title: Control of neuronal excitability by NMDA-type glutamate receptors in early developing binaural auditory neurons.
abstract: Precise control of neuronal excitability in the auditory brainstem is fundamental for processing timing cues used for sound localization and signal discrimination in complex acoustic environments. In mature nucleus laminaris (NL), the first nucleus responsible for binaural processing in chickens, neuronal excitability is governed primarily by voltage-activated potassium conductances (K(VA)). High levels of K(VA) expression in NL neurons result in one or two initial action potentials (APs) in response to high-frequency synaptic activity or sustained depolarization. Here we show that during a period of synaptogenesis and circuit refinement, before hearing onset, K(VA) conductances are relatively small, in particular low-voltage-activated K(+) conductances (K(LVA)). In spite of this, neuronal output is filtered and repetitive synaptic activity generates only one or two initial APs during a train of stimuli. During this early developmental time period, synaptic NMDA-type glutamate receptors (NMDA-Rs) contain primarily the GluN2B subunit. We show that the slow decay kinetics of GluN2B-containing NMDA-Rs allows synaptic responses to summate, filtering the output of NL neurons before intrinsic properties are fully developed. Weaker Mg(2+) blockade of NMDA-Rs and ambient glutamate early in development generate a tonic NMDA-R-mediated current that sets the membrane potential at more depolarized values. Small KLVA conductances, localized in dendrites, prevent excessive depolarization caused by tonic activation of NMDA-Rs. Thus, before intrinsic properties are fully developed, NMDA-Rs control the output of NL neurons during evoked synaptic transmission.
authors: VirginiaMerrill Bloedel Hearing Research Center, School of Medicine, University of Washington, Box 357290, Seattle, WA 98195, USA.
authors: Jason Tait
authors: JT
authors: Sanchez
authors: Armin H
authors: AH
authors: Seidl
authors: Edwin W
authors: EW
authors: Rubel
authors: Andres
authors: A
authors: Barria
mesh_terms: D000200:Action Potentials; D000818:Animals; D001933:Brain Stem / Q000502:physiology*; D002642:Chick Embryo; D019706:Excitatory Postsynaptic Potentials; D018698:Glutamic Acid / Q000502:physiology; D066298:In Vitro Techniques; D009474:Neurons / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
chemical_list: D024642:Potassium Channels, Voltage-Gated; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid