Neuron-glia interactions in the brain
My lab study how neurons and glia cells interact, interconnect and integrate into the neural circuits of brain.
Our brain is the most networked organ in the entire body and consists of two equal populations of broadly classified groups of cells called neurons and glia. A single neuron or a glia (such as astrocyte) makes thousands of synaptic contacts, and thereby exhibit the highest level of cellular connectivity known to us. However, very little is known about the molecular and cellular mechanisms by which neurons and glia interconnect, and how these intricate connections are maintained and fine-tuned over our entire lifespan? However, recent advancements in genetically encoded ions and molecular sensors, optophysiology and in vivo microscopic techniques, single-cell genetics, mouse transgenics, and computational methodologies are changing the landscape of glial biology. The Agarwal laboratory uses these tools and technologies to decipher cellular connectivity and molecular pathways by which neurons and glia interact, interconnect and integrate into the neural networks. The focal aim of the laboratory is to understand the functional significance of these neuron-glia connections in the neural circuits, and their role in cognition, learning, and memory; and study how disturbances in these fine cellular interactions can contribute to various neurological and psychiatric disorders ranging from multiple sclerosis to autism.
Publications after start of funding
Venkatesh HS, Morishita W, Geraghty AC, Silverbush D, Gillespie SM, Arzt M, Tam LT, Espenel C, Ponnuswami A, Ni L, Woo PJ, Taylor KR, Agarwal A, Regev A, Brang D, Vogel H, Hervey-Jumper S, Bergles DE, Suvà ML, Malenka RC, Monje M.
Electrical and synaptic integration of glioma into neural circuits. 2019. Nature. Sep;573(7775):539-545.
Venkataramani V, Tanev DI, Strahle C, Studier-Fischer A, Fankhauser L, Kessler T, Körber C, Kardorff M, Ratliff M, Xie R, Horstmann H, Messer M, Paik SP, Knabbe J, Sahm F, Kurz FT, Acikgöz AA, Herrmannsdörfer F, Agarwal A, Bergles DE, Chalmers A, Miletic H, Turcan S, Mawrin C, Hänggi D, Liu HK, Wick W, Winkler F, Kuner T.
Glutamatergic synaptic input to glioma cells drives brain tumour progression. 2019. Nature, Sep;573(7775):532-538.
Larson VA, Mironova Y, Vanderpool KG, Waisman A, Rash JE, Agarwal A*, Bergles DE*.
Oligodendrocytes control potassium accumulation in white matter and seizure susceptibility. 2018. Elife Mar 29;7. pii: e34829. *Co-corresponding author
Travis E. Faust, Wendy Xin, Brian Lee, Amit Agarwal, Sneha Saha, Trexy Palen, Tyler Cash-Padgett, Daniel Wood, Antonello Bonci, Jed W. Fahey, Hanna Jaaro-Peled, Dwight E. Bergles, Akira Sawa
Astrocyte redox dysregulation causes prefrontal hypoactivity: sulforaphane treats non-ictal pathophysiology in ALDH7A1-mediated epilepsy. bioRxiv 796474; doi: doi.org/10.1101/796474
Seung-Wan Yoo, Amit Agarwal, Matthew D. Smith, Saja S. Khuder, Emily G. Baxi, Ajit G. Thomas, Camilo Rojas, Mohammed Moniruzzman, Barbara S. Slusher, Dwight E. Bergles, Peter A. Calabresi, Norman J. Haughey.
Inhibition of neutral sphingomyelinase-2 facilitates remyelination. bioRxiv 686287; doi: doi.org/10.1101/686287