Biology subjects

Chambers, A. R.

Publications and source records attributed to Chambers, A. R..

5 recordsLinked to original sources

bioRxiv2026

Spontaneous and stimulus-driven arousal produce distinct acetylcholine dynamics across sensory and prefrontal cortex

Acetylcholine (ACh) release from the basal forebrain has traditionally been viewed as a slow, spatially diffuse signal regulating cortical arousal across sleep and wakefulness1-3. Recent characterizations with higher resolution optical sensors have revealed rapid, local cholinergic modulation supporting dynamic changes in sensory processing, associative learning, and behavioral state4-7. However, sensory events that recruit cortical ACh often also change arousal and evoke movements, making it difficult to determine whether ACh transients reflect sensory features of environmental stimuli or the behavioral state changes that accompany sensory stimulation. To separate these contributions, we performed optic fiber recordings of a genetically encoded ACh fluorescent sensor in the auditory, visual, and prefrontal cortex of awake, head-fixed mice while monitoring pupil size and facial movements. Across cortical areas, ACh release tracked spontaneous fluctuations in arousal state, as indexed by pupil dilation and orofacial movements. Sensory stimuli also evoked rapid ACh transients, with sounds producing larger and more widespread responses than visual stimuli. Because sounds also elicited time-locked pupil dilations and facial movements, we used multivariate modeling to estimate the relative contributions of stimulus features, arousal, and behavior to cortical ACh dynamics. We identified a regional dissociation: sound-evoked ACh release in prefrontal cortex was largely explained by arousal- and movement-related variables, whereas auditory cortical ACh release retained a stronger relationship to stimulus features. These findings show that cortical ACh signaling reflects both shared arousal state and area-specific sensory processing and demonstrate that sound is especially effective at recruiting rapid, widespread cholinergic modulation across cortex.

neuroscience↗

bioRxiv2023

Mind the gap: A systematic review and meta-analysisof how social memory is studied

Social recognition is crucial for survival in social species, and necessary for group living, selective reproduction, pair bonding, and dominance hierarchies. Mice and rats are the most commonly used animal models in social memory research, however current paradigms do not account for the complex social dynamics they exhibit in the wild. To assess the range of social memories being studied, we conducted a systematic analysis of neuroscience articles testing the social memory of mice and rats published within the past two decades and analyzed their methods. Our results show that despite these rodents rich social memory capabilities, the majority of social recognition papers explore short-term memories and short-term familiarity levels with minimal exposure between subject and familiar stimuli - a narrow type of social memory. We have identified several key areas currently understudied or underrepresented: kin relationships, mates, social ranks, sex variabilities, and the effects of aging. Additionally, reporting on social stimulus variables such as housing history, strain, and age, is limited, which may impede reproducibility. Overall, our data highlight large gaps in the diversity of social memories studied and the effects social variables have on social memory mechanisms.

neuroscience↗

bioRxiv2023

Sound elicits stereotyped facial movements that provide a sensitive index of hearing abilities

Sound elicits rapid movements of muscles in the face, ears, and eyes that protect the body from injury and trigger brain-wide internal state changes. Here, we performed quantitative facial videography from mice resting atop a piezoelectric force plate and observed that broadband sounds elicit rapid, small, and highly stereotyped movements of a facial region near the vibrissae array. Facial motion energy (FME) analysis revealed sensitivity to far lower sound levels than the acoustic startle reflex and greater reliability across trials and mice than sound-evoked pupil dilations or movement of other facial and body regions. FME tracked the low-frequency envelope of sounds and could even decode speech phonemes in varying levels of background noise with high accuracy. FME growth slopes were disproportionately steep in mice with autism risk gene mutations and noise-induced sensorineural hearing loss, providing an objective behavioral measure of sensory hyper-responsivity. Increased FME after noise-induced cochlear injury was closely associated with the emergence of excess gain in later waves of the auditory brainstem response, suggesting a midbrain contribution. Deep layer auditory cortex units were entrained to spontaneous facial movements but optogenetic suppression of cortical activity facilitated - not suppressed - sound-evoked FME, suggesting the auditory cortex is a modulator rather than a mediator of sound-evoked facial movements. These findings highlight a simple involuntary behavior that is more sensitive and integrative than other auditory reflex pathways and captures higher-order changes in sound processing from mice with inherited and acquired hearing disorders.

neuroscience↗

bioRxiv2021

Cell-type-specific silence in thalamocortical circuits precedes hippocampal sharp-wave ripples.

Memory consolidation requires the encoding of neocortical memory traces, which is thought to occur during hippocampal oscillations called sharp-wave ripples (SWR). Evidence suggests that the hippocampus communicates memory-related neural patterns across distributed cortical circuits via its major output pathways. Here, we sought to understand how this information is processed in the retrosplenial cortex (RSC), a primary target circuit. Using patch-clamp recordings from mice during quiet wakefulness, we found that SWR-aligned synaptic modulation is widespread but weak, and that spiking responses are sparse. However, using cell type and projection-specific two-photon calcium imaging and optogenetics, we show that, starting 1-2 seconds before SWR, superficial inhibition in RSC is reduced, along with thalamocortical input. We propose that pyramidal dendrites experience a period of decreased local inhibition and subcortical interference in a seconds-long time window preceding hippocampal SWR. This may aid communication of weak and sparse SWR-aligned excitation between the hippocampus and neocortex, and promote the selective strengthening of memory-related connections.

neuroscience↗

bioRxiv2020

RippleNet: A Recurrent Neural Network for Sharp Wave Ripple (SPW-R) Detection

Hippocampal sharp wave ripples (SPW-R) have been identified as key bio-markers of important brain functions such as memory consolidation and decision making. SPW-R detection typically relies on hand-crafted feature extraction, and laborious manual curation is often required. In this multidisciplinary study, we propose a novel, self-improving artificial intelligence (AI) method in the form of deep Recurrent Neural Networks (RNN) with Long Short-Term memory (LSTM) layers that can learn features of SPW-R events from raw, labeled input data. The algorithm is trained using supervised learning on hand-curated data sets with SPW-R events. The input to the algorithm is the local field potential (LFP), the low-frequency part of extracellularly recorded electric potentials from the CA1 region of the hippocampus. The output prediction can be interpreted as the time-varying probability of SPW-R events for the duration of the input. A simple thresholding applied to the output probabilities is found to identify times of events with high precision. The reference implementation of the algorithm, named RippleNet, is open source, freely available, and implemented using a common open-source framework for neural networks (tensorflow.keras) and can be easily incorporated into existing data analysis workflows for processing experimental data.

neuroscience↗