My group studies the core mechanisms of neuronal synaptic and circuit function, including activity-dependent changes in synaptic strength and circuit connectivity, in key regions of the brain that mediate memory-guided and reward-seeking behaviours. Our research scope spans from molecular and cell biology to computation and systems neuroscience and our goal is to probe the synaptic and neuronal circuit malfunctions that are caused by genetic abnormalities. We are particularly interested in the functional characterisation of genes, mutations in which are commonly found in patients with psychiatric and neurodegenerative disorders like autism spectrum disorders, schizophrenia and Alzheimer’s disease.

To accomplish our goals, we use a combination of cutting-edge tools in

• Mouse genetics
• Single-cell transcriptomics
• Gene editing
• Electrophysiology (in vivo and in vitro)
• Circuit manipulations (optogenetics, chemogenetics combined with intersectional approaches)
• Imaging
• Mouse behaviour

• Molecular coding of synapses in the hippocampus by synaptic cell adhesion molecules.
• Characterising brain circuits that mediate a “natural brake” on compulsive reward seeking
• Molecular dissection of synapses with non-glutamate excitatory receptors

• Seigneur E, Polepalli JS, Sudhof TC. Cbln2 and Cbln4 are expressed in distinct medial habenula-interpeduncular projections and contribute to different behavioral outputs. Proceedings of the National Academy of Sciences. 2018; 201811086
• Hung LW, Neuner S*, Polepalli JS*, Beier KT*, Wright M, Walsh JJ, Eastman LM, Luo L, Deisseroth K, Dolen G, Malenka R. Gating of social reward by oxytocin in the ventral tegmental area. Science. 2017; 357 (6358): 1406-1411
• Polepalli JS, Wu H, Goswami D, Halpern CH, Sudhof TC and Malenka RC. Modulation of excitation on parvalbumin interneurons by neuroligin-3 regulates the hippocampal network. Nature Neuroscience. 2017; 20(2):219-229
• Polepalli JS*, Jiang M*, Chen LY, Zhang B, Sudhof TC and Malenka RC. Conditional ablation of neuroligin-1 in CA1 pyramidal neurons blocks LTP by a cell autonomous NMDA receptor independent mechanism. Molecular Psychiatry. 2017; 22(3):375-383 (* co-first author)
• Schwartz N, Temkin P, Jurado S, Lim BK, Heifets BD, Polepalli JS and Malenka RC. Decreased motivation during chronic pain requires long-term depression in the nucleus accumbens. Science. 2014; 345(6196):535-42
• Polepalli JS*, Ahmad M*, Goswami D, Yang X, Kaesar-Woo Y, Südhof TC and Malenka RC. Postsynaptic Complexin Controls AMPA Receptor Exocytosis During LTP. Neuron. 2012; 73(2):260-7 (* co-first author)