Biology subjects

Kimchi, E. Y.

Publications and source records attributed to Kimchi, E. Y..

8 recordsLinked to original sources

bioRxiv2026

Camus: a video-based framework for continuous behavioral monitoring in the mouse home-cage

Home-cage activity is a window into the spontaneous behavioral repertoire of mice. These behaviors are organized across the circadian cycle, and disruptions in their duration, frequency, or organization may provide sensitive measures of neurological or psychiatric dysfunction. While continuous monitoring can help track the dynamics of spontaneous behavior, video recording in conventional laboratory cages is limited by compact cage geometry, opaque cage tops, and obstructed views of animals, food, and water. We therefore developed Camus, a Camera for home-cage recordings of Mus musculus mice. Camus integrates off-the-shelf USB cameras with infrared illumination and custom 3D-printed components for access to food and water without obstructed views. The modular design pairs continuous video acquisition with a manually validated computer-vision model to quantify locomotion, feeding, drinking, and nesting-related behavior across multiday recordings. A single desktop computer can record as many as 20 cages in parallel at an incremental cost of approximately $250 per cage, recording more than 99% of expected frames at 640x360-pixel resolution and 30 frames per second. Camus captured circadian structure in locomotion, feeding, and drinking. Camus also captured nest-building and sex-specific differences in nest dynamics. Using Camus with transgenic 5xFAD mice overexpressing amyloid revealed selective, age-progressive deficits in nesting behavior. Camus provides a scalable, open-source platform that combines accessible hardware, automated video monitoring, and machine-learning based analysis for continuous and potentially longitudinal behavioral phenotyping.

animal behavior and cognition↗

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↗

bioRxiv2025

Separable Dorsal Raphe Dopamine Projections mediate the Facets of Loneliness-like state

Affiliative social connections facilitate well-being and survival in numerous species. Engaging in social interactions requires positive or negative motivational drive, elicited through coordinated activity across neural circuits. However, the identity, interconnectivity, and functional encoding of social information within these circuits remains poorly understood. Here, we focus on downstream projections of dorsal raphe nucleus (DRN) dopamine neurons (DRNDAT), which we previously implicated in social motivation alongside an aversive affective state. We show that three prominent DRNDAT projections - to the bed nucleus of the stria terminalis (BNST), central amygdala (CeA), and posterior basolateral amygdala (BLP) - play separable roles in behavior, despite substantial collateralization. Photoactivation of the DRNDAT-CeA projection promoted social behavior and photostimulation of the DRNDAT-BNST projection promoted exploratory behavior, while the DRNDAT-BLP projection supported place avoidance, suggesting a negative affective state. Downstream regions showed diverse receptor expression, poising DRNDAT neurons to act through dopamine, neuropeptide, and glutamate transmission. Furthermore, we show ex vivo that the effect of DRNDAT photostimulation on downstream neuron excitability depended on region and baseline cell properties, resulting in excitatory responses in BNST cells and diverse responses in CeA and BLP. Finally, in vivo microendoscopic cellular-resolution recordings in the CeA with DRNDAT photostimulation revealed a correlation between social behavior and neurons excited by social stimuli- suggesting that increased dopamine tone may recruit different CeA neurons to social ensembles. Collectively, these circuit features may facilitate a coordinated, but flexible, response in the presence of social stimuli that can be flexibly guided based on the internal social homeostatic need state of the individual.

neuroscience↗

bioRxiv2023

Potentiated cholinergic and corticofugal inputs support reorganized sensory processing in the basolateral amygdala during auditory threat acquisition and retrieval

Reappraising neutral stimuli as environmental threats reflects rapid and discriminative changes in sensory processing within the basolateral amygdala (BLA). To understand how BLA inputs are also reorganized during discriminative threat learning, we performed multi-regional measurements of acetylcholine (ACh) release, single unit spiking, and functional coupling in the mouse BLA and higher-order auditory cortex (HO-AC). During threat memory recall, sounds paired with shock (CS+) elicited relatively higher firing rates in BLA units and optogenetically targeted corticoamygdalar (CAmy) units, though not in neighboring HO-AC units. Functional coupling was potentiated for descending CAmy projections prior to and during CS+ threat memory recall but ascending amygdalocortical coupling was unchanged. During threat acquisition, sound-evoked ACh release was selectively enhanced for the CS+ in BLA but not HO-AC. These findings suggest that phasic cholinergic inputs facilitate discriminative plasticity in the BLA during threat acquisition that is subsequently reinforced through potentiated auditory corticofugal inputs during memory recall.

neuroscience↗

bioRxiv2022

Thalamus sends information about arousal but not valence to the amygdala

RationaleThe basolateral amygdala (BLA) and medial geniculate nucleus of the thalamus (MGN) have both been shown to be necessary for the formation of associative learning. While the role that the BLA plays in this process has long been emphasized, the MGN has been less well-studied and surrounded by debate regarding whether the relay of sensory information is active or passive. ObjectivesWe seek to understand the role the MGN has within the thalamoamgydala circuit in the formation of associative learning. MethodsHere, we use optogenetics to dissect the MGN-BLA circuit and explore the specific subpopulations for evidence of learning and synthesis of information that could impact downstream BLA encoding. We employ various machine learning techniques to investigate function within neural subpopulations. We introduce a novel method to investigate tonic changes across trial-by-trial structure, which offers an alternative approach to traditional trial-averaging techniques. ResultsWe find that the MGN appears to encode arousal but not valence, unlike the BLA which encodes for both. We find that the MGN and the BLA appear to react differently to expected and unexpected outcomes; the BLA biased responses toward reward prediction error and the MGN focused on anticipated punishment. We uncover evidence of tonic changes by visualizing changes across trials during inter-trial intervals (baseline epochs) for a subset of cells. ConclusionWe conclude that the MGN-BLA projector population acts as both filter and transferer of information by relaying information about the salience of cues to the amygdala, but these signals are not valence-specified. PrefaceIn tribute to Nadia Chaudhri, and her discoveries regarding how contexts can modulate the representation of cues in the amygdala (Sciascia et al., 2015), and other mesolimbic circuit components (Chaudhri et al., 2009, 2008; Valyear et al., 2020), here we explore what information processing precedes entry into the basolateral amygdala (BLA) from the thalamus and develop visualization approaches for exploring across-trial temporal dynamics in addition to within-trial population activity.

neuroscience↗

bioRxiv2022

Reward contingency gates selective cholinergic suppression of amygdala neurons

Basal forebrain cholinergic neurons modulate how organisms process and respond to environmental stimuli through impacts on arousal, attention, and memory. It is unknown, however, whether basal forebrain cholinergic neurons are directly involved in conditioned behavior, independent of secondary roles in the processing of external stimuli. Using fluorescent imaging, we found that cholinergic neurons are active during behavioral responding for a reward - even in prior to reward delivery and in the absence of discrete stimuli. Photostimulation of basal forebrain cholinergic neurons, or their terminals in the basolateral amygdala (BLA), selectively promoted conditioned responding (licking), but not unconditioned behavior nor innate motor outputs. In vivo electrophysiological recordings during cholinergic photostimulation revealed reward-contingency-dependent suppression of BLA neural activity, but not prefrontal cortex (PFC). Finally, ex vivo experiments demonstrated that photostimulation of cholinergic terminals suppressed BLA projection neuron activity via monosynaptic muscarinic-receptor-signaling, while also facilitating firing in GABAergic interneurons. Taken together, we show that the neural and behavioral effects of basal forebrain cholinergic activation are modulated by reward contingency in a target-specific manner.

neuroscience↗

bioRxiv2018

Acute Food Deprivation Rapidly Modifies Valence-Coding Microcircuits in the Amygdala

In the quest for food, we may expend effort and increase our vulnerability to potential threats. Motivation to seek food is dynamic, varying with homeostatic need. What mechanisms underlie these changes? Basolateral amygdala neurons projecting to the nucleus accumbens (BLA[->]NAc) preferentially encode positive valence, whereas those targeting the centromedial amygdala (BLA[->]CeM) preferentially encode negative valence. Longitudinal in vivo two-photon calcium imaging revealed that BLA[->]NAc neurons were more active, while BLA[->]CeM neurons were less active, following just 1 day of food deprivation. Photostimulating BLA[->]CeM neurons inhibited BLA[->]NAc neurons at baseline, but food deprivation rapidly converted this inhibition into facilitation, supporting a model wherein BLA[->]NAc excitability mediates invigorated food-seeking behavior after deprivation. Indeed, inhibiting BLA[->]NAc reduced motivation for a caloric reinforcer in food deprived animals. Taken together, negative valence overrides positive valence processing in satiety, but changing homeostatic needs alter reward value via a rapid shift in the balance between projection-defined populations of BLA neurons.

neuroscience↗

bioRxiv2017

Acute stress induces long-lasting alterations in the dopaminergic system of female mice

Stress is a risk factor for many neuropsychiatric disorders, and the mesolimbic dopamine (DA) pathway is a crucial node of vulnerability. Despite the high prevalence of stress-related neuropsychiatric disorders in women, preclinical knowledge on the impact of stress on neural circuitry has predominantly been acquired in males. Here, we examine how a non-social stressor impacts the effect of DA neurotransmission on social and reward-related behaviors in female mice. Acute stress exposure attenuated the anti-social effects of photoinhibiting ventral tegmental area (VTA) DA neurons and transformed photoactivation of these cells into an anti-social signal. Fast-scan cyclic voltammetry (FSCV) revealed an enhancement in optogenetically-induced DA release after stress. 60 days after stress, mice showed distinct patterns of intra-cranial self-stimulation of VTA DA neurons. Our results reveal the impact stress exerts on females and show that neural and behavioral changes induced by acute stress exposure are still present months later.

neuroscience↗