Biology subjects

Reig-Viader, R.

Publications and source records attributed to Reig-Viader, R..

3 recordsLinked to original sources

bioRxiv2024

Synaptic proteome diversity is primarily driven by gene regulation of glutamate receptors and their regulatory proteins

Synapses formed by equivalent pairs of pre- and postsynaptic neurons have similar electrophysiological characteristics, belonging to the same type. However, these are generally confined to microscopic brain regions, precluding their proteomic analysis. This fact has greatly limited our ability to investigate the molecular basis of synaptic physiology. We introduce a procedure to characterise the synaptic proteome of microscopic brain regions and explore the molecular diversity among the synapses forming the trisynaptic circuit in the hippocampus. While we observe a remarkable proteomic diversity among these synapses, we also report that proteins involved in the regulation of the function of glutamate receptors are differentially expressed in all of them. Moreover, neuron-specific gene expression programs would contribute to their regulation. Here, we introduce a combined proteomics and transcriptomics analysis uncovering a previously unrecognised neuron-specific control of synaptic proteome diversity, directed towards the regulation of glutamate receptors and their regulatory proteins.

neuroscience↗

bioRxiv2021

Sublayer- and cell-type-specific neurodegenerative transcriptional trajectories in hippocampal sclerosis

Hippocampal sclerosis, the major neuropathological hallmark of temporal lobe epilepsy, is characterized by different patterns of neuronal loss. The mechanisms of cell-type specific vulnerability, their progression and histopathological classification remain controversial. Here using single-cell electrophysiology in vivo and immediate early gene expression, we reveal that superficial CA1 pyramidal neurons are overactive in epileptic rats and mice in vivo. Bulk tissue and single-nucleus expression profiling disclosed sublayer-specific transcriptomic signatures and robust microglial pro-inflammatory responses. Transcripts regulating neuronal processes such as voltage-channels, synaptic signalling and cell adhesion molecules were deregulated by epilepsy differently across sublayers, while neurodegenerative signatures primarily involved superficial cells. Pseudotime analysis of gene expression in single-nuclei and in situ validation revealed separated trajectories from health to epilepsy across cell types, and identified a subset of superficial cells undergoing a later stage in neurodegeneration. Our findings indicate sublayer- and cell type-specific changes associated with selective CA1 neuronal damage contributing to progression of hippocampal sclerosis.

neuroscience↗

bioRxiv2019

Syngap Splice Variants Display Heterogeneous Spatio-Temporal Expression And Subcellular Distribution In The Developing Mammalian Brain

The Syngap1 gene is a major regulator of synapse biology and neural circuit function. Genetic variants linked to epilepsy and intellectual disability disrupt synaptic function and neural excitability. The SynGAP protein has been involved in multiple signaling pathways and can regulate small GTPases with very different functions. Yet, the molecular bases behind this pleiotropy are poorly understood. We hypothesize that different SynGAP isoforms will mediate different sets of functions and that deciphering their spatio-temporal expression and subcellular localization will accelerate our understanding of the multiple functions performed by SynGAP. Using antibodies that detect all isoforms of SynGAP, we found that its subcellular localization changed throughout postnatal development. Consistent with previous reports, SynGAP was enriched in the postsynaptic density in the mature forebrain. However, this was age-dependent and SynGAP was predominantly found in non-synaptic locations in a period of postnatal development highly sensitive to SynGAP levels. Furthermore, we identified different expression patterns in the spatial and temporal axes for different SynGAP isoforms. Particularly noticeable was the delayed expression of SynGAP 1 isoforms, which bind to PSD-95 at the postsynaptic density, in cortex and hippocampus during the first two weeks of postnatal development. The subcellular localization of SynGAP was also isoform-dependent. While, 1 isoforms were highly enriched in the postsynaptic density, other C-terminal isoforms were less enriched or even more abundant in non-synaptic locations, particularly during the postnatal period. Thus, the regulation of expression and subcellular distribution of SynGAP isoforms may contribute to isoform-specific regulation of small GTPases, explaining SynGAP pleiotropy.

neuroscience↗