Lateral entorhinal cortex afferents reconfigure the activity in piriform cortex circuits
Authors: Pedroncini Olivia , Federman Noel , Marin-Burgin Antonia 
Published: June 2024

AbstractOdours are key signals for guiding spatial behaviours such as foraging and navigation in rodents. It has recently been found that odour representations in the piriform cortex (PCx) can also contain information about their spatial context. However, the precise origins of this information within the brain and its subsequent integration into the microcircuitry of the PCx remains unknown. In this study, we focus on the lateral entorhinal cortex (LEC) as a candidate for carrying spatial contextual information to the PCx, to investigate how it affects the PCx microcircuit and its response to olfactory inputs. Utilising mice brain slices, we performed patch clamp recordings targeting both 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 study their impact on PCx activity. We found that LEC inputs are heterogeneously distributed in the PCx microcircuit, evoking larger excitatory currents in SP and PV neurons compared to DP and SOM neurons, respectively, due to their higher monosynaptic connectivity. Moreover, LEC inputs exert a differential effect on the inhibitory circuits, activating PV while suppressing SOM interneurons. We further studied the interaction among LEC inputs and the sensory afferent signals originating from the lateral olfactory tract (LOT) onto the PCx. Our findings demonstrated that both SP and DP neurons show a general increase in their spiking response when LEC and LOT are simultaneously activated. Notably, DP neurons exhibit a sharpening of their response attributable to LEC-induced inhibition that effectively suppresses the delayed spikes evoked by LOT stimulation. These observations suggest a regulatory mechanism whereby LEC inputs inhibit recurrent activity by activating PV interneurons. Our results show that LEC afferents reconfigure PCx activity and contribute to the understanding of how odour objects are formed within the PCx integrating both olfactory and contextual information.Significant statementPrimary sensory cortices are more complex than initially thought, encoding movement-related information, as well as spatial maps of animal location. The primary olfactory cortex, the piriform cortex (PCx), not only responds to the presence of odours, but to other non-olfactory signals like the spatial context in which odours are presented. The source of the contextual modulation is not known. In this work, we studied the modulation of PCx neurons by afferents arriving from the lateral entorhinal cortex (LEC), an area related to spatial representation. By the use of optogenetic to activate LEC inputs we found that its activation recruits excitatory and inhibitory circuits in PCx. The interaction of LEC inputs with afferents carrying odour information arriving from the lateral olfactory tract (LOT) resulted in a sharpening PCx principal neurons response to LOT, by a reduction in recurrent activity through PV interneurons. This circuital reorganisation of activity in PCx by LEC afferents could be an important mechanism to switch responses to be favouring dominance of the LOT pathway over the recurrent pathway. These results shed light on the understanding of how contextual aspects of animal experience, in which LEC is involved, can influence odour processing potentially leading to a richer representation of odour objects.