Neurobiology
Neuroscience, Brain and Cognition
Research in this field is carried out by several investigators using an innovative and multidisciplinary approach, employing state-of-the-art methods to address fundamental questions in neurobiology, cognition, and behavior.
Spatial navigation and memory
One of the central objectives of systems neuroscience is to understand the neural mechanisms of learning and memory, much of which critically depends on the hippocampus. Understanding the normal process of memory formation in the hippocampal region will facilitate our ability to mitigate the profound memory loss caused by damage to the entorhinal cortex and the hippocampus in Alzheimer’s disease, stroke, traumatic brain injury and epilepsy. Space is the most conspicuous functional correlate of rodent hippocampal neurons. A prominent theory posits that hippocampal “place cells” constitute a spatial framework and that items and events of experience are organized within this spatial framework to create a “cognitive map”. Cortical inputs to the hippocampus are channelled through the lateral entorhinal cortex (LEC) and the medial entorhinal cortex (MEC). While MEC encodes path-integration-derived spatial information, we have recently shown that LEC encodes sensory-derived spatial and nonspatial information.
Such sensory-derived information is critical to the cognitive map for anchoring the spatial representation to the real world using landmarks and storing (and processing) nonspatial information in the context of spatial information. The laboratory records the activities of neurons in different parts of the hippocampal formation from freely moving rats to study the information these neurons carry about space, objects in space, and unique events that happen at different locations. Our past work has helped improve the understanding of how information about objects and events is represented in the context of space. Our current work at SNIoE focuses on understanding how objects, events and spatial complexity fundamentally alter the representation of space. We use a state-of-the-art wireless electrophysiology system to record neural activity from rats running in large, complex environments to answer these questions.
Investigator: Dr Sachin Deshmukh, Associate Professor, Department of Life Sciences
(A). We use tetrode (bundle of 4 insulated electrodes twisted together) to record neural activity from the brains of awake, behaving rats. Hyperdrives, designed in the lab and 3D printed, are used for accurately positioning tetrodes in target regions of the brain. (B). Place cells recorded from the hippocampus of a rat foraging in a 17 m2 environment with a partition dividing the environment into two. Grey traces on the left are the rat's trajectory; red dots are locations where the neuron fired action potentials. On the right, a firing rate map shows how the neuron changed its firing rate as a function of the rat's location. Dark blue corresponds to neurons not firing, while red corresponds to the highest firing rate. Notice how the neuron shows strong firing only in one location, signalling every time the rat is there. (C). Nonspatial (Unit 1) and spatial (Unit 2) representations in LEC in the presence of objects. Notice how unit 1 fires at objects denoted by white circles/stars, and unit 2 fires at locations away from familiar objects. This object-dependent-spatial activity is not seen in the absence of objects.
Neurobiology and biomechanics of insect behaviour
How animals extract sensory information from the external world and process it to generate appropriate motor commands to interact with their environment is a central question in neuroscience. Our lab uses insect pollination interactions to understand how animals sense their environment, integrate sensory feedback from different modalities, generate appropriate motor actions, and the effect of sensing and learning on pollination.
On a sunny evening, one often finds butterflies fluttering in our gardens, feeding from one flower before going to another. This seemingly mundane task requires expert sensorimotor control: the butterfly extends its extremely long straw-like mouthpart as it expertly hovers over a flower and explores the floral surface until it finds a very tiny hole leading to the flower nectar, even as flowers gently sway in the wind! In fact, night-time pollinators - moths perform this task even when the light levels are limiting. How do moths and butterflies perform these pollination behaviours? Our research on insect pollination asks how animals explore their environment to extract relevant sensory cues on the floral surface, how the mechanics of sensory structures and the physiology of sensory neurons help encode relevant information, how feedback from vision and touch is integrated to control the motor output and finally how the sensory ecology of insects influences pollination outcomes. We use comparative methods to ask how animals’ natural history shapes their sensory systems and behaviour. This multidisciplinary research draws upon tools from various fields, including neuroscience, animal behaviour, biomechanics, and ecology, using tools such as high-speed videography, electrophysiology combined with computational and machine learning methods, information theory, and biomechanics to study how the brain represents and processes sensory information to control movement.
Investigator: Dr Tanvi Deora: Faculty Fellow, Department of Life Sciences
(A) Moths systematically explore floral surfaces for tactile cues. (left) The tobacco hawkmoth, Manduca sexta, comes from an artificial flower with tracks on the tip of the mouthpart (in pink). (right) The mouthpart tip position relative to the flower centre reveals that moths actively and systematically explore the floral surface from the edge (radial position = 1) to the centre (radial position = 0) to the edge to extract relevant sensory cues. (B) Neuron arbours of sensors and motor neurons associated with the moth proboscis in the brain's sub-oesophagal zone (SEZ) region.
Neuroepigenetics
Adult neurogenesis has been implicated in tissue homeostasis, brain function, and a number of psychiatric diseases associated with cognition, ageing and depression. We aim to understand gene regulatory networks during adult neurogenesis using genome-wide approaches. This will be accomplished using multiple model systems, including in vitro neural stem cell culture and in vivo conditional loss/gain of function in mouse models. We also want to understand the cross-talk between epigenetic mechanisms and key signalling pathways in neuronal development. Understanding the roles played by various epigenetic regulators and their downstream effectors in neurogenesis will be helpful towards unravelling the molecular basis of pathophysiological neuronal conditions.
Investigator: Dr Sanjeev Galande: Professor and Dean, School of Natural Sciences.
Human cognition, brain imaging and neurocognitive disorders
Each of us covets a healthy life, ageing gracefully. However, neurocognitive disturbances may interfere. In the dementia area, we investigate the pathways whereby the liver/kidney, a novel therapeutic approach to neurodegenerative disease, efficaciously eliminates the brain's toxic protein amyloid. Further, we are formulating a procedure to enhance malignant cell killing and protect normal neurocognitive tissue during brain tumour radiotherapy/chemotherapy. In mental health, we assess perceptual judgmental errors and brain networks in high-stress individuals or manic-depressives. Such errors critically handicap cognitive functioning. Under ISRO sponsorship, we are enhancing an astronaut’s neuroprotection by evaluating cognitive activation levels in adverse situations so that precautionary measures are taken.
Investigator: Dr Prasun Roy, Distinguished Professor, Department of Life Sciences;
Co-Head, Shiv Nadar IoE Dassault Systemes Centre of Excellence.
(A) Neuroprotection modalities. Pathways by which toxic amyloid protein can have enhanced clearance and elimination pharmacologically (left). Clinical trial analysis of repurposed drugs for neuroinflammation, formulated by systems biology procedure (upper right). Neural progenitor cell preparation to assess neuroprotective agents (lower left). (B): Brain tumour behaviour: Transverse MRI scanning of malignant glioma tumour of the brain showing spread (upper left). Neuroimaging-based localization of the brain’s white matter fibres can translocate the cancer cells across the brain (upper right). Microscopic image of migrating cells, oriented in linear travelling direction (lower). For oncological treatment, radiotherapy planning can also be designed to include the malignancy migration route beside the main tumour. (C): Cerebral region responsible for perceptual errors in psychosis patients. Side view of tractography mapping of the brain showing nerve tracts for spatial perception (upper) and temporal perception (lower). The medial temporal area A is the node common to both pathways, showing where both streams interact abnormally in the patient.
Neuropsychiatric disorders
Depression and anxiety are recurrent psychiatric illnesses with limited success in treatment and increasing prevalence worldwide. Current treatments are focused on restoring dysregulated neurotransmitters within the brain and have several side effects. By combining the genetically amenable fruit fly, Drosophila melanogaster, and rodent models together with molecular genetics, behavioral, pharmacological, electrophysiological, and cellular approaches, we are examining how noncoding RNA pathways impact depression and anxiety. To unravel new heritable genetic loci that contribute to the pathogenesis of anxiety-like behavior in a sexually dimorphic manner, we are using a subset of the Drosophila Genetics Reference Panel (DGRP) lines for genome-wide association studies (GWAS).
Investigator: Dr. Geetanjali Chawla, Associate Professor, Department of Life Sciences