A differential and timed contribution of identified hippocampal synapses to associative learning in mice

Although it is generally assumed that the hippocampus is involved in associative learning, the specific contribution of the different sy-napses present in its intrinsic circuit or comprising its afferents and efferents is poorly defined. We studied here activity-dependent changes in synaptic strength of 9 hippocampal synapses (corre-sponding to the intrinsic hippocampal circuitry and to its main inputs and outputs) during the acquisition of a trace eyeblink conditioning in behaving mice. The timing and intensity of synaptic changes across the acquisition process was determined. The evolution of these timed changes in synaptic strength indicated that their func-tional organization did not coincide with their sequential distribution according to anatomical criteria and connectivity. Furthermore, we explored the functional relevance of the extrinsic and intrinsic affer-ents to CA3 and CA1 pyramidal neurons, and evaluated the distinct input patterns to the intrinsic hippocampal circuit. Results confirm that the acquisition of a classical eyeblink conditioning is a multisy-naptic process in which the contribution of each synaptic contact is different in strength, and takes place at different moments across learning. Thus, the precise and timed activation of multiple hippo-campal synaptic contacts during classical eyeblink conditioning evokes a specific, dynamic map of functional synaptic states in that circuit