Lateral entorhinal cortex contribution to context-dependent odor processing in the piriform cortex

Sensory representations in the cortex are shaped not only by stimulus features but also by contextual and behavioral signals. In the piriform cortex (PC), neurons initially tuned to odors become modulated by non-olfactory variables such as visual context, but it remains unclear which associative inputs drive this modulation. A candidate source is the lateral entorhinal cortex (LEC), a region involved in context encoding and memory that is monosynaptically connected to PC. We hypothesize that LEC projections to PC provide contextual information and that their inhibition will alter both PC coding and behavioural performance. We developed a dual-virus system to express inhibitory DREADDs specifically in LEC projection neurons to PC. Unexpectedly, DREADD expression also appeared within PC itself, rather than being restricted to LEC, revealing extensive reciprocal connectivity between the two regions and suggesting that a subset of neurons within the recurrent PC circuitry projects back to LEC. In parallel, acute Neuropixels recordings were established with the goal of targeting multiple regions at once. We began with hippocampal recordings to optimize the approach, and used dummy-probes to confirm we can accurately reach both LEC and PC, enabling future simultaneous recordings. Ongoing experiments will assess how the pathway inhibition alters neural representations and task performance, and lays groundwork to test how contextual signals are integrated into olfactory circuits.