During non-rapid eye-movement (NREM) sleep, cortical and thalamic neurons oscillate every second or so between ON periods, characterized by membrane depolarization and wake-like tonic firing, and OFF periods, characterized by membrane hyperpolarization and neuronal silence. Cortical slow waves, the hallmark of NREM sleep, reflect near-synchronous OFF periods in cortical neurons. However, the mechanisms triggering such OFF periods are unclear, as there is little evidence for somatic inhibition. We studied cortical inhibitory interneurons that express somatostatin (SOM), because ∼70% of them are Martinotti cells that target diffusely layer I and can block excitatory transmission presynaptically, at glutamatergic terminals, and postsynaptically, at apical dendrites, without inhibiting the soma. In freely moving male mice, we show that SOM+ cells can fire immediately before slow waves and their optogenetic stimulation during ON periods of NREM sleep triggers long OFF periods. Next, we show that chemogenetic activation of SOM+ cells increases slow-wave activity (SWA), slope of individual slow waves, and NREM sleep duration; whereas their chemogenetic inhibition decreases SWA and slow-wave incidence without changing time spent in NREM sleep. By contrast, activation of parvalbumin+ (PV+) cells, the most numerous population of cortical inhibitory neurons, greatly decreases SWA and cortical firing, triggers short OFF periods in NREM sleep, and increases NREM sleep duration. Thus SOM+ cells, but not PV+ cells, are involved in the generation of sleep slow waves. Whether Martinotti cells are solely responsible for this effect, or are complemented by other classes of inhibitory neurons, remains to be investigated. Cortical slow waves are a defining feature of non-rapid eye-movement (NREM) sleep and are thought to be important for many of its restorative benefits. Yet, the mechanism by which cortical neurons abruptly and synchronously cease firing, the neuronal basis of the slow wave, remains unknown. Using chemogenetic and optogenetic approaches, we provide the first evidence that links a specific class of inhibitory interneurons-somatostatin-positive cells-to the generation of slow waves during NREM sleep in freely moving mice.
SUMMARYCortical slow waves – the hallmark of NREM sleep - reflect near-synchronous OFF periods in cortical neurons. However, the mechanisms triggering such OFF periods are unclear, as there is little evidence for somatic inhibition. We studied cortical inhibitory interneurons that express somatostatin (SOM), because ∼70% of them are Martinotti cells that target diffusely layer 1 and can block excitatory transmission presynaptically, at glutamatergic terminals, and postsynaptically, at apical dendrites, without inhibiting the soma. In freely moving mice, we show that SOM+ cells can fire immediately before slow waves and their optogenetic stimulation triggers neuronal OFF periods during sleep. Next, we show that chemogenetic activation of SOM+ cells increases slow wave activity (SWA), the slope of individual slow waves, and the duration of NREM sleep; whereas their chemogenetic inhibition decreases SWA and slow wave incidence without changing time spent asleep. By contrast, activation of parvalbumin+ (PV+) cells, the most numerous population of cortical inhibitory neurons, greatly decreases SWA and cortical firing. These results indicate that SOM+ cells, but not PV+ cells, are involved in the generation of sleep slow waves. Whether Martinotti cells are solely responsible for this effect, or are complemented by other classes of inhibitory neurons, remains to be investigated.
Highlights d Dark stimuli in the central visual field drive strong OFF responses in awake mice d Dark and bright stimuli in the periphery drive more balanced OFF and ON responses d LFP and membrane potential responses in binocular V1 show clear OFF dominance d ON/OFF responses in V1 and lateral geniculate (LGN) show retinotopic alignment
SummaryRhythmic oscillations of neural activity permeate sensory systems. Studies in the visual system propose that broadband gamma oscillations (30 – 80 Hz) facilitate neuronal communication underlying visual perception. However, broadband gamma oscillations within and across visual areas show widely varying frequency and phase, providing constraints for synchronizing spike timing. Here, we analyzed data from the Allen Brain Observatory and performed new experiments that show narrowband gamma (NBG) oscillations (50 – 70 Hz) propagate and synchronize throughout the awake mouse thalamocortical visual system. Lateral geniculate (LGN) neurons fired with millisecond precision relative to NBG phase in primary visual cortex (V1) and multiple higher visual areas (HVAs). NBG in HVAs depended upon retinotopically aligned V1 activity, and neurons that fired at NBG frequencies showed enhanced functional connectivity within and across visual areas. Remarkably, LGN ON versus OFF neurons showed distinct and reliable spike timing relative to NBG oscillation phase across LGN, V1, and HVAs. Taken together, NBG oscillations may serve as a novel substrate for precise coordination of spike timing in functionally distinct subnetworks of neurons spanning multiple brain areas during awake vision.
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