SIGNIFICANCE STATEMENT Much is known about molecular mechanisms that facilitate sleep control. However, it is unclear how these pathways modulate neural circuit-level sensory processing or how misregulation of neural activity contributes to sleep disorders. The nematode Caenorhabditis elegans provides the ability to study neural circuitry with single-neuron resolution, and recent studies examined sleep states between developmental stages and when stressed. Here, we examine an additional form of spontaneous sleep in adult C. elegans at the behavioral and neural activity levels. Using a closed-loop system, we show that delayed behavioral responses to aversive chemical stimulation during sleep arise from sleep-dependent sensorimotor modulation localized presynaptic to the premotor circuit, rather than early sensory circuits.A central goal of neuroscience research is to understand how experiences modify brain circuits to guide future adaptive behavior. In response to environmental stimuli, neural circuit activity engages gene regulatory mechanisms within each cell. This activity-dependent gene expression is governed, in part, by epigenetic processes that can produce persistent changes in both neural circuits and the epigenome itself. The complex interplay between circuit activity and neuronal gene regulation is vital to learning and memory, and, when disrupted, is linked to debilitating psychiatric conditions, such as substance use disorder. INS018055 To develop clinical treatments, it is paramount to advance our understanding of how neural circuits and the epigenome cooperate to produce behavioral adaptation. Here, we discuss how new genetic tools, used to manipulate neural circuits and chromatin, have enabled the discovery of epigenetic processes that bring about long-lasting changes in behavior relevant to mental health and disease.The ventromedial (VM)/ventro-anterior-lateral (VAL) motor thalamus is a key junction within the brain circuits sustaining normal and pathologic motor control functions and decision-making. In this area of thalamus, on one hand, the inhibitory nigro-thalamic pathway provides a main output from the basal ganglia, and, on the other hand, motor thalamo-cortical loops are involved in the maintenance of ramping preparatory activity before goal-directed movements. To better understand the nigral impact on thalamic activity, we recorded electrophysiological responses from VM/VAL neurons while male and female mice were performing a delayed right/left decision licking task. Analysis of correct (corr) and error trials revealed that thalamic ramping activity was stronger for premature licks (impulsive action) and weaker for trials with no licks [omission (omi)] compared with correct trials. Suppressing ramping activity through optogenetic activation of nigral terminals in the motor thalamus during the delay epoch of the ol this ramping activity and determine the timing of action initiation.Proper perception of sounds in the environment requires auditory signals to be encoded with extraordinary temporal precision up to tens of microseconds, but how it originates from the hearing organs in the periphery is poorly understood. In particular, sound-evoked spikes in auditory afferent fibers in vivo are phase-locked to sound frequencies up to 5 kHz, but it is not clear how hair cells can handle intracellular Ca2+ changes with such high speed and efficiency. In this study, we combined patch-clamp recording and two-photon Ca2+ imaging to examine Ca2+ dynamics in hair cell ribbon synapses in the bullfrog amphibian papilla of both sexes. We found that Ca2+ clearance from single synaptic ribbons followed a double exponential function, and the weight of the fast component, but not the two time constants, was significantly reduced for prolonged stimulation, and during inhibition of the plasma membrane Ca2+ ATPase (PMCA), the mitochondrial Ca2+ uptake (MCU), or the sarcolemma/endoplasmic reticulum Ca2+ ATPaseernal Ca2+ and at physiological temperature. By stimulating hair cells with sinusoidal voltage commands that mimic pure sound tones, we recapitulated the phase-locking of hair cell exocytosis with an in vitro approach. This allowed us to reveal the Ca2+ extrusion mechanisms that are required for phase-locking at auditory hair cell ribbon synapses.Cognitive deficits following traumatic brain injury (TBI) remain a major cause of disability and early-onset dementia, and there is increasing evidence that chronic neuroinflammation occurring after TBI plays an important role in this process. However, little is known about the molecular mechanisms responsible for triggering and maintaining chronic inflammation after TBI. Here, we identify complement, and specifically complement-mediated microglial phagocytosis of synapses, as a pathophysiological link between acute insult and a chronic neurodegenerative response that is associated with cognitive decline. Three months after an initial insult, there is ongoing complement activation in the injured brain of male C57BL/6 mice, which drives a robust chronic neuroinflammatory response extending to both hemispheres. This chronic neuroinflammatory response promotes synaptic degeneration and predicts progressive cognitive decline. Synaptic degeneration was driven by microglial phagocytosis of complement-opsonized synarther that this response is associated with cognitive decline. Complement inhibition interrupted this response and reversed cognitive decline, even when therapy was delayed until 2 months after injury. The data further support the concept that TBI should be considered a chronic rather than an acute disease condition, and have implications for the management of TBI in the chronic phase of injury, specifically with regard to the therapeutic application of complement inhibition.Object recognition tasks are widely used assays for studying learning and memory in rodents. Object recognition typically involves familiarizing mice with a set of objects and then presenting a novel object or displacing an object to a novel location or context. Learning and memory are inferred by a relative increase in time investigating the novel/displaced object. These tasks are in widespread use, but there are many inconsistencies in the way they are conducted across labs. Two major contributors to this are the lack of consistency in the method of measuring object investigation and the lack of standardization of the objects that are used. Current video-based automated algorithms can often be unreliable whereas manual scoring of object investigation is time consuming, tedious, and more subjective. To resolve these issues, we sought to design and implement 3D-printed objects that can be standardized across labs and use capacitive sensing to measure object investigation. Using a 3D printer, conductive filament, and low-cost off-the-shelf components, we demonstrate that employing 3D-printed capacitive touch objects is a reliable and precise way to perform object recognition tasks.