A key underlying principle in brain circuity is input-specificity. For example, in prefrontal cortex – a region crucial for decision making – synaptic input from thalamus confers distinct information from local cortical input. This is thought to be made possible by differences in the molecular make-up of the synapses that make up each input. In this project we will develop SynFinity (Synaptic tandem affinity with infinite possibility), a technique that will allow high-throughput molecular characterisation of synaptic connections with input-specificity for the first time. This project combines expertise in systems neuroscience and input-specific anatomy (MacAskill) and molecular biology and proteomics (Gold).
Wee, R. W. S. & MacAskill, A. F. Biased Connectivity of Brain-wide Inputs to Ventral Subiculum Output Neurons. Cell Reports 30, 3644-3654.e6 (2020).
MacAskill AF, Cassel JM, Carter AG. Cocaine exposure reorganizes cell type- and input-specific connectivity in the nucleus accumbens. Nat Neurosci. 2014;17(9):1198-1207
Roux KJ, Kim DI, Raida M, Burke B. A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells. J Cell Biol. 2012;196(6):801-810
Uezu A, Kanak DJ, Bradshaw TW, et al. Identification of an elaborate complex mediating postsynaptic inhibition. Science. 2016;353(6304):1123-1129
Wee RWS, MacAskill AF. Biased Connectivity of Brain-wide Inputs to Ventral Subiculum Output Neurons. Cell Rep. 2020;30(11):3644-3654.e6
Walker-Gray R, Stengel F, Gold MG. Mechanisms for restraining cAMP-dependent protein kinase revealed by subunit quantitation and cross-linking approaches. PNAS 2017;114(39):10414-10419