Biology subjects

Clawson, B. C.

Publications and source records attributed to Clawson, B. C..

4 recordsLinked to original sources

bioRxiv2023

Hypnotic treatment reverses NREM sleep disruption and EEG desynchronization in a mouse model of Fragile X syndrome to rescue memory consolidation deficits.

Fragile X syndrome (FXS) is a highly-prevalent genetic cause of intellectual disability, associated with disrupted cognition and sleep abnormalities. Sleep loss itself negatively impacts cognitive function, yet the contribution of sleep loss to impaired cognition in FXS is vastly understudied. One untested possibility is that disrupted cognition in FXS is exacerbated by abnormal sleep. We hypothesized that restoration of sleep-dependent mechanisms could improve functions such as memory consolidation in FXS. We examined whether administration of ML297, a hypnotic drug acting on G-protein-activated inward-rectifying potassium channels, could restore sleep phenotypes and improve disrupted memory consolidation in Fmr1-/y mice. Using 24-h polysomnographic recordings, we found that Fmr1-/y mice exhibit reduced non-rapid eye movement (NREM) sleep and fragmented NREM sleep architecture, alterations in NREM EEG spectral power (including reductions in sleep spindles), and reduced EEG coherence between cortical areas. These alterations were reversed in the hours following ML297 administration. Hypnotic treatment following contextual fear or spatial learning also ameliorated disrupted memory consolidation in Fmr1-/y mice. Hippocampal activation patterns during memory recall was altered in Fmr1-/y mice, reflecting an altered balance of activity among principal neurons vs. parvalbumin-expressing (PV+) interneurons. This phenotype was partially reversed by post-learning ML297 administration. These studies suggest that sleep disruption could have a major impact on neurophysiological and behavioral phenotypes in FXS, and that hypnotic therapy may significantly improve disrupted cognition in this disorder.

neuroscience↗

bioRxiv2022

Binocular visual experience and sleep promote visual cortex plasticity and restore binocular vision in a mouse model of amblyopia

Amblyopia arises from an altered balance of input from the two eyes to the binocular zone of primary visual cortex (bV1) during childhood, causing long-lasting visual impairment. Amblyopia is commonly treated by patching the dominant eye, however, the relative impacts of monocular vs. binocular visual experiences on restoration of bV1 function remains unclear. Moreover, while sleep has been implicated in V1 plasticity in response to vision loss, its role in recovery from amblyopia is unknown. We used monocular deprivation (MD) in juvenile mice to model amblyopia in bV1. We compared recovery of visual responses for the two eyes among bV1 regular spiking (RS, putative principal) neurons and fast-spiking (FS, putative parvalbumin-expressing [PV+]) interneurons after identical-duration, identical-quality binocular recovery (BR) or monocular, reverse occlusion (RO) experiences. We find that BR is quantitatively superior to RO with respect to renormalizing both bV1 populations visual responses. However, this recovery was seen only in freely-sleeping mice; post-BR sleep deprivation prevented functional recovery. Thus, both binocular visual experience and subsequent sleep are required to optimally renormalize bV1 responses in a mouse model of amblyopia.

neuroscience↗

bioRxiv2021

Binocular vs. monocular recovery experience differentially promote recovery from visual deficits in a mouse model of amblyopia

Altered visual experience during monocular deprivation (MD) profoundly changes in ocular dominance (OD) in the developing primary visual cortex (V1). MD-driven changes in OD are an experimental model of amblyopia, where early-life alterations in vision lead visual disruption in adulthood. Current treatments for amblyopia include patching of the dominant eye, and more recently-developed binocular therapies. However, the relative impact of monocular vs. binocular recovery experiences on recovery of function in V1 is not well understood. Using single-unit recording, we compared how binocular recovery [BR] or reverse occlusion [RO] of identical duration and content affects OD and visual response recovery in mouse binocular V1 after a period of MD. We also tested how BR and RO affected MD-driven alterations of parvalbumin expression, and visually-driven expression of cFos in parvalbumin-positive and negative neurons. Finally, we tested how BR and RO affected recovery of normal visual acuity for the two eyes in the context of visually-driven behavior. We find that BR is quantitatively superior with respect to normalization of V1 neurons OD, visually-driven cFos expression, and visual acuity for the two eyes. However, MD-driven changes in the firing rate and response properties of V1 principal neuron and fast-spiking interneuron populations do not recover fully after either BR or RO. Binocular matching of orientation preference also remains disrupted in V1 neurons after both forms of recovery experience. Thus BR and RO, analogs of differing treatment regimens for amblyopia, differentially impact various aspects of visual recovery in a mouse model for amblyopia. Significance StatementAmblyopia resulting from altered childhood eye function is a leading cause of lifelong vision loss. Treatment typically involves patching of the dominant eye (forcing monocular visual experience), and produces only partial recovery of vision. Using a well-established mouse model of amblyopia, we directly compared how two types of visual experiences influence recovery of visual function. Our findings suggest that binocular vs. monocular visual experience differentially effect restoration of normal visual responses in cortical neurons, visually-driven neuronal gene expression, and visual acuity. Understanding how the quality of recovery experience impacts visual system recovery in amblyopia should provide critical insights for clinical strategies for its treatment.

neuroscience↗

bioRxiv2019

Network resonance during slow-wave sleep facilitates memory consolidation through phase-coding

Sleep plays a critical role in memory consolidation, however, the exact role that sleep and its effects on neural network dynamics play in this process is still unclear. Here, we combine computational and experimental approaches to study the dynamical, network-wide underpinnings of hippocampal memory consolidation during sleep. We provide data to support a novel hypothesis on the role of cellular resonance with sleep-associated theta band (4-12 Hz) hippocampal oscillations in this process. We show that increases in the stability of hippocampal memory representations after learning (which predicts successful memory consolidation) are mediated through emergent network-wide resonance and locking of neuronal activity to network oscillations. These changes arise in the network as a function of changes to network structure during learning, and mirror experimental findings in the hippocampus. Finally, we show that input-dependent pattern formation (e.g. "replay") in the hippocampus during sleep states, together with spike timing dependent plasticity (STDP)-based memory consolidation, leads to universal network activity reorganization. This reorganization generates heterogeneous changes in neuronal spiking frequency, similar to what has been observed in a variety of brain circuits across periods of sleep. Our results support the hypothesis that sleep plays an active role in memory consolidation by switching the hippocampal network from rate-based to phase-based information representation. The mechanisms through which this occurs supports the integration of heterogeneous cell populations into memory traces. Significance StatementIn this study, we provide a mechanistic explanation of how sleep selectively facilitates memory consolidation, through recruitment of heterogeneous neuronal populations and structural reorganization of the network into an engram. Specifically, we show that emergent theta band oscillations during sleep facilitate stabilization of memory representations via spike timing dependent reinforcement. This stabilization, together with STDP, allows for systematic reorganization of synaptic connections within these populations, universally redistributing firing rates of participating neurons. Simultaneously, network oscillations facilitate a switch from rate-to phase-coding of information among neuronal populations with highly heterogenous firing frequencies, incorporating more neurons into the engram. Our results reconcile discrepant findings on network reorganization during sleep, and demonstrate a clear mechanism for both strengthening and weakening of synaptic efficacy during sleep.

neuroscience↗