Interaction of Excitation and Inhibition in Anteroventral Cochlear Nucleus Neurons That Receive Large Endbulb Synaptic Endings

Abstract

Spherical bushy cells (SBCs) of the anteroventral cochlear nucleus (AVCN) receive their main excitatory input from auditory nerve fibers (ANFs) through large synapses, endbulbs of Held. These cells are also the target of inhibitory inputs whose function is not well understood. The present study examines the role of inhibition in the encoding of low-frequency sounds in the gerbil's AVCN. The presynaptic action potentials of endbulb terminals and postsynaptic action potentials of SBCs were monitored simultaneously in extracellular single-unit recordings in vivo. An input-output analysis of presynaptic and postsynaptic activity was performed for both spontaneous and acoustically driven activity. Two-tone stimulation and neuropharmacological experiments allowed the effects of neuronal inhibition and cochlear suppression on SBC activity to be distinguished.Ninety-one percent of SBCs showed significant neuronal inhibition. Inhibitory sidebands enclosed the high-or lowfrequency, or both, sides of the excitatory areas of these units; this was reflected as a presynaptic to postsynaptic increase in frequency selectivity of up to one octave. Inhibition also affected the level-dependent responses at the characteristic frequency. Although in all units the presynaptic recordings showed monotonic rate-level functions, this was the case in only half of the postsynaptic recordings. In the other half of SBCs, postsynaptic inhibitory areas overlapped the excitatory areas, resulting in nonmonotonic rate-level functions. The results demonstrate that the sound-evoked spike activity of SBCs reflects the integration of acoustically driven excitatory and inhibitory input. The inhibition specifically affects the processing of the spectral, temporal, and intensity cues of acoustic signals. Key words: prepotential units; endbulb of Held; cochlear suppression; neuronal inhibition; in vivo physiology; bicuculline; strychnine; gerbil; spherical bushy cells; cochlear nucleusThe cochlear nucleus consists of three subdivisions: the anteroventral cochlear nucleus (AVCN), the posteroventral cochlear nucleus, and the dorsal cochlear nucleus, each of which establishes the origins of several monaural and binaural ascending pathways (for review, see Irvine, 1986). It was believed previously that the AVCN serves primarily as a relay transmitting a highfidelity copy of the activity of the auditory nerve to more central auditory brainstem nuclei (Pfeiffer, 1966a,b;Rose et al., 1974). This was demonstrated by morphological data which show that the principal neurons of the AVCN, the spherical bushy cells (SBCs), are innervated by only two to four auditory nerve fibers (ANFs) that form large synaptic endbulbs on the somata of the neurons (Brawer and Morest, 1975;Ryugo and Sento, 1991;Bazwinsky et al., 1999). Because of this specific synaptic configuration, electrophysiological recordings using extracellular electrodes can detect the postsynaptic action potentials of SBCs together with a preceding "prepotential" (PP), indicating the presynaptic afferent ANF ...

Dynamic Fidelity Control to the Central Auditory System: Synergistic Glycine/GABAergic Inhibition in the Cochlear Nucleus

“…Considering the tonotopic organization of the AVCN (Kopp-Scheinpflug et al, 2002;Dehmel et al, 2010), the multiunit activity at the rostral pole was initially assessed with low impedance glass micropipettes (GB150F-10, Science Products, 1-5 M⍀ filled with 3M KCl) to narrow down the target area (frequencies Ͻ5 kHz). Then, juxtacellular single-unit recordings (electrodes 7-10 M⍀) were performed on spherical bushy cells, which were identified according to the characteristic waveform (Pfeiffer, 1966;Winter and Palmer, 1990;Englitz et al, 2009;Typlt et al, 2010), and the primary-like peristimulus time histogram pattern (Blackburn and Sachs, 1989).…”

“…Iontophoretic administration of glycine/GABA A -R antagonists during in vivo recordings and acoustic stimulation at units CFs deteriorated phase-coupling and increased the firing rates at higher stimulus intensities (Dehmel et al, 2010). The latter is probably due to largely overlapping excitatory and inhibitory response areas (on-CF inhibition) (Winter and Palmer, 1990;Kopp-Scheinpflug et al, 2002;Kuenzel et al, 2011). According to our results, the activation of inhibition at higher sound pressure levels might induce larger inhibitory current summation (tonic inhibition due to higher firing rate or recruitment of inputs), leading to both nonmonotonic rate-level function and tightening of phase-coupling (Dehmel et al, 2010).…”

Encoding Intensity in Ventral Cochlear Nucleus Following Acoustic Trauma: Implications for Loudness Recruitment

“…At these synapses, postsynaptic potentials are large, and the time constants of the postsynaptic neurons are short, which prevents temporal summation of synaptic events (Oertel 1985;Raman and Trussell 1992;Isaacson and Walmsley 1996). Presumably, PL and AN RLFs were similar because the operating mode of these synapses is to produce a postsynaptic spike whenever there is a presynaptic spike, as demonstrated by their complex action potentials which contain both a pre-and a postsynaptic potential (Pfeiffer 1966;Bourk 1976; but see Kopp-Scheinpflug et al 2002). Bushy-cell synapses are altered in morphology following cochlear damage (Ryugo et al 1997;Redd et al 2000), but the implications for synaptic transmission of these morphological changes are not clear.…”

“…Adding to this paradoxical situation is the hyperactivity seen in central auditory neurons after SNHL, which is characterized by an abnormally rapid increase of response with stimulus intensity or by a heightened maximum response or both (e.g., Langers et al 2007). This central hyperactivity qualitatively resembles loudness recruitment and thus is a potential neural correlate.…”

Postsynaptic Targets of Type II Auditory Nerve Fibers in the Cochlear Nucleus.

“…1) and terminate in the cochlear nucleus (Lorente de No 1933;Fekete et al 1984;Brown et al 1988a). Type I fibers have an excitatory influence on their postsynaptic targets, leading to discharge of cochlear-nucleus neurons (Pfeiffer 1966;Golding et al 1995;Kopp-Scheinpflug et al 2002). Type I targets in the cochlear nucleus are a variety of types of neurons (Brawer and Morest 1975;Rouiller et al 1986), which have been classified by their morphology using different stains (Osen 1969;Brawer et al 1974).…”