Cell-type-specific regulation of persistent activity in the lateral entorhinal cortex by hippocampal CA1 feedback

The lateral entorhinal cortex (LEC) serves as a critical gateway for integrating nonspatial sensory information into the hippocampal memory system, yet the cellular and circuit mechanisms underlying its auditory processing remain unclear. In this study, using in vivo loose-patch recordings, we systematically identified three distinct types of neurons in the LEC that differentially respond to white noise: transient-type neurons, predominantly located in the deep layers, and nontransient sustained-type and transient-sustained-type neurons, mainly residing in the superficial layers. These three types exhibited significant differences in firing patterns, response latency, and duration. Retrograde tracing confirmed that the LEC receives projections from multiple upstream regions, including the dorsal hippocampal CA1 (dCA1). Selective chemogenetic inhibition of the dCA1-to-LEC pathway significantly reduced the firing rate of LEC neurons. It shortened the response duration of both nontransient sustained-type and transient-sustained-type neurons, while leaving transient-type neurons unaffected. These results reveal that the hippocampal dCA1, via top-down feedback, selectively modulates the activity of LEC neurons exhibiting persistent firing, thereby endowing their auditory responses with temporal dynamics that may support memory encoding. Our study elucidates key features of auditory processing in the LEC and provides a novel mechanism for understanding the role of the hippocampal-entorhinal circuit in sensory information processing.NEW & NOTEWORTHY This study provides the first in vivo evidence that auditory-responsive neurons in the lateral entorhinal cortex (LEC) are organized into three functionally distinct types. We demonstrate that hippocampal CA1 feedback selectively sustains the prolonged firing of neurons with persistent activity profiles, revealing a cell-type-specific mechanism through which the hippocampus dynamically shapes temporal representations of sound in the entorhinal cortex.