, soma-targeting synapses displayed a significantly higher rate of addition and loss compared to the other compartment, thus being the most unstable ones. Surprisingly, TFC training did not affect the dynamics of the most unstable inhibitory synapses but rather led to stabilization of AIS synapses with no measurable effect on somatic or dendritic synapses. Our findings shed light on the hitherto uncharacterized relationship between the structural dynamics of compartmentalized inhibitory synapses and learning in the hippocampus.