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This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 102/5/2627    most recent 00111.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Pliss, L. Articles by Xu-Friedman, M. A. PubMed PubMed Citation Articles by Pliss, L. Articles by Xu-Friedman, M. A.

RESEARCH-ARTICLE

Context-Dependent Effects of NMDA Receptors on Precise Timing Information at the Endbulb of Held in the Cochlear Nucleus

Department of Biological Sciences, State University of New York, Buffalo, New York

Submitted 6 February 2009; accepted in final form 31 August 2009

ABSTRACT

Many synapses contain both AMPA receptors (AMPAR) and N-methyl-D-aspartate receptors (NMDAR), but their different roles in synaptic computation are not clear. We address this issue at the auditory nerve fiber synapse (called the endbulb of Held), which is formed on bushy cells of the cochlear nucleus. The endbulb refines and relays precise temporal information to nuclei responsible for sound localization. The endbulb has a number of specializations that aid precise timing, including AMPAR-mediated excitatory postsynaptic currents (EPSCs) with fast kinetics. Voltage-clamp experiments in mouse brain slices revealed that slow NMDAR EPSCs are maintained at mature endbulbs, contributing a peak conductance of around 10% of the AMPAR-mediated EPSC. During repetitive synaptic activity, AMPAR EPSCs depressed and NMDAR EPSCs summated, thereby increasing the relative importance of NMDARs. This could impact temporal precision of bushy cells because of the slow kinetics of NMDARs. We tested this by blocking NMDARs and quantifying bushy cell spike timing in current clamp when single endbulbs were activated. These experiments showed that NMDARs contribute to an increased probability of firing, shorter latency, and reduced jitter. Dynamic-clamp experiments confirmed this effect and showed it was dose-dependent. Bushy cells can receive inputs from multiple endbulbs. When we applied multiple synaptic inputs in dynamic clamp, NMDARs had less impact on spike timing. NMDAR conductances much higher than mature levels could disrupt spiking, which may explain its downregulation during development. Thus mature NMDAR expression can support the conveying of precise temporal information at the endbulb, depending on the stimulus conditions.