The viruses used in this article are in the table below

The lateral entorhinal cortex (LEC) receives direct input fromolfactory bulbmitral cells and piriformcortical pyramidal cells and is the gateway for olfactory input to the hippocampus. However, the LEC also projects back to the piriformcortex and olfactory bulb. Activity in the LEC is shaped by input from the perirhinal cortices, hippocampus, and amygdala, and thus could provide a rich contextual modulation of cortical odor processing. The present study further explored LEC feedback to anterior piriformcortex by examining how LEC top-down input modulates anterior piriform cortex odor evoked activity in rats. Retrograde viral tracing confirmed rich LEC projections to both the olfactory bulb and piriform cortices. In anesthetized rats, reversible lesions of the ipsilateral LEC increased anterior piriform cortical single-unit spontaneous activity. In awake animals performing an odor discrimination task, unilateral LEC reversible lesions enhanced ipsilateral piriformcortical local field potential oscillations during odor sampling, withminimal impact on contralateral activity. Bilateral LEC reversible lesions impaired discrimination performance on a well learned, difficult odor discrimination task, but had no impact on a well learned simple odor discrimination task. The simple discrimination task was impaired by bilateral reversible lesions of the anterior piriform cortex. Given the known function of LEC in working memory and multisensory integration, these results suggest itmay serve as a powerful top-downmodulator of olfactory cortical function and odor perception. Furthermore, the results provide potential insight into how neuropathology in the entorhinal cortex could contribute to early olfactory deficits seen in Alzheimer’s disease.

Figure 1. Retrogradely labeled neurons in LEC following viral injections into the olfactory bulb (GFP) or the aPCX (mCherry). Labeled neurons were distributed throughout the LEC, especially in layers II–V in the ipsilateral LEC, with the most robust labeling observed after aPCX infections. With these markers, no double-labeled cells were observed in any animal.

In this study, the authors explore the consequences of reversible LEC lesions on olfactory cortical activity and perception. The results suggest a robust modulation of both spontaneous and odor-evoked piriform cortical activity by the LEC, and a loss of fine odor discrimination ability during reversible LEC silencing.
 
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