Research Overview
Development and Plasticity of Neural Circuits Lay summary >>
Theme 1: The neuronal cytoskeleton
The development of neuronal connectivity and structural plasticity of neural circuits are intimately associated with cytoskeleton remodelling. We are interested in investigating the regulation of cytoskeletal dynamics in processes like axonal pathfinding (Sahasrabudhe and Ghose, 2012), arborisation, structural plasticity at synapses and mechanical homeostasis of neurons (Mutalik and Ghose, 2020).
In recent years, we have investigated new regulatory activities mediating axon guidance (Sahasrabudhe et al. 2016) and uncovered mechanisms mediating the generation of traction forces by neuronal growth cones (Ghate et al. 2020). The cytoskeleton subsystems are intimately coupled and we have identified new activities that mediate dynamic cross-talk between the actin and microtubule cytoskeletons (Kundu, Dutta et al. 2021). Our genetic studies have indicated that disruption of these novel modalities results in behavioural deficits (Nagar et al., 2020) and some have been implicated in human neurodevelopmental disorders.
Another focus has been the mechanobiology of neurons. Physical forces, like tension along neurites, are a higher-order integration of cytoskeleton and membrane dynamics and are critical for neuronal development, homeostasis and function (Mutalik and Ghose, 2020). Using novel assays, we have found that neurites are intrinsically contractile and actively maintain tension along their length (Mutalik et al, 2018). With Dr Pramod Pullarkat (RRI Bengaluru), we have recently identified that the periodic actin-spectrin skeleton in axons acts like 'shock absorbers' to protect neurons from stretch-induced damage (Dubey et al. 2020).
We use the developing chick embryo, zebrafish and rodent systems in combination with quantitative cell biology, biophysical and single-molecule approaches, live and superresolution microscopy, and behavioural analysis for these investigations.
Theme 2: Neuropeptide activity in optimising circuit function
Activities of neuropeptides form neuronal representations of internal states and tune circuit function. We are interested in the neuromodulatory functions of neuropeptides in the context of innate behaviours, like feeding responses, aggression and fear.
Using zebrafish as a model, we have identified interoceptive regions in the brain that change neuropeptide profiles under different energy states (Mukherjee et al. 2012 and Akash et al. 2014). We are currently investigating the signalling mechanisms subserving neuronal representation of internal states by neuropeptide activity (Kaniganti, Deogade et al. 2021).
In rodents, we have shown that response to predator smell is modulated by peptidergic signalling (Sharma et al. 2014 and Rale et al. 2017) and current studies are investigating the interplay between physiological states and fear responses.
In related work, we have investigated the neurogenetic underpinnings of behavioural flexibility during aggressive encounters and the establishment of social hierarchies. We find distinct cAMP signalling modalities regulating different aspects of agonistic behaviours (Chouhan et al. 2017).
In these studies, we employ a combination of behavioural analysis, activity imaging, genetics and pharmacology in rodent and zebrafish models.