Biology subjects

Gilabert-Juan, J.

Publications and source records attributed to Gilabert-Juan, J..

3 recordsLinked to original sources

bioRxiv2025

Convergent pathways with impaired inhibition at the frontal cortex are the outcome of differential alterations in the male and female schizophrenia model

Schizophrenia is associated with impaired inhibitory neurotransmission and disrupted synaptic plasticity in the medial prefrontal cortex (mPFC), yet the biological mechanisms underlying these deficits may differ between sexes. Here, we used a double-hit rat model, combining perinatal NMDA receptor blockade and post-weaning social isolation, to dissect sex-specific alterations in inhibitory circuit maturation, synaptic plasticity, and prefrontal function. Male double-hit rats exhibited robust schizophrenia-like behaviors, reduced parvalbumin (PV), OTX2, and perineuronal net (PNN) expression, decreased GAD67 levels, and increased DNA damage in PV interneurons, together indicating impaired inhibitory maturation and weakened plasticity. In contrast, females showed milder behavioral deficits but displayed increased PV and OTX2 intensities, enhanced cFos activation in excitatory neurons, and transcriptomic upregulation of glutamatergic, GABAergic, and synapse assembly pathways, suggesting a state of heightened or dysregulated plasticity. Despite these divergent molecular trajectories, in vivo electrophysiology revealed a shared functional endpoint in both sexes: a shift from paired-pulse inhibition to facilitation during basolateral amygdala-evoked responses, reflecting impaired GABAB-mediated inhibitory feedback. Pharmacological blockade of GABAB, but not GABAA, receptors reproduced this phenotype, identifying GABAB signaling as a key mechanism underlying cortical disinhibition. Altogether, our findings reveal that males and females reach convergent prefrontal inhibitory deficits through sex-specific molecular pathways, underscoring the importance of sex as a biological variable in the pathophysiology and treatment of schizophrenia.

neuroscience↗

bioRxiv2025

Comparative Analysis of FOXP2 Expression in the Thalamus of Mice, Rats, and Macaques: Implications for the Evolution of Language Circuits.

FOXP2 is a transcription factor essential for the development and function of neural circuits involved in language. Although its expression has been extensively characterized in the cortex and basal ganglia, its organization within the adult thalamus remains poorly understood. In this study, we present a comparative analysis of FoxP2 protein expression across thalamic nuclei in mice, rats, and macaques, with a focus on nuclei associated with higher-order cognitive functions and language-related circuits in humans. We found that FoxP2 is expressed in most thalamic nuclei across species, with a consistent absence in the reticular nucleus and zona incerta. Expression was highest in midline and intralaminar nuclei, whereas the anterior group showed low and variable expression among species. Macaques exhibited broader and, in some nuclei, more intense FoxP2 expression, particularly in associative regions such as the pulvinar, lateral geniculate, and parts of the ventral group, indicating increased specialization of thalamocortical pathways. This distribution suggests a conserved role for FoxP2 in shaping thalamic circuits supporting sensorimotor integration, attention, memory, and linguistic processing. Phylogenetic comparisons further indicate that enhanced FoxP2 expression in associative thalamic territories in primates, likely intensified in humans, may have contributed to the evolution of neural circuits required for speech and language. These findings provide molecular and anatomical insights into how FoxP2 helps organize thalamocortical networks relevant both to language function and to neuropsychiatric disorders involving thalamocortical dysconnectivity.

neuroscience↗

bioRxiv2019

Non-cell autonomous OTX2 transcription factor regulates anxiety-related behaviors in the mouse

The Otx2 homeoprotein transcription factor is expressed in the dopaminergic neurons of the ventral tegmental area, a mesencephalic nucleus involved in the control of complex behaviors through its projections to limbic structures, including the ventral hippocampus, amygdala, nucleus accumbens and medial prefrontal cortex. We find adult mice heterozygous for Otx2 show anxiolysis-like phenotype in light-dark box and elevated plus maze paradigms. However, the number of dopaminergic neurons, the integrity of their axons, their projection patterns in target structures, and the amounts of dopamine and dopamine metabolites in targets structures were not modified. Because OTX2 is expressed by the choroid plexus, secreted into cerebrospinal fluid and transferred to parvalbumin interneurons of the cortex, hippocampus, and amygdala, we investigated if this phenotype could result from the decreased synthesis of OTX2 in the choroid plexus. Indeed, the anxiolysis-like phenotype was partially recapitulated in the Otx2+/AA and scFvOtx2tg/0 choroid-plexus dependent non-cell-autonomous OTX2 loss of function mouse models. Furthermore, the phenotype was reversed by the overexpression of Otx2 specifically in choroid plexus of adult Otx2 heterozygous mice. Taken together, OTX2 synthesis by the choroid plexus followed by its secretion into the cerebrospinal fluid is an important regulator of the anxiety phenotype in the mouse.

neuroscience↗