★★★★★ Animal handling and behavior; ★★★★★ Stereotaxic manipulation; ★★★★★ Histology and immunostaining; ★★★★★ Transmission electron microscopy; ★★★☆☆ Electroporation; ★★★★☆ Electrophysiology; ★★★★★ Organotypic slice culture; ★★★★★ Biochemical tests; ★★★☆☆ NMR spectroscopy; ★★★★☆ Python; ★★★★☆ PowerBI; ★★★☆☆ IgorPro; ★★★★☆ Statistics; ★★★★☆ Writing

I'm a physiologist by academic training, my research interests include synaptic, behavioral and circuit level alteration in neurodegeneration like Alzheimer's disease (AD). Alzheimer's is known to characterized by extracellular amyloid plaque and intracellular neurofibrillary tangle deposition in brain parenchyma. Which is implicated with patient's cognitive impairment and have direct association with synaptic dysfunction. My present role is to unravel the synaptic machinery for 4r tauopathies and progressive supranuclear palsy in cortical and subcortical circuitry. This is a work that is being funded by Alzheimer's Association International at department of Neurobiology Care Sciences and Society, division of clinical geriatrics, Karolinska Institute with Dr Amit Kumar.

I had previously worked with Dr Christophe Mulle in the team Synapses and Neural Circuits in Behaviour at IINS (UMR5297), Bordeaux Neurocampus. My role was to unravel the morpho-funcational role of genetic risk factor phospholipase gamma 2 in AD. My PhD thesis investigated the role of non-invasive brain stimulation in animal model of AD. Thesis title: ‘‘A morphological and functional study on intracerebroventricular streptozotocin induced rat model of Alzheimer’s disease: Effect of magnetic field stimulation’’. This work was conducted in Neurophysiology and nano-medicine lab with Dr Suman Jain in All India Institute for Medical Sciences, New Delhi.

• Doctor of Philosophy Neurophysiology All India Institute for Medical Sciences, New Delhi, India (March; 2022)
• Masters in Science Human Physiology University of Calcutta, Kolkata, India (August; 2015)
• Bachelors in Science Physiology University of Calcutta, Kolkata, India (August; 2013)

• In a short project supported by short term studentship and student fellowship & skill development scheme by ICMR & DBT respectively I have looked into the potential to generate and incorporate new neurons in adult network of adult hippocampus of animals that has been exposed to extremely low intensity and low frequency magnetic field (sinusoidal, 17.96µT, 50Hz). In this project I've not only learnt the mechanism of action of magnetic field stimulation directly affecting the cognition through manipulation of adult born circuitry, but also got chance to guide two brilliant students.

• I've worked in an individual senior research fellowship program vide.45/5/2019-PHY/BMS from Indian Council of Medical Sciences at All India Institute of Medical Sciences, New Delhi from April 2019-2022 in project entitled as “Effect of Chronic Exposure to Low Intensity Magnetic Field on Streptozotocin Induced Synaptic Dysfunction and Amyloid Precursor Protein Processing in Rats' where co-PIs were Dr Suman Jain & Dr Jyotirmoy Banerjee. The idea of the project was to investigate the alteration to the dendritic architecture of the CA1 pyramidal layers of hippocampus injected with streptozotocin supported with the electrophysiological correlates of synaptic inputs with/ without sinusoidal magnetic field stimulation.

• From April 2022-2024 I had worked on the morpho-functional correlates of the genetic risk factors of Alzheimer's disease in a project with acronym GENSYNALZ from AAPG scheme from The French National Research Agency (ANR). This project is to develop tools to test the Alzheimer's risk genes in organotypic as well as acute slices to link morpho-functional relationship using transfection, microscopic and electrophysiological tools. Genes that we are targeting has been already funneled down with GWAS as well as preliminary through multi-electrode-array recordings on dissociated neuronal culture.

I work with acute slices from brains of animals transfected with AD risk genes. Therefore, I conduct single cell electroporation experiments, use viral tools for transfect neurons of choice. Recent electrophysiological experiments provide me to understand the intrinsic properties of granule cells of dentate gyrus (DG). And also, to understand the dynamics of perforant pathway-DG synaptic circuitry. Apart from electrophysiology my other responsibilities include morphological analysis of the DG cells both at dendritic as well as at spine level. To do so, I use multiple imaging platforms viz. wide-field, (epi)fluorescence and confocal microscopy.

And then for analysis I use Igor pro, Neuromatic, open-ephy-python-tool for Ephys and FIJI, Imaris, NeuroStudio and others for imaging experiments.

Previously, I used to do cognitive tasks with rodents. Also, microinjection through stereotaxic surgeries in brain areas (like hippocampus, lateral ventricles, hypothalamus etc.). Further, I did different histological tools (Nissl, Golgi-COX, Congo-red) including immunostaining for sub-cellular localization of proteins, biochemicals tools (ELISA, western blot), 1H-NMR, transmission electron microscopy.

During this period I came across different softwares related to the aforementioned tools like Ethovision XT, AnyMaze, FIJI, Neurolucida, Neurolucida-explorer, Mnova, TopSpin, Espina, webknoss, python, SPSS, graphpad etc.

Figure. 1: Representative images of the experiments that I do/ have done: Golgi-cox impregnated granular cells of DG layer of animals injected with streptozotocin (A); CA3 pyramidal cells transfected with plasmid using single cell electroporation tool (left panel) also the dendritic spine (right panel) fluororescence images were taken from immunestained organotypic slice with anti-NeuN (magenta), DAPI (blue) and anti-GFP (green, B); intrinsic biophysical properties of DG cells recorded with whole-cell current-clamp patch-clamp tool from lenti-virally infected cells with desired shRNA taken with DIC image from ephys rig (in green) step-wise current injection protocol for AP generation (second image), short-pulse current injection for action potential (third image) and paied-pulse action fecilitation frm performant path-DG circuit (fourth image, C); Morris-water-maze occupancy plot or heat map of swimming of animals injected with streptozotocin in lateral ventricles of brain: appreciable thigmotaxic behavior is seen in these animals (D); llustration representing the coronal section showing the coronal plane marking the dorsal CA1representing a detailed neuron model based on Ascoli atlas with pyramidal and interneuron (E); mossy fiber gigantic bouton reconstructed from GFP immune stained confocal image stack using Imaris (F); Fluorescence image of hilus region of DG immunestained with anti-hp-tau (red), GFP (green), DAPI for nuclui(blue, G)

Apart from doing experimental neuroscience I'm also involved in reviewing papers in peer review journals as ad-hoc reviewer in journals like

• Neurochemical research
• Journal of Chemical Neuroanatomy
• International journal of general Medicine
• Journal of Basic and Clinical Physiology and Pharmacology
• Frontiers in Neuroscience

• Rawat RS, Bhambri A, Pal M, Roy A, Jain S, Pillai B, et al. Early life stressful experiences escalate aggressive behavior in adulthood via changes in transthyretin expression and function. eLife Sciences Publications, Ltd. 2022. DOI: 10.7554/eLife.77968
• Roy A, Sharma S, Nag TC, Katyal J, Gupta YK, Jain S. Cognitive Dysfunction and Anxiety Resulting from Synaptic Downscaling, Hippocampal Atrophy, and Ventricular Enlargement with Intracerebroventricular Streptozotocin Injection in Male Wistar Rats. Neurotoxicity Research. 2022 Sep 7;40(6):2179–202. DOI: 10.1007/s12640-022-00563-x
• Sharma B, Roy A, Sengupta T, Vishwakarma LC, Singh A, Netam R, et al. Acute sleep deprivation induces synaptic remodeling at the soleus muscle neuromuscular junction in rats. Sleep. 2022 Sep 21;46(8). DOI: 10.1093/sleep/zsac229
• Coulon A, Rabiller F, Takalo M, Roy A, Martiskainen H, Siedlecki-Wullich D, Mendes T, Lemeu C, Carvalho L-I, Ehrardt A, Melo de Farias AR, Hulsman M, Najdek C, Lannette-Weimann N, Freire-Regatillo A, Amouyel P, Charbonnier C, Dols-Icardo O, Jeskanen H, Willman R-M, Kuulasmaa T, Kurki M, Hardy J, Wagner R, Heikkinen S, Holstege H, Mäkinen P, Nicolas G, Mead S, Wagner M, Ramirez A, Rauramaa T, Palotie A, Sims R, Soininen H, Swieten JV, Williams J, Bellenguez C, Grenier-Boley G, Gelle C, Lambert E, Ayral AM, Demiautte F, R. Costa M, Deforges S, Kilinc D, Mulle C, Chapuis J, Hiltunen M, Dumont J, Lambert J-C; Neuronal downregulation of PLCG2 impairs synaptic function and elicits Alzheimer disease hallmarks. bioRxiv 2024.04.29.591575; doi: https://doi.org/10.1101/2024.04.29.591575

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