The role of the lateral entorhinal cortex in olfactory information processing

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Olfactory cues provide rich information about the local environment, critical for a diverse range of behaviors, such as food seeking, social interactions and predator avoidance. In mammals, olfactory information is initially processed in the olfactory bulb (OB) and subsequently encoded in primary olfactory (piriform) cortex (PCx). In contrast to detailed knowledge of olfactory information processing in OB and PCx, much less is known about higher areas, the lateral entorhinal cortex (LEC) and hippocampus, that are thought to directly regulate behaviors relying on odor memory and odor-guided navigation. In this project, I will use multi-site electrophysiological recordings and cell-type specific optogenetic manipulations to determine how olfactory information is processed across the entorhinal-hippocampal network in awake mice.The LEC receives two sources of olfactory input: direct projections from OB mitral cells and indirect projections via PCx. These inputs contact two subtypes of LEC principal cells in layer 2: “fan” cells which send direct projections to the dentate gyrus (DG) and pyramidal cells that project to the CA1 region of hippocampus. Odor-guided navigation relies on the ability to discriminate changes in odor intensity. OB responses are concentration-dependent, however, PCx responses have recently been shown to be largely invariant to odor concentration. I hypothesize that direct OB-LEC projections are critical for the processing of odor intensity coding in the entorhinal-hippocampal network.In preliminary experiments I established a preparation to achieve lateral access to the LEC in awake, behaving mice, allowing to investigate olfactory processing across layers. Simultaneous electrophysiological recordings from OB, LEC, DG and CA1 or OB, PCx and LEC with high-density extracellular probes will allow to investigate olfactory processing across areas at high temporal resolution. Electrophysiological recordings will be complemented with cell-type specific optogenetic tagging and manipulations to identify and perturb distinct components of the circuit during odor-guided behavior. To accomplish this, I have identified cre driver mice to specifically target LEC layer 2 fan and pyramidal cells. Ultimately, this project will establish mechanisms by which odor identity and intensity are processed and encoded in the LEC and hippocampus. Optogenetic perturbations of key pathways in the entorhinal-hippocampal network during odor-guided tasks will reveal their importance for different aspects of behavior. Elucidating the nature of olfactory processing in the entorhinal-hippocampal network will lead to a better understanding of pathways governing declarative memory and sensory-guided navigation. In addition to olfactory processing, the project provides new insight into LEC microcircuits, as well as entorhinal-hippocampal interactions.