Biology subjects

Gandhi, S. P.

Publications and source records attributed to Gandhi, S. P..

4 recordsLinked to original sources

bioRxiv2026

Upregulation of Calbindin in Adult Inhibitory Neurons Reactivates Critical Period Plasticity in Mouse Visual Cortex

Critical periods are windows of peak learning performance where heightened synaptic plasticity enables fast, robust reorganization in juvenile brain circuits. Unlike adult plasticity which requires ongoing, persistent change in sensory experience, cortical representations can be rapidly changed during critical periods and have enduring effects. Transplantation of GABAergic inhibitory neurons has been shown to restore critical period plasticity to recipient circuits by triggering signalling changes within host inhibitory neurons. Here we transcriptionally profiled host inhibitory neurons in mouse primary visual cortex (V1) to detect gene expression changes during transplant-induced plasticity. Gene ontology enrichment analysis of differentially-expressed (DE) transcripts in host inhibitory neurons revealed synaptic plasticity- and inhibitory neuron development-related profiles. We assessed the protein expression of a top DE candidate, the calcium-binding protein Calbindin (Calb1), across transplant conditions and developmental stages. We found high Calb1 expression during the V1 critical period and during transplant-induced plasticity. To assess the functional significance of transplant-reactivated DE gene activity on visual cortical plasticity, we developed a set of AAVs to manipulate Calb1 expression specifically within inhibitory neurons. Using intrinsic signal imaging to measure ocular dominance plasticity, we found that Calb1 levels in V1 inhibitory neurons determine the extent of visual cortical plasticity. Our study provides evidence that direct induction of critical period-stage gene expression patterns in inhibitory neurons restores juvenile plasticity in targeted adult cortical circuits.

neuroscience↗

bioRxiv2026

Biosensor Cell Array Reveals Temporal GABA Secretion Dynamics from Pancreatic Islets

Pancreatic beta cells have the unique function of synthesizing and secreting high amounts of the inhibitory neurotransmitter {gamma}-aminobutyric acid (GABA). The mechanism of GABA secretion, whether vesicular or channel-mediated, is debated. Our study reveals surprising temporal complexity in the pattern of islet GABA secretion. We used insulin secretion modulators to demonstrate that GABA release is not directly correlated with insulin secretion. VGAT reporter mice also showed that beta cells do not express the requisite vesicular GABA transporter (VGAT) for vesicular GABA release. Instead, GABA is secreted from the cytosol in pulses by the LRRC8A/D isoform of the volume regulatory anion channel (VRAC). We further demonstrate the dynamic coordination of GABA release with calcium influx in beta cells and dependence on beta cell depolarization. These results suggest a model where GABA is released during the peaks of beta cell calcium oscillations to provide feedback which strengthens and reinforces the oscillation waveform.

physiology↗

bioRxiv2021

Subventricular zone/white matter microglia reconstitute the empty adult microglial niche in a dynamic wave

Microglia, the brains resident myeloid cells, play central roles in brain defense, homeostasis, and disease. Using sustained colony-stimulating factor 1 receptor inhibition, we report an unprecedented level of microglial depletion and establish a model system that achieves an empty microglial niche in the adult brain. We identify a myeloid cell that migrates from an important neurogenic niche, the subventricular zone, and associated white matter areas. These cells exhibit tremendous chemotaxis potential, migrating radially and tangentially in a dynamic wave and filling the brain in a distinct pattern, to fully replace the microglial-depleted brain. These repopulating cells are enriched in disease-associated microglia genes and exhibit distinct phenotypic and functional profiles to endogenous microglia. Our findings shed light on the overlapping and distinct functional complexity and diversity of myeloid cells of the CNS and provide new insight into myeloid cell dynamics in an empty microglial niche without contributions from bone marrow-derived cells.

immunology↗

bioRxiv2018

Early Visual Experience Shapes Binocularity in the Mouse Thalamocortical Pathway

Monocular deprivation (MD) during the juvenile critical period leads to long-lasting impairments in binocular function and visual acuity. The site of these changes has been widely considered to be cortical. However, recent evidence indicates that binocular integration may first occur in the dorsolateral geniculate nucleus of the thalamus (dLGN), raising the question of whether MD during the critical period may produce long-lasting deficits in dLGN binocular integration. Using in vivo two-photon Ca2+ imaging of dLGN afferents and excitatory neurons in superficial layers of primary visual cortex (V1), we demonstrate that critical-period MD leads to a persistent and selective loss of binocular dLGN inputs, while leaving spatial acuity in the thalamocortical pathway intact. Despite being few in number, binocular dLGN boutons display remarkably robust visual responses, on average twice stronger than monocular boutons, and their responses are exquisitely well-matched between the eyes. To our surprise, we found that MD leads to a profound binocular mismatch of response amplitude, spatial frequency and orientation tuning detected at the level of single thalamocortical synapses. In comparison, V1 neurons display deficits in both binocular integration and spatial acuity following MD. Our data provide the most compelling evidence to date demonstrating that following critical-period MD, binocular deficits observed at the level of V1 may at least in part originate from dLGN binocular dysfunction, while spatial acuity deficits arise from cortical circuits. These findings highlight a hitherto unknown role of the thalamus as a site for developmental refinement of binocular vision.

neuroscience↗