title: Combined LTP and LTD of modulatory inputs controls neuronal processing of primary sensory inputs.
abstract: A hallmark of brain organization is the integration of primary and modulatory pathways by principal neurons. However, the pathway interactions that shape primary input processing remain unknown. We investigated this problem in mouse dorsal cochlear nucleus (DCN) where principal cells integrate primary, auditory nerve input with modulatory, parallel fiber input. Using a combined experimental and computational approach, we show that combined LTP and LTD of parallel fiber inputs to DCN principal cells and interneurons, respectively, broaden the time window within which synaptic inputs summate. Enhanced summation depolarizes the resting membrane potential and thus lowers the response threshold to auditory nerve inputs. Combined LTP and LTD, by preserving the variance of membrane potential fluctuations and the membrane time constant, fixes response gain and spike latency as threshold is lowered. Our data reveal a novel mechanism mediating adaptive and concomitant homeostatic regulation of distinct features of neuronal processing of sensory inputs.
authors.affiliation: Department of Mathematics, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Brent
authors.initials: B
authors.lastname: Doiron
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Zhao
authors.forename: Thanos
authors.initials: T
authors.lastname: Tzounopoulos
mesh_terms: D000818:Animals; D001703:Biophysics; D003056:Cochlear Nerve / Q000502:physiology; D017626:Cochlear Nucleus / Q000166:cytology*; D003198:Computer Simulation; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008959:Models, Neurological; D018408:Patch-Clamp Techniques / Q000379:methods; D011810:Quinoxalines / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline