Lateral entorhinal cortex afferents reconfigure the activity in piriform cortex circuits

Odors are key signals for guiding spatial behaviors such as foraging and navigation in rodents. Recent findings reveal that odor representations in the piriform cortex (PCx) also encode spatial context information. However, the brain origins of this information and its integration into PCx microcircuitry remain unclear. This study investigates the lateral entorhinal cortex (LEC) as a potential source of spatial contextual information affecting the PCx microcircuit and its olfactory responses. Using mice brain slices, we performed patch-clamp recordings on superficial (SP) and deep (DP) pyramidal neurons, as well as parvalbumin (PV) and somatostatin (SOM) inhibitory interneurons. Concurrently, we optogenetically stimulated excitatory LEC projections to observe their impact on PCx activity. Results show that LEC inputs are heterogeneously distributed in the PCx microcircuit, evoking larger excitatory currents in SP and PV neurons due to higher monosynaptic connectivity. LEC inputs also differentially affect inhibitory circuits, activating PV while suppressing SOM interneurons. Studying the interaction between LEC inputs and sensory signals from the lateral olfactory tract (LOT) revealed that simultaneous LEC and LOT activation increases spiking in SP and DP neurons, with DP neurons showing a sharpened response due to LEC-induced inhibition that suppresses delayed LOT-evoked spikes. This suggests a regulatory mechanism where LEC inputs inhibit recurrent activity by activating PV interneurons. Our findings demonstrate that LEC afferents reconfigure PCx activity, aiding the understanding of how odor objects form within the PCx by integrating olfactory and nonolfactory information.