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NAIR, R. R.

Publications and source records attributed to NAIR, R. R..

2 recordsLinked to original sources

Enrichment of specific GABAergic neuronal types in the mouse perirhinal cortex

GABAergic neurons represent 10-15% of the neuronal population of the cortex but exert a powerful control over information flow in cortical circuits. GABAergic neurons show an extraordinary diversity in their morphology, physiology, molecular markers and connectivity. This diversity allows GABAergic neurons to participate in a wide variety of microcircuit motifs. The diversity of GABAergic neurons has been shown to be conserved across cortical regions. The GABAergic population can be broadly divided in three major classes parvalbumin, somatostatin and 5HT3aR groups. The largest GABAergic class in the cortex is represented by the parvalbumin-expressing fast-spiking neurons, which provide powerful somatic inhibition to their postsynaptic targets. Recently, the density of parvalbumin-expressing neurons has been shown to be lower in associative areas of the mouse cortex, including the perirhinal cortex, as compared to sensory and motor areas. In the present study we investigated whether this reduction in parvalbumin-expressing neurons leads to a decreased GABAergic population, or to an enrichment of other GABAergic cell-types. We found that the GABAergic population of the perirhinal cortex is comparable to that of a primary sensory area, and it is enriched of neurons belonging to the 5HT3aR group. We also demonstrate that, despite the low density of parvalbumin-expressing neurons, the perirhinal cortex contains a comparable population of fast-spiking neurons, most of which do not express parvalbumin. Our results demonstrate a yet uncharacterized diversity within the fast-spiking population across cortical regions.

neuroscience↗

Modelling functional human neuromuscular junctions in a differentially-perturbable microfluidic environment, validated through recombinant monosynaptic pseudotyped ΔG-rabies virus tracing

Compartmentalized microfluidic culture systems provide new perspectives in in vitro disease modelling as they enable co-culture of different relevant cell types in interconnected but fluidically isolated microenvironments. Such systems are thus particularly interesting in the context of in vitro modelling of mechanistic aspects of neurodegenerative diseases such as amyotrophic lateral sclerosis, which progressively affect the function of neuromuscular junctions, as they enable the co-culture of motor neurons and muscle cells in separate, but interconnected compartments. In combination with cell reprogramming technologies for the generation of human (including patient-specific) motor neurons, microfluidic platforms can thus become important research tools in preclinical studies. In this study, we present the application of a microfluidic chip with a differentially-perturbable microenvironment as a platform for establishing functional neuromuscular junctions using human induced pluripotent stem cell derived motor neurons and human myotubes. As a novel approach, we demonstrate the functionality of the platform using a designer pseudotyped {Delta}G-rabies virus for retrograde monosynaptic tracing.\n\nGraphical abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=186 SRC=\"FIGDIR/small/745513v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (91K):\norg.highwire.dtl.DTLVardef@d34487org.highwire.dtl.DTLVardef@3804b8org.highwire.dtl.DTLVardef@1be0389org.highwire.dtl.DTLVardef@1da414c_HPS_FORMAT_FIGEXP M_FIG Functional neuromuscular junction in a microfluidic chip\n\n(a) Overview of microfluidic chip. Human iPS cell-derived motor neuron aggregates (spheroids indicated by black arrows) are seeded in the three lateral compartments of the chip, while human myotubes (white arrows) are seeded in the middle compartment.\n\n(b) Directed connectivity and retrograde virus tracing. Outgrowing axons (yellow arrow) from the motor neuron aggregate enter the directional axon tunnels (grey rectangles) and form connections with the myotubes (white arrow) within the opposite compartment. Addition of a designer monosynaptic pseudotyped {Delta}G-rabies virus to the myotube compartment, infects the myotubes (green) expressing an exogenous receptor (TVA) and rabies glycoprotein (G), subsequently making infectious viruses that are retrogradely transported through the motor neuron axons (green arrow) back to the neuronal cell bodies within the aggregate, validating neuromuscular junction functionality.\n\nC_FIG

neuroscience↗