====== Synaptic input ====== Neurons in the brain receive thousands of synaptic inputs from other neurons. Synaptic integration is the term used to describe how neurons 'add up' these inputs before the generation of a nerve impulse, or action potential. ---- The [[transformation]] of synaptic input into [[action potential]] [[output]] is a fundamental single-cell computation resulting from the complex interaction of distinct cellular morphology and the unique expression profile of [[ion channel]]s that define the cellular [[phenotype]]. Experimental studies aimed at uncovering the mechanisms of the transfer function have led to important insights, yet are limited in scope by technical feasibility, making biophysical [[simulation]]s an attractive complementary approach to push the boundaries in our understanding of cellular computation. Linaro et al. took a data-driven approach by utilizing high-resolution morphological [[reconstruction]]s and patch-clamp electrophysiology data together with a multi-objective optimization [[algorithm]] to build two [[population]]s of biophysically detailed models of murine hippocampal [[CA3]] [[pyramidal neuron]]s based on the two principal cell types that comprise this region. They evaluated the performance of these models and find that the approach quantitatively matches the cell-type-specific firing phenotypes and recapitulates the intrinsic population-level variability in the data. Moreover, they confirmed that the conductance values found by the optimization algorithm are consistent with differentially expressed [[ion channel]] genes in single-cell transcriptomic data for the two cell types. They then used these models to investigate the cell type-specific biophysical properties involved in the generation of complex-spiking output driven by synaptic input through an information-theoretic treatment of their respective transfer functions. The simulations identify a host of cell type-specific biophysical mechanisms that define the morpho-functional phenotype to shape the cellular transfer function and place these findings in the context of a role for [[bursting]] in CA3 recurrent network synchronization dynamics ((Linaro D, Levy MJ, Hunt DL. Cell type-specific mechanisms of information transfer in data-driven biophysical models of hippocampal CA3 principal neurons. PLoS Comput Biol. 2022 Apr 22;18(4):e1010071. doi: 10.1371/journal.pcbi.1010071. Epub ahead of print. PMID: 35452457.)).