The resonance properties of individual neurons in entorhinal cortex may contribute to their functional properties in awake, behaving rats. Models propose that entorhinal grid cells could arise from shifts in the intrinsic frequency of neurons caused by changes in membrane potential due to depolarizing input from neurons coding velocity. To test for potential changes in intrinsic frequency we measured the resonance properties of neurons at different membrane potentials in neurons in medial and lateral entorhinal cortex. In medial entorhinal neurons the resonant frequency of individual neurons decreased in a linear manner as the membrane potential was depolarized between −70 and −55 mV. At more hyperpolarized membrane potentials, cells asymptotically approached a maximum resonance frequency. Consistent with previous studies, near resting potential the cells of the medial EC possessed a decreasing gradient of resonance frequency along the dorsal to ventral axis, and cells of the lateral EC lacked resonant properties regardless of membrane potential or position along the medial to lateral axis within lateral EC. Application of 10 µM ZD7288, the H-channel blocker, abolished all resonant properties in MEC cells, and resulted in physiological properties very similar to lateral EC cells. These results on resonant properties show a clear change in frequency response with depolarization that could contribute to generation of grid cell firing properties in the medial entorhinal cortex.

Cortical representations underlying a wide range of cognitive abilities, which employ both rate and spike timing-based coding, emerge from underlying cortical circuits with a tremendous diversity of cell types. However, cell-type specific contributions to cortical coding are not well-understood. Here, we investigate the role of parvalbumin (PV) neurons in cortical complex scene analysis. Many complex scenes contain sensory stimuli, e.g., natural sounds, images, odors or vibrations, which are highly dynamic in time, competing with stimuli at other locations in space. PV neurons are thought to play a fundamental role in sculpting cortical temporal dynamics; yet their specific role in encoding complex scenes via timing-based codes, and the robustness of such temporal representations to spatial competition, have not been investigated. Here, we address these questions in auditory cortex using a cocktail party-like paradigm; integrating electrophysiology, optogenetic manipulations, and a family of novel spike-distance metrics, to dissect the contributions of PV neurons towards rate and timing-based coding. We find that PV neurons improve cortical discrimination of dynamic naturalistic sounds in a cocktail party-like setting by enhancing rapid temporal modulations in rate and spike timing reproducibility. Moreover, this temporal representation is maintained in the face of competing stimuli at other spatial locations, providing a robust code for complex scene analysis. These findings provide novel insights into the specific contributions of PV neurons in cortical coding of complex scenes.

Much of our understanding about how acetylcholine modulates prefrontal cortical (PFC) networks comes from behavioral experiments that examine cortical dynamics during highly attentive states. However, much less is known about how PFC is recruited during passive sensory processing and how acetylcholine may regulate connectivity between cortical areas outside of task performance. To investigate the involvement of PFC and cholinergic neuromodulation in passive auditory processing, we performed simultaneous recordings in the auditory cortex (AC) and PFC in awake head fixed mice presented with a white noise auditory stimulus in the presence or absence of local cholinergic antagonists in AC. We found that a subset of PFC neurons were strongly driven by auditory stimuli even when the stimulus had no associative meaning, suggesting PFC monitors stimuli under passive conditions. We also found that cholinergic signaling in AC shapes the strength of auditory driven responses in PFC, by modulating the intra-cortical sensory response through muscarinic interactions in AC. Taken together, these findings provide novel evidence that cholinergic mechanisms have a continuous role in cortical gating through muscarinic receptors during passive processing and expand traditional views of prefrontal cortical function and the contributions of cholinergic modulation in cortical communication.

Cortical representations supporting many cognitive abilities emerge from underlying circuits comprised of several different cell types. However, cell type-specific contributions to rate and timing-based cortical coding are not well-understood. Here, we investigated the role of parvalbumin neurons in cortical complex scene analysis. Many complex scenes contain sensory stimuli which are highly dynamic in time and compete with stimuli at other spatial locations. Parvalbumin neurons play a fundamental role in balancing excitation and inhibition in cortex and sculpting cortical temporal dynamics; yet their specific role in encoding complex scenes via timing-based coding, and the robustness of temporal representations to spatial competition, has not been investigated. Here, we address these questions in auditory cortex of mice using a cocktail party-like paradigm, integrating electrophysiology, optogenetic manipulations, and a family of spike-distance metrics, to dissect parvalbumin neurons’ contributions towards rate and timing-based coding. We find that suppressing parvalbumin neurons degrades cortical discrimination of dynamic sounds in a cocktail party-like setting via changes in rapid temporal modulations in rate and spike timing, and over a wide range of time-scales. Our findings suggest that parvalbumin neurons play a critical role in enhancing cortical temporal coding and reducing cortical noise, thereby improving representations of dynamic stimuli in complex scenes.

Much of our understanding about how acetylcholine modulates prefrontal cortical (PFC) networks comes from behavioral experiments that examine cortical dynamics during highly attentive states. However, much less is known about how PFC is recruited during passive sensory processing and how acetylcholine may regulate connectivity between cortical areas outside of task performance. To investigate the involvement of PFC and cholinergic neuromodulation in passive auditory processing, we performed simultaneous recordings in the auditory cortex (AC) and PFC in awake head fixed mice presented with a white noise auditory stimulus in the presence or absence of local cholinergic antagonists in AC. We found that a subset of PFC neurons were strongly driven by auditory stimuli even when the stimulus had no associative meaning, suggesting PFC monitors stimuli under passive conditions. We also found that cholinergic signaling in AC shapes the strength of auditory driven response in PFC, by modulating the intra-cortical sensory response through muscarinic interactions in AC. Taken together, these findings provide novel evidence that cholinergic mechanisms have a continuous role in cortical gating through muscarinic receptors during passive processing and expand traditional views of prefrontal cortical function and the contributions of cholinergic modulation in sensory gating.HighlightsPrefrontal cortex actively monitors non-associative stimuli under passive conditionsAcetylcholine facilitates cortical signaling even outside of attentional contextsLocal scopolamine infusion reduced intracortical signaling and impaired cortical gatingmAChR have an ongoing role in sound processing

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