Biology subjects

Matyas, F.

Publications and source records attributed to Matyas, F..

4 recordsLinked to original sources

bioRxiv2026

Dual thalamic drive defines the intra-amygdala wiring complexity

The amygdala plays a key role in affective behaviors by integrating incoming signals and conveying them towards subcortical output regions. Current models suggest a serial information flow within the amygdala from the lateral and basolateral towards the central subnuclei driven by incoming thalamic and cortical excitation. However, due to the lack of universally accepted parcellation principles, the precise connectivity and thus, the signal propagation within the circuit remain debated. Using a molecular-based parcellation, our subnucleus-specific anatomical and electrophysiological mapping revealed a previously overlooked complexity in the intra-amygdala wiring pattern in mice. Specifically, the intra-amygdala signal transfer relies on separate lateral thalamus-driven routes via the lateral subnucleus mostly bypassing the anterior basolateral and centrolateral subnuclei. In contrast, the anterior basolateral nucleus, innervated by the dorsal midline thalamus, supplies mostly extra-, but not intra-amygdala routes. We also demonstrated that a similar dual thalamo-cortico-amygdala organization exists in the human brain. Collectively, our findings identified unconventional amygdala wiring principles challenging the traditional serial lateral-basolateral-central stream model which can redefine our understanding of behaviorally relevant intra-amygdala computations.

neuroscience↗

bioRxiv2025

A thalamic circuit mechanism for stress-dependent modulation of REM sleep

Rapid eye movement (REM) sleep, a brain state critical for sleep quality and cortical cognition, is tightly controlled by brainstem circuits and highly sensitive to stress. Yet, how these systems interact to regulate REM sleep and its associated forebrain rhythms remains elusive. Here, we identify a thalamic hub that conveys medullary REM-promoting signals, and integrates stress inputs to regulate REM sleep. A subpopulation of paraventricular thalamic neurons that collaterally project to the cortex and nucleus accumbens (PVT[->]NAc) selectively responds to activation of medulla REM-promoting neurons, and bidirectionally modulates REM-associated theta oscillations in an activity-dependent manner. Their low-frequency activation promotes theta rhythms during REM sleep, while high-frequency activation suppresses them, mirroring the neuronal signatures of acute and chronic stress, respectively. Distinct patterns of PVT[->]NAc neurons underlie the bidirectional stress modulation of REM sleep, partly by differentially engaging prefrontal microcircuits via their collateral projections. Together, our findings uncover a thalamic integrative hub that couples sleep-regulating and stress pathways to adaptively control REM sleep expression.

neuroscience↗

bioRxiv2025

CoreTIA: a modular, statistically robust transduction inhibition assay for AAV neutralization

Adeno-associated virus (AAV) gene therapy is often limited by pre-existing neutralizing antibodies (NAbs), yet current assays for NAb detection lack standardization and rarely quantify uncertainty, complicating cross-study comparisons. We present coreTIA (core Transduction Inhibition Assay), a modular experimental protocol combined with a statistically robust analysis pipeline that delivers precise, reproducible NAb titers with quantified uncertainty for every result. coreTIAs statistical framework enables robust estimation of neutralization even when dilution series are incomplete, helping to reduce repeat testing and minimizing sample volume requirements. Evaluation and refinement of key assay parameters support consistent performance across AAV serotypes. By providing a protocol and analysis suite as an open resource, coreTIA facilitates more consistent and transparent NAb measurement, potentially aiding assay harmonization and regulatory assessment, addressing a key barrier to progress in gene therapy research and development.

immunology↗

bioRxiv2022

Molecular characteristics and laminar distribution of prefrontal neurons projecting to the mesolimbic system

Prefrontal cortical influence over the mesolimbic system - including the nucleus accumbens (NAc) and the ventral tegmental area (VTA) - is implicated in various cognitive processes and behavioral malfunctions. The functional versatility of this system could be explained by an underlying anatomical complexity; however, the detailed characterization of the medial prefrontal cortical (mPFC) innervation of the NAc and VTA is still lacking. Therefore, combining classical retrograde and conditional viral tracing techniques with multiple fluorescent immunohistochemistry, we sought to deliver a precise, cell- and layer-specific anatomical description of the cortico-mesolimbic pathways. We demonstrated that NAc- (mPFCNAc) and VTA-projecting mPFC (mPFCVTA) populations show different laminar distribution (layers 2/3-5a and 5b-6, respectively) and express different molecular markers. Specifically, calbindin and Ntsr1 are specific to mPFCNAc neurons, while mPFCVTA neurons express high levels of Ctip2 and FoxP2, indicating that these populations are mostly separated at the cellular level. We directly tested this with double retrograde tracing and Canine adenovirus type 2-mediated viral labelling and found that there is indeed minimal overlap between the two populations. Furthermore, whole-brain analysis revealed that the projection patter of these populations is also different throughout the brain. Taken together, we demonstrated that the NAc and the VTA are innervated by two, mostly non-overlapping mPFC populations with different laminar distribution and molecular profile. These results can contribute to the advancement in our understanding of mesocorticolimbic functions and its disorders in future studies.

neuroscience↗