Biology subjects

Tsimring, K.

Publications and source records attributed to Tsimring, K..

4 recordsLinked to original sources

bioRxiv2026

Eye-specific drive and binocular suppression in mouse visual cortex during critical period development

A key function of cortical sensory circuits is to integrate information from multiple sources to build a unified representation of the external environment. The binocular region of the mouse primary visual cortex (bV1) is a valuable model for studying sensory integration, as visual response properties of inputs from the contralateral (contra) and ipsilateral (ipsi) eye onto bV1 neurons become matched to one another over development. While the alignment of visual responses from each eye during this developmental critical period has been well-characterized, it remains unclear how this interocular alignment influences, and is influenced by, the binocularly driven responses of bV1 neurons. Here, we recorded the monocular and binocular visual response properties of layer 2/3 bV1 neurons by performing chronic two-photon calcium imaging at multiple time points spanning the ocular-dominance critical period. We found that ipsi driven responses strengthened in bV1 neurons alongside a concurrent increase in binocular suppression. Binocular tuning properties were more strongly aligned with contra responses than with ipsi responses throughout development but became progressively better matched to ipsi responses. Additionally, the explained variance of ipsi input to predicting binocular tuning increased. In chronically tracked bV1 neurons, the preferred orientation of ipsi eye driven responses was less stable than that of contra eye driven responses, and in well-tuned stable binocular neurons, ipsi and contra preferences became progressively better matched. Using population-based decoding analyses, we found that while monocular and binocular visual encoding remained stable, there was increased generalizability between visual encoding by binocular and ipsi eye driven responses. Overall, our data suggest a reciprocal interaction between ipsi development and binocular responses, such that ipsi visual inputs dynamically structure excitatory as well as putative inhibitory drive onto binocular neurons during the critical period to generate the circuitry that implements integrated binocular vision.

neuroscience↗

bioRxiv2026

nELAVL phosphorylation by CDKL5 regulates inter-condensates composition and communication to promote experience-dependent maturation of the visual cortex

Mutations in Cyclin-Dependent Kinase-Like 5 (CDKL5) cause CDKL5 deficiency disorder (CDD), an X-linked neurodevelopmental condition. Through a phosphoproteomic screen, we identified the neuron-specific nELAVL family of RNA-binding proteins as direct activity-dependent substrates of CDKL5. In support of this regulatory axis, single-nuclei transcriptomics of Cdkl5 knockout (KO) cortices revealed an enriched reduction in activity-dependent mRNAs. Mechanistically, we show that nELAVL proteins undergo phase separation to form biomolecular condensates, the size of which is gated by CDKL5 phosphorylation. Loss of CDKL5 leads to enlarged nELAVL condensates, which exhibit reduced binding affinity for the target mRNA Fos, resulting in its accelerated degradation. This disruption extends to inter-condensate communication: phosphodeficient nELAVL show diminished interaction with P-bodies, which themselves become enlarged in CDD mutant iNeurons. Functionally, the absence of nELAVL phosphorylation recapitulates the deficits in experience-dependent visual function observed in Cdkl5 KO mice. Our findings establish a critical molecular mechanism by which CDKL5-mediated phosphorylation governs mRNA metabolism by tuning the properties of nELAVL condensates and their communication with other biomolecular condensates, ultimately promoting experience-dependent maturation of the visual cortex.

neuroscience↗

bioRxiv2024

The noncoding circular RNA circHomer1 regulates developmental experience-dependent plasticity in mouse visual cortex

Circular RNAs (circRNAs) are a class of closed-loop, single stranded RNAs whose expression is particularly enriched in the brain. Despite this enrichment and evidence that the expression of circRNAs are altered by synaptic development and in response to synaptic plasticity in vitro, the regulation by and function of the majority of circRNAs in experience-dependent plasticity in vivo remain unexplored. Here, we employed transcriptome-wide analysis comparing differential expression of both mRNAs and circRNAs in juvenile mouse primary visual cortex (V1) following monocular deprivation (MD), a model of experience-dependent developmental plasticity. Among the differentially expressed mRNAs and circRNAs following 3-day MD, the circular and the activity-dependent mRNA forms of the Homer1 gene, circHomer1 and Homer1a respectively, were of interest as their expression changed in opposite directions: circHomer1 expression increased while the expression of Homer1a decreased following 3-day MD. Knockdown of circHomer1 delayed the depression of closed-eye responses normally observed after 3-day MD. circHomer1-knockdown also led to a reduction in average dendritic spine size prior to MD but critically there was no further reduction after 3-day MD, consistent with impaired structural plasticity. circHomer1-knockdown also prevented the reduction of surface AMPA receptors after 3-day MD. Synapse-localized puncta of the AMPA receptor endocytic protein Arc increased in volume after MD but were smaller in circHomer1-knockdown neurons, suggesting that circHomer1 knockdown impairs experience-dependent AMPA receptor endocytosis. Thus, the expression of multiple circRNAs are regulated by experience-dependent developmental plasticity, and our findings highlight the essential role of circHomer1 in V1 synaptic development and experience-dependent plasticity. Significance StatementCircular RNAs (circRNAs) are a class of closed-loop RNAs formed through back-splicing of exon and/or intron junctions. Initially considered as byproducts of aberrant RNA splicing with limited function, recent studies have implicated circRNAs in various neurological disorders. Despite their abundant expression in the brain, the role of circRNAs in experience-dependent plasticity remains poorly understood. We conducted an in vivo transcriptome analysis of circRNAs whose expression was regulated by experience-dependent plasticity in the mouse visual cortex and highlight circHomer1, a circRNA derived from the Homer1 gene, as a circRNA critical for synaptic development and experience-dependent plasticity in vivo.

neuroscience↗

bioRxiv2017

Learning-induced sequence reactivation during sharp-wave ripples: a computational study

During sleep, memories formed during the day are consolidated in a dialogue between cortex and hippocampus. The reactivation of specific neural activity patterns - replay - during sleep has been observed in both structures and is hypothesized to represent a neuronal substrate of consolidation. In the hippocampus, replay happens during sharp wave - ripples (SWR), short bouts of excitatory activity in area CA3 which induce high frequency oscillations in area CA1. In particular, recordings of hippocampal cells which spike at a specific location ( place cells) show that recently learned trajectories are reactivated during SWR in the following sleep SWR. Despite the importance of sleep replay, its underlying neural mechanisms are still poorly understood.\n\nWe developed a model of SWR activity, to study the effects of learning-induced synaptic changes on spontaneous sequence reactivation during SWR. The model implemented a paradigm including three epochs: Pre-sleep, learning and Post-sleep activity. We first tested the effects of learning on the hippocampal network activity through changes in a minimal number of synapses connecting selected pyramidal cells. We then introduced an explicit trajectory-learning task to the model, to obtain behavior-induced synaptic changes. The model revealed that the recently learned trajectory reactivates during sleep more often than other trajectories in the training field. The study predicts that the gain of reactivation rate during sleep following vs sleep preceding learning for a trained sequence of pyramidal cells depends on Pre-sleep activation of the same sequence, and on the amount of trajectory repetitions included in the training phase.

neuroscience↗