Contribution of AMPA, NMDA, and GABA_AReceptors to Temporal Pattern of Postsynaptic Responses in the Inferior Colliculus of the Rat

Abstract

The central nucleus of the inferior colliculus (ICC) is a major site of synaptic interaction in the central auditory system. To understand how ICC neurons integrate excitatory and inhibitory inputs for processing temporal information, we examined postsynaptic responses of ICC neurons to repetitive stimulation of the lateral lemniscus at 10 -100 Hz in rat brain slices. The excitatory synaptic currents mediated by AMPA and NMDA receptors and the inhibitory current mediated by GABA A receptors were pharmacologically isolated and recorded by whole-cell patch-clamp techniques. The response kinetics of AMPA receptor-mediated EPSCs and GABA A receptor-mediated IPSCs were similar and much faster than those of NMDA receptor-mediated EPSCs. AMPA EPSCs could follow each pulse of stimulation at a rate of 10 -100 Hz but showed response depression during the course of repetitive stimulation. GABA A IPSCs could also follow stimulus pulses over this frequency range but showed depression at low rates and facilitation at higher rates. NMDA EPSCs showed facilitation and temporal summation in response to repetitive stimulation, which was most pronounced at higher rates of stimulation. GABA A inhibition suppressed activation of NMDA receptors and reduced both the degree of AMPA EPSC depression and the extent of temporal summation of NMDA EPSCs. The results indicate that GABA A receptor-mediated inhibition plays a crucial role in maintaining the balance of excitation and inhibition and in allowing ICC neurons to process temporal information more precisely.

Contribution of NMDA and AMPA Receptors to Temporal Patterning of Auditory Responses in the Inferior Colliculus

“…In the inferior colliculus (IC), studied here, in vitro and in vivo studies generally reinforce the view that AMPARs and NMDARs mediate early and late elements, respectively, of temporal response patterns (Faingold et al, 1989;Feldman and Knudsen, 1994;Zhang and Kelly, 2001;Ma et al, 2002;Wu et al, 2004). However, in vivo blockade of AMPARs in IC does not always eliminate early spikes as expected (Feldman and Knudsen, 1994;Zhang and Kelly, 2001), and in vitro studies of other systems reveal fast postsynaptic responses mediated by NMDARs (D'Angelo et al, 1990;Wolszon et al, 1997).…”

“…F, For each latency group, spike reduction by CPP for onset units and the early component of sustained responses were similar. lated to effectiveness in activating synaptic targets (Blitz and Regehr, 2003), temporal integration (Zhang and Kelly, 2001;Wu et al, 2004), and enhanced responses to coincident input (Binns, 1999). This study suggests that the NMDARs may be used to regulate first-spike latency, an essential component in the analysis of temporally distributed elements in sensory stimuli and a necessary feature in matching the timing of sensory-evoked neural activity to appropriate behavioral responses (Casseday and Covey, 1996).…”

“…In some neurons, NMDAR blockade eliminated all spikes occurring as early as 6 ms after stimulus onset. Although we cannot know the latencies of inputs to such neurons, it is clear that their NMDAR-mediated currents must activate much more quickly than reported rise times of ϳ23-27 ms for NMDAR excitatory postsynaptic potentials in the rat IC Wu et al, 2004). Elsewhere, in vitro and in vivo experiments support the presence of fast-acting NMDAR currents (D'Angelo et al, 1990;Wolszon et al, 1997).…”

Rapid Neural Adaptation to Sound Level Statistics

“…Furthermore, synaptic depression in the IC in vitro occurs over hundreds of milliseconds (Wu et al, 2004); therefore, adaptation of synaptic strength within the IC itself may contribute to the rapid effects we describe. Alternatively, the rapid adaptation of IC responses after an increase in mean level is suggestive of medial olivocochlear (MOC) efferent effects, which modulate outer hair cell activity over a similar time course (Boyev et al, 2002;Backus and Guinan, 2006;Guinan, 2006) and indeed adjust ANF rate level functions (Guinan and Stankovic, 1996).…”

Serotonergic modulation of inhibitory synaptic transmission in mouse inferiorcolliculus

“…3D) highlights the significant difference in the magnitude of serotonergic modulation on these two inhibitory neurons. In this study, we compared serotonergic modulation on two important inhibitory systems in the IC, namely GABAergic and glycinergic neurons, using maintaining the balance between excitation and inhibition and in allowing IC neurons to process temporal information more precisely (9). Moreover, approximately two-thirds of GABA-positive neurons are associated with serotonin receptors (7).…”