A longitudinal CA2/3 to CA1 circuit for initiating context-dependent associative learning

Associating environmental context with emotional experience is a vital brain function that requires the activity in both dorsal and ventral hippocampus. While only ventral hippocampus connects with the amygdala, a hub for fear learning, it remains unclear how the two hippocampal areas interact during contextual fear conditioning (CFC). We found that projections from dorsal CA2/CA3 (dCA2/3) to the dorsal part of ventral CA1 (vCA1d) contributed significantly to CFC. Deep-brain Ca2+ imaging revealed a CFC-enhanced difference in neuronal activities evoked by conditioned vs. neutral environmental context in both dCA2/3 and vCA1d areas. Notably, contextual fear retrieval correlated with changes in conditioned context-evoked activity in vCA1d, but not in dCA2/3. Furthermore, slice recordings showed that CFC potentiated dCA2/3-to-vCA1d projection strength, in line with coordinated elevation of monosynaptic excitation and reduction of disynaptic inhibition mediated by somatostatin-expressing interneurons. Thus, vCA1d represents a critical site for initiating emotional association with contextual information from dCA2/3.