RT Journal Article SR Electronic T1 Dense Computer Replica of Cortical Microcircuits Unravels Cellular Underpinnings of Auditory Surprise Response JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.05.31.126466 DO 10.1101/2020.05.31.126466 A1 Oren Amsalem A1 James King A1 Michael Reimann A1 Srikanth Ramaswamy A1 Eilif Muller A1 Henry Markram A1 Israel Nelken A1 Idan Segev YR 2020 UL http://biorxiv.org/content/early/2020/06/01/2020.05.31.126466.abstract AB The nervous system is notorious for its strong response evoked by a surprising sensory input, but the biophysical and anatomical underpinnings of this phenomenon are only partially understood. Here we utilized in-silico experiments of a biologically-detailed model of a neocortical microcircuit to study stimulus specific adaptation (SSA) in the auditory cortex, whereby the neuronal response adapts significantly for a repeated (“expected”) tone but not for a rare (“surprise”) tone. SSA experiments were mimicked by stimulating tonotopically-mapped thalamo-cortical afferents projecting to the microcircuit; the activity of these afferents was modeled based on our in-vivo recordings from individual thalamic neurons. The modeled microcircuit expressed naturally many experimentally-observed properties of SSA, suggesting that SSA is a general property of neocortical microcircuits. By systematically modulating circuit parameters, we found that key features of SSA depended on synergistic effects of synaptic depression, spike frequency adaptation and recurrent network connectivity. The relative contribution of each of these mechanisms in shaping SSA was explored, additional SSA-related experimental results were explained and new experiments for further studying SSA were suggested.Competing Interest StatementThe authors have declared no competing interest.