The viruses used from BrainVTA in this article are in the table below

Encoding specificity theory predicts most effective recall by the original conditions at encoding, while generalization endows recall flexibly under circumstances which deviate from the originals. The CA1 regions have been implicated in memory and generalization but whether and which locally separated mechanisms are involved is not clear. We report here that fear memory is quickly formed, but generalization develops gradually over 24 h. Generalization but not fear memory is impaired by inhibiting ipsilateral (ips) or contralateral (con) CA1, and by optogenetic silencing of the ipsCA1 projections onto conCA1. By contrast, in vivo fEPSP recordings reveal that ipsCA1-conCA1 synaptic efficacy is increased with delay over 24 h when generalization is formed but it is unchanged if generalization is disrupted. Direct excitation of ipsCA1-conCA1 synapses using chemogenetic hM3Dq facilitates generalization formation. Thus, rapid generalization is an active process dependent on bilateral CA1 regions, and encoded by gradual synaptic learning in ipsCA1-conCA1 circuit.

Figure 1. The ipsCA-conCA1 functional connectivity.

This study addressed here whether and how the hippocampal CA1 regions could process fear memory and generalization by recruiting separate mechanisms, and thereby minimizing interference of each another. In this study, the authors find a novel form of generalization with the characteristics of rapid development and easy extinction within 24 h after fear conditioning training. This rapid generalization but not fear memory is processed by the interhemispheric exchanges of the fear memory information allocated in bilateral CA1, leading to a gradual developing synaptic potentiation in the ipsCA1–conCA1 circuit within 24 h.
 
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