Bharioke Laboratory

The neocortex is the seat of higher-order cognitive function in mammals. Yet, the rules by which neurons within the neocortex form connected circuits, and the way in which those connected circuits then generate our cognitive functions remain poorly understood. The Bharioke Lab seeks to explore these questions throughout the lifespan - from the embryonic formation of cortical circuits, through to their function in cognitive state changes in the adult – with the eventual goal of controlling circuit function by making targeted perturbations to circuit activity, and thereby modulating circuit dysfunction in neurological disorders.




Research:
The population activity of neurons underlies instantaneous changes in cognition. However, at slower time scales, this activity also drives plasticity – changes to the physical connectivity within our brains in response to its own activity. This means that neuronal activity provides both feedforward drive of cognitive function, as well as feedback modulation of the same circuits that generate the activity. This is one of the fundamental sources of complexity within the brain.

In the Bharioke lab, we seek to develop a computational understanding of this complexity, identifying:
1. Principles governing neuronal circuit plasticity
2. Associations between population activity and cognitive function and then
3. Building computational models to predict how changes in circuit activity will induce plastic changes to both circuit structure and function.

To obtain the data necessary for our computational understanding, we utilize two-photon microscopy to perform all-optical interrogations of cortical circuits, manipulating a subset of neurons within the circuit, while recording from others. We utilize both regular two-photon microscopes and cutting-edge acousto-optic two-photon microscopes to image neurons throughout the depth of cortex.

We perform these interrogations from embryonic development onwards, utilizing both novel methods like in vivo para-uterine imaging, as well as more traditional head-fixed imaging. We combine these optical approaches with computational simulations to build models of cortical function, enabling us to predictably manipulate the function of cortical circuits.

In the longer term, our goal is to use our computational models to manipulate circuits associated with specific cognitive dysfunctions seen in neurological disorders. With our access to early circuit development and having demonstrated that embryonic circuits are perturbed by genes associated with autism spectrum disorder (ASD), our area of focus is on neurodevelopmental disorders, including ASD – and plastic changes to early embryonic circuits.


Team:
Arjun Bharioke, PhD
Assistant Professor

Arjun did his undergraduate degree at the University of Toronto, graduating with a double major in Biochemistry and Chemical Physics (focusing on theoretical quantum mechanics) and a minor in Mathematics. With an interest in understanding how brains perform computations, he did his PhD under Mitya Chklovskii and Simon Laughlin, jointly between the University of Cambridge and HHMI's Janelia Research Campus. He worked on identifying theoretically-driven structure-function relationships in the Drosophila visual connectome. For his postdoctoral work, he transitioned to working in the more complex circuitry of the mouse cortex, working with Botond Roska in Basel, Switzerland. He focused on understanding how cortical circuits change their activity both during early development, and during the cognitive state changes associated with the loss of consciousness. To answer these questions, he learned to perform two-photon imaging and also developed a novel method to record form embryonic mouse neurons, in vivo. Now, in Charleston, his lab will be combining optical methods to interrogate circuits with computational modelling and simulations, to build a holistic understanding of how cortical circuits form, respond to changes, and generate cognitive functions.


Lab Members:
Julia Loghinov
Research Trainee

Julia earned her bachelor's degree in Neuroscience with a Computational Concentration, as well as a minor in Biomedical Engineering, from Carnegie Mellon University in 2023. During her undergrad, she conducted research under Alison Barth, exploring the neural correlates of learning and memory, and then spent a year in a research startup working on Alzheimer's drug discovery. Julia’s interests in the lab are in investigating the neural circuitry underlying consciousness.

Catherine Cadrecha
Research Trainee
Catherine completed her bachelor's degree in Neuroscience from the University of Florida in 2024. As an undergrad, she worked on analyzing machine learning models based on MRI data. Moving to Charleston, her interests in the lab are in understanding neuronal circuit plasticity, and its effect on circuit function.


Bharioke Laboratory Highlighted Publications:
https://www.cell.com/cell/fulltext/S0092-8674(23)00299-4
Munz*, Bharioke* et al. Pyramidal neurons form active, transient, multilayered circuits perturbed by autism-associated mutations at the inception of neocortex. Cell (2023).

https://www.cell.com/neuron/fulltext/S0896-6273(22)00303-8
Bharioke*, Munz* et al. General anesthesia globally synchronizes activity selectively in layer 5 cortical pyramidal neurons. Neuron (2022).
* Authors contributed equally to this work

https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1004315
Bharioke and Chklovskii. Automatic Adaptation to Fast Input Changes in a Time-Invariant Neural Circuit. PLoS Computational Biology. (2015)

https://www.nature.com/articles/nature12450
Takemura, Bharioke et al. A visual motion detection circuit suggested by Drosophila connectomics. Nature (2013).

All publications: https://scholar.google.com/citations?hl=en&user=pa-rnNMAAAAJ

For more information on the work we do in our lab, please visit https://www.bhariokelab.com