Biology subjects

Citri, A.

Publications and source records attributed to Citri, A..

8 recordsLinked to original sources

bioRxiv2026

Claustral Input Consolidates Anterior Cingulate Cortical States for Selective Behavior

Efficient behavior depends on consolidating selective strategies that prioritize informative cues and suppress irrelevant signals. Previous studies have implicated the claustrum in coordinating cortical activity and large-scale brain states across behavioral contexts, yet its precise contribution to online behavioral control versus the consolidation of frontal control strategies remains unresolved. Here we combined large-scale Neuropixels recordings with targeted optogenetic perturbation of claustral neurons projecting to the anterior cingulate cortex in behaving mice. During adaptation to altered task context and constraints, frontal cortical activity reorganized into a coordinated control regime characterized by sharpened encoding of task-relevant cues, suppression of non-instructive signals, structured low-frequency dynamics, and rapid transitions between population-level neural states. Temporally misaligned claustral signaling disrupted this reorganization, selectively impairing the consolidation of efficient, cue-selective strategies across sessions without affecting trial-by-trial task execution. These findings identify a role for the claustrum in shaping frontal dynamics that consolidate adaptive control strategies.

neuroscience↗

bioRxiv2026

Context-dependent reorganization of behavioral strategy during transfer from home-cage to head-fixed performance

Complex behavioral tasks increasingly rely on autonomous training paradigms that enable high-throughput learning in naturalistic settings. Such approaches offer a scalable route for preparing animals for subsequent head-fixed recordings required for high-resolution neural measurements. However, how animals adapt their behavioral strategies across these distinct contexts remains poorly understood. Here, we examine how mice trained autonomously in a group-housed home-cage system reorganize their behavior when transitioned to a head-fixed version of the same delayed-response task. Although overall success rates were comparable across contexts, mice exhibited a striking shift in behavioral policy. Freely behaving home-cage performance was characterized by high engagement and premature responses, whereas head-fixed performance showed a progressive emergence of selective, cue-intensity-dependent responding accompanied by increased omission errors. This selective strategy was strongly associated with improved performance and sustained engagement under head-fixed conditions, reflecting a trade-off between sensitivity to low-intensity cues and suppression of premature actions. Importantly, selectivity did not arise immediately upon head fixation but developed gradually with experience across sessions, indicating learned adaptation rather than a spontaneous response to restraint. Our findings demonstrate that behavioral policy is not solely determined by task rules or sensory demands, but is strongly shaped by task architecture, temporal constraints, and opportunity cost. These results highlight the need to account for context-dependent strategy shifts when interpreting neural activity following transfer from autonomous training to controlled recording environments, and establish a framework for studying adaptive behavior across experimental contexts.

animal behavior and cognition↗

bioRxiv2025

The Quest for a Universal Parkinson's Transcriptomics Signature is Derailed by Inherent Variability between Patients

ObjectiveTo systematically evaluate the reproducibility and clinical utility of published blood mRNA-based gene signatures for classifying PD from healthy controls, and to uncover the pitfalls that limit their performances. MethodsWe validated the classification performance of 13 gene signatures unique for PD (published 2015-2025) using the Parkinsons Progression Markers Initiative (PPMI) database. We further validated classification performance on data collected in a prospective clinical trial where demographic and clinical parameters were minimized and environmental confounders were strictly controlled. Sources of gene expression variability were studied by mean pairwise distance analysis. ResultsGene overlap between signatures was low (11/411, 2.7%) but statistically significant (P<0.001) and enriched with genes involved in lipid metabolism. The majority (10/13) of these signatures retained statistical significance when tested on the PPMI dataset, but their classification performance was modest (median AUC 59.7%), substantially lower than originally reported. Classification performance improved when comparing GBA1-associated PD to controls (median AUC 65.4%, P=0.006). A prospective trial (16 PD patients, 14 controls) with rigorous environmental standardization did not improve classification accuracy. Inter-individual expression variability is the dominant limiting factor in classifier performance. Variability was not impacted by long-term levodopa therapy. InterpretationWhile blood transcriptomic signatures unique to PD are reproducible and may elucidate PD pathophysiology, their broad clinical utility remains severely limited by inherent inter-individual variability. Future research should prioritize biomarkers of divergence rather than the pursuit of a universal PD signature.

bioinformatics↗

bioRxiv2025

PyMouse Lifter: Real Time 3-D Pose Estimation for Mice with Only 2-D Annotation Via Data Synthesis

Neural-network-based pose estimation models have become increasingly popular for quantitative analysis of mouse behavior, yet most recordings still use a single 2-D camera view and therefore lack the depth cues needed for accurate 3-D kinematics. Existing open-source 3-D mouse datasets for training deep-learning models cover only a narrow range of environments and do not generalize well to various laboratory settings. To overcome these limitations, we introduce PyMouse Lifter, a pipeline that automatically reconstructs 3-D mouse poses from ordinary 2-D top-view videos with minimal manual 2-D annotation. PyMouse Lifter combines (i) an anatomically realistic 3-D mouse model for automated data synthesis, (ii) a monocular depth estimation model, and (iii) a 2-D key-point estimation model, enabling accurate 3-D reconstruction (model-based 3D inference) in virtually any open-field arena without using depth or multiple camera views for reconstruction. We validate the system on multiple datasets against depth-camera ground truth and show that the lifted 3D trajectories yield improved behavior classification over 2-D data and can be implemented in real time.

neuroscience↗

bioRxiv2023

Striatal calcium transients detected by fiber photometry propagate to axons

ARISING FROM: A. Legaria et al., Nature Neuroscience https://doi.org/10.1038/s41593-022-01152-z (2022). Calcium fiber photometry is a popular technique for recording the activity of neuronal populations defined by their gene expression or connectivity. In a recent study, Legaria et al., present evidence that the calcium signal recorded with fiber photometry primarily reports local fluctuations in neuropil Ca2+, rather than somatic Ca2+ influx corresponding to neural firing, as has been assumed by the field. This raises the question of whether fiber photometry transients are a valid measure of the propagation of information from neural soma to their axons. We addressed this question directly, recording coincident activity from both the somato-dendritic region and downstream axons of striatal neural populations. Our findings demonstrate that calcium events are reliably propagated to axons, supporting the interpretation that these events reflect neuronal firing.

neuroscience↗

bioRxiv2021

Claustral Projections to Anterior Cingulate Cortex Modulate Engagement with the External World

Engagement is a major determinant of performance. Hyper-engagement risks impulsivity and is fatiguing over time, while hypo-engagement could lead to missed opportunities. Even in sleep, when engagement levels are minimal, sensory responsiveness varies. Thus, maintaining an optimal engagement level with the environment is a fundamental cognitive ability. The claustrum, and in particular its reciprocal connectivity with executive regions in the frontal cortex, has been associated with salience, attention and sleep. These apparently disparate roles can be consolidated within the context of engagement. Here we describe the activity of claustro-frontal circuits in a task imposing a tradeoff between response inhibition and sensory acuity ( ENGAGE). Recording calcium fiber photometry during >80,000 trials, we characterize claustrum recruitment during salient behavioral events, and find that a moderate level of activity in claustro-cingulate projections defines optimal engagement. Low activity of this pathway is associated with impulsive actions, while high activity is associated with behavioral lapses. Chemogenetic activation of cingulate-projecting claustrum neurons suppressed impulsive behavior and reduced the engagement of mice in the task. This relationship became even clearer upon addressing individual variability in the strategy mice employed during the ENGAGE task. Furthermore, this association of claustrum activity and engagement extends into sleep. Using simultaneous EEG and photometry recordings in the claustrum, we find that cingulate projecting claustrum neurons are most active during deep unresponsive slow-wave sleep, when mice are less prone to awakening by sensory stimuli.

neuroscience↗

bioRxiv2020

Egr2 induction in Drd1+ ensembles of the ventrolateral striatum supports the development of cocaine reward

Drug addiction develops due to brain-wide plasticity within neuronal ensembles, mediated by dynamic gene expression. Though the most common approach to identify such ensembles relies on immediate early gene expression, little is known of how the activity of these genes is linked to modified behavior observed following repeated drug exposure. To address this gap, we present a broad-to-specific approach, beginning with a comprehensive investigation of brain-wide cocaine-driven gene expression, through the description of dynamic spatial patterns of gene induction in subregions of the striatum, and finally address functionality of region-specific gene induction in the development of cocaine preference. Our findings reveal differential cell-type specific dynamic transcriptional recruitment patterns within two subdomains of the dorsal striatum following repeated cocaine exposure. Furthermore, we demonstrate that induction of the IEG Egr2 in the ventrolateral striatum, as well as the cells within which it is expressed, are required for the development of cocaine seeking. Impact statementVLS ensembles are dynamically recruited by cocaine experiences to mediate cocaine reward.

neuroscience↗

bioRxiv2017

Salient Experiences are Represented by Unique Transcriptional Signatures in the Brain

Inducible transcription is essential for consolidation of salient experiences into long-term memory. However, the question of whether inducible transcription relays information representing the identity of the experience being encoded, has not been explored. To this end, we have analyzed transcription across multiple brain regions, induced by a variety of rewarding and aversive experiences. Our results define robust transcriptional signatures uniquely characterizing individual salient experiences. A subset of these induced transcriptional markers suffice for near-perfect decoding of the identity of recent experiences at the level of individual mice. Furthermore, experiences with shared attributes display commonalities in their transcriptional representation, exemplified in the representation of valence, habituation and reinforcement. Taken together, our results demonstrate the existence of a neural transcriptional code that represents the encoding of experiences in the mouse brain. This code is comprised of distinct transcriptional signatures that correlate to the affective attributes of the experiences that are being encoded.

neuroscience↗