title: A mechanistic understanding of the role of feedforward inhibition in the mammalian sound localization circuitry.
abstract: Feedforward inhibition sharpens the precision of neurons throughout ascending auditory pathways, including the binaural neurons of the medial superior olive (MSO). However, the biophysical influence of inhibition is poorly understood, particularly at higher frequencies at which the relative phase of inhibition and excitation becomes ambiguous. Here, we show in gerbil MSO principal cells in vitro that feedforward inhibition precedes direct excitation, providing a concurrent hyperpolarization and conductance shunt during EPSP summation. We show with dual-patch recordings and dynamic clamp that both the linearity and temporal fidelity of synaptic integration is improved by reducing Kv1 potassium channel conductance during inhibition, which counters membrane shunting even at high frequencies at which IPSPs sum. The reduction of peak excitation by preceding inhibition lowers spike probability, narrowing but not shifting the window for detecting binaural coincidence. The interplay between inhibition and potassium conductances thus improves the consistency and resolution of ITD coding across different frequencies.
authors.affiliation: Section of Neurobiology and Center for Learning and Memory, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Roberts
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Seeman
authors.forename: Nace L
authors.initials: NL
authors.lastname: Golding
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001306:Auditory Pathways / Q000502:physiology; D055592:Biophysical Phenomena / Q000187:drug effects / Q000502:physiology; D001703:Biophysics; D004546:Elapid Venoms / Q000494:pharmacology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D007839:Functional Laterality; D005849:Gerbillinae; D066298:In Vitro Techniques; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology; D009847:Olivary Nucleus / Q000166:cytology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D013017:Sound Localization / Q000502:physiology*
chemical_list: D004546:Elapid Venoms; D009498:Neurotoxins; D026902:Potassium Channel Blockers; C020273:dendrotoxin; D015761:4-Aminopyridine