Biology subjects

Groysman, M.

Publications and source records attributed to Groysman, M..

9 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↗

bioRxiv2025

Astrocytic Activation Completely Corrects Memory Performancein an Alzheimer's Disease Model

Neural and glial dysfunction are thought to underlie memory impairments in Alzheimers disease (AD). Conversely, astrocytes are known to play a central role in the healthy brain, and their activation has been shown to enhance memory. To test whether activation of astrocytes can correct memory deficits associated with AD, we expressed hM3Dq in CA1 astrocytes of 7 months old 5XFAD AD model mice, enabling astrocytic chemogenetic Gq pathway activation, following exposure to CNO. We report that astrocytic activation results in complete memory correction, and even memory improvement of AD model mice beyond that of untreated WT levels. We went further to discover the mechanisms underlying this memory improvement in AD mice: First, using 2-photon imaging and electrophysiology, we observed increased neuronal activity (displayed as elevated cFos expression and amplified awake Ca2+ events) as well as augmented in-vivo long term plasticity following astrocytic activation. Subsequently, we observed increased astrocytic endocytosis of A{beta} plaques. Finally, we report that the beneficial effects of astrocytic activation remained stable for an entire year, and persisted beyond the window of astrocytic Gq activation. Our findings that astrocytes correct memory impairments in an AD model could have important clinical implications towards treating this disease.

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.

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bioRxiv2023

Astrocytes Control Recent and Remote Memory Strength by Affecting the Recruitment of the CA1->ACC Projection to Engrams

Recent and remote memories are encoded throughout the brain in Engrams: cell ensembles formed during acquisition, and upon their reactivation, a specific memory can be recalled. The maturation of engrams from recent to remote time points involves the recruitment of CA1 neurons projecting to the anterior cingulate cortex (CA1[->]ACC). Various modifications to CA1 astrocytes, to the Gq- or Gi-GPCR pathways, during memory acquisition were shown to affect recent and remote recall in seemingly contradictory ways. To address the inconsistency, we applied transgenic approaches for ensemble identification, CLARITY, retro-AAV virus for circuit mapping, and chemogenetics in astrocytes for functional investigation. We manipulated the activity of either Gq- or Gi-pathways in CA1 astrocytes during memory acquisition and tagged cFos+ engram cells and CA1[->]ACC cells during recent and remote recall in the same animals. The behavioral results were coupled with changes in the recruitment of CA1[->]ACC projection cells to the engram, demonstrated by the number of CA1[->]ACC projecting cells in the engram as well as the number of axons projecting from the CA1 engram toward the ACC: Gq pathway activation in astrocytes caused enhancement of recent recall alone and was accompanied by earlier recruitment of CA1[->]ACC projecting cells to the engram. In contrast, when activating the Gi pathway in astrocytes during acquisition, only remote recall was impaired, and CA1[->]ACC projecting cells were not recruited during remote memory. Finally, we provide a simple working model, hypothesizing that astrocytes control behavioral performance by targeting the CA1[->]ACC projection. Specifically, that Gq- and Gi-pathway activation affect memory differently, but do so by modulating the same mechanism. These findings illuminate the importance of astrocytes in the acquisition of fear memory and their implications on recent and remote recall.

neuroscience↗

bioRxiv2022

Engram Stability and Maturation During Systems Consolidation Underlies Remote Memory

Remote memories play an important role in how we perceive the world and are rooted in ensembles in the CA1 and ACC, however the evolution of these components during systems consolidation has not yet been comprehensively addressed. By applying transgenic approaches for ensemble identification, CLARITY, retro-AAV and rabies virus for circuit mapping, and chemogenetics for functional interrogation, we addressed the dynamics of CA1-ACC ensembles and their connectivity as well as the contribution of astrocytes to the process. We found that the CA1 engrams remain stable between recent and remote recall, and, the inhibition of the engram for recent recall during remote recall functionally impairs memory. We also found that the new cells in the remote recall engram in the CA1 are not added randomly, but differ according to their connections: First, the anterograde CA1 [->] ACC engram cell projection grows larger. Second, in the retrograde projections, the ACC reduces input to CA1 engram cells, while input from the entorhinal cortex and paraventricular nucleus of the thalamus increases. Finally, we found that activating CA1 astrocytes during acquisition improves recent but not remote recall, and that CA1 [->] ACC projecting cells are recruited earlier when the astrocytes are stimulated. Our results shine fresh light on systems consolidation by providing a deeper understanding of engram stability and maturation in the transition from recent to remote memory.

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↗

bioRxiv2020

Features Of Hippocampal Astrocytic Domains And Their Spatial Relation To Excitatory And Inhibitory Neurons

The mounting evidence for the involvement of astrocytes in neuronal circuits function and behavior stands in stark contrast to the lack of detailed anatomical description of these cells and the neurons in their domains. To fill this void, we imaged >30,000 astrocytes in cleared hippocampi, and employed converging genetic, histological and computational tools to determine the elaborate structure, distribution and neuronal content of astrocytic domains. First, we characterized the spatial distribution of >19,000 astrocytes across CA1 lamina, and analyzed the detailed morphology of thousands of reconstructed domains. We then determined the excitatory content of CA1 astrocytes, averaging above 13 pyramidal neurons per domain and increasing towards CA1 midline. Finally, we discovered that somatostatin neurons are found in close proximity to astrocytes, compared to parvalbumin and VIP inhibitory neurons. This resource expands our understanding of fundamental hippocampal design principles, and provides the first quantitative foundation for neuron-astrocyte interactions in this region.

neuroscience↗

bioRxiv2019

Astrocytes Contribute to Remote Memory Formation by Modulating Hippocampal-Cortical Communication During Learning

The consolidation and retrieval of remote memories depend on the coordinated activity of the hippocampus and frontal cortices. However, the exact time at which these regions are recruited to support memory and the interactions between them are still debated. Astrocytes can sense and modify neuronal activity with great precision, but their role in cognitive function has not been extensively explored. To investigate the role of astrocytes in remote memory we expressed the Gi-coupled receptor hM4Di in CA1 astrocytes, allowing their manipulation by a designer drug. We discovered that astrocytic modulation during learning resulted in a specific impairment in remote, but not recent, memory recall, accompanied by decreased neuronal activity in the anterior cingulate cortex (ACC) during retrieval. We revealed a massive recruitment of ACC-projecting neurons in CA1 during memory acquisition, accompanied by activation of ACC neurons. Astrocytic Gi activation disrupted CA3 to CA1 communication in-vivo, and reduced the downstream response in the ACC. This same manipulation in behaving mice induced a projection-specific inhibition of ACC-projecting CA1 neurons during learning, consequently preventing the recruitment of the ACC. Our findings suggest that the foundation of remote memory is established in the ACC during acquisition, engaging a distinct process from the one supporting consolidation of recent memory. Furthermore, the mechanism underlying remote memory involves projection-specific functions of astrocytes in regulating neuronal activity.

neuroscience↗