title: Development of chloride-mediated inhibition in neurons of the anteroventral cochlear nucleus of gerbil (Meriones unguiculatus).
abstract: At the initial stages in neuronal development, GABAergic and glycinergic neurotransmission exert depolarizing responses, assumed to be of importance for maturation, which in turn shift to hyperpolarizing in early postnatal life due to development of the chloride homeostasis system. Spherical bushy cells (SBC) of the mammalian cochlear nucleus integrate excitatory glutamatergic inputs with inhibitory (GABAergic and glycinergic) inputs to compute signals that contribute to sound localization based on interaural time differences. To provide a fundamental understanding of the properties of GABAergic neurotransmission in mammalian cochlear nucleus, we investigated the reversal potential of the GABA-evoked currents (E GABA) by means of gramicidin-perforated-patch recordings in developing SBC. The action of GABA switches from depolarizing to hyperpolarizing by the postnatal day 7 due to the negative shift in E GABA. Furthermore, we studied the expression pattern of the K+-Cl(-)-extruding cotransporter KCC2, previously shown to induce a switch from neonatal Cl(-) efflux to the mature Cl(-) influx in various neuron types, thereby causing a shift from depolarizing to hyperpolarizing GABA action. The KCC2 protein is expressed in SBC already at birth, yet its activity is attained toward the end of the first postnatal week as indicated by pharmacological inhibition. Interruption of the Cl(-) extrusion by [(dihydroindenyl)oxy] alkanoic acid or furosemide gradually shifted E(GABA) in positive direction with increasing maturity, suggesting that KCC2 could be involved in maintaining low [Cl(-)]i after the postnatal day 7 thereby providing the hyperpolarizing Cl(-)-mediated inhibition in SBC.
authors.affiliation: Institute of Biology II, Faculty of Biosciences, Pharmacy and Psychology, University of Leipzig, Talstr. 33, D-04103 Leipzig, Germany.
authors.forename: Ivan
authors.initials: I
authors.lastname: Milenković
authors.forename: Mirko
authors.initials: M
authors.lastname: Witte
authors.forename: Rostislav
authors.initials: R
authors.lastname: Turecek
authors.forename: Marco
authors.initials: M
authors.lastname: Heinrich
authors.forename: Thomas
authors.initials: T
authors.lastname: Reinert
authors.forename: Rudolf
authors.initials: R
authors.lastname: Rübsamen
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000502:physiology; D002712:Chlorides / Q000494:pharmacology*; D017626:Cochlear Nucleus / Q000502:physiology*; D004594:Electrophysiology / Q000379:methods; D005665:Furosemide / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D005849:Gerbillinae; D005998:Glycine / Q000502:physiology; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011724:Pyridazines / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000502:physiology
chemical_list: D002712:Chlorides; D018756:GABA Antagonists; D011724:Pyridazines; D011963:Receptors, GABA-A; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D005665:Furosemide; C049853:gabazine; D005998:Glycine