Glutamatergic Calcium Responses in the Developing Lateral Superior Olive: Receptor Types and Their Specific Activation by Synaptic Activity Patterns

Abstract

calcium responses in the developing lateral superior olive: receptor types and their specific activation by synaptic activity patterns. J Neurophysiol 90: 2581-2591, 2003. First published July 9, 2003 10.1152/jn.00238.2003. The lateral superior olive (LSO) is a binaural auditory brain stem nucleus that plays a central role in sound localization. Survival and maturation of developing LSO neurons critically depend on intracellular calcium signaling. Here we investigated the mechanisms by which glutamatergic afferents from the cochlear nucleus increase intracellular calcium concentration in LSO neurons. Using fura-2 calcium imaging in slices prepared from neonatal mice, we found that cochlear nucleus afferents can activate all major classes of ionotropic and metabotropic glutamate receptors, each of which contributes to an increase in intracellular calcium. The specific activation of different glutamate receptor classes was dependent on response amplitudes and afferent stimulus patterns. Lowamplitude responses elicited by single stimuli were entirely mediated by calcium-impermeable AMPA/kainate receptors that activated voltage-gated calcium channels. Larger-amplitude responses elicited by either single stimuli or stimulus trains resulted in additional calcium influx through N-methyl-D-aspartate receptors. Finally, high-frequency stimulation also recruited group I and group II metabotropic glutamate receptors, both of which mobilized intracellular calcium. This calcium release in turn activated a strong influx of extracellular calcium through a membrane calcium channel that is distinct from voltage-gated calcium channels. Together, these results indicate that before hearing onset, distinct patterns of afferent activity generate qualitatively distinct types of calcium responses, which likely serve in guiding different aspects of LSO development. I N T R O D U C T I O NOne of the major functions of the auditory system is to determine the direction of incoming sound. The lateral superior olive (LSO) is the first station in the ascending auditory pathway that processes interaural intensity differences (Boudreau and Tsuchitani 1970;Caird and Klinke 1983; for review, see Oertel 1999). Neurons in this nucleus are excited by sound at the ipsilateral ear and are inhibited by sound at the contralateral ear. Excitation reaches the LSO via a glutamatergic projection from spherical bushy cells in the ipsilateral anteroventral cochlear nucleus (AVCN, reviewed in Thompson and Schofield 2000). Inhibition reaches the LSO via a glycinergic projection from the medial nucleus of the trapezoid body (MNTB). Both excitatory and inhibitory inputs are tonotopically organized and converge on single LSO neurons in a precise frequencyspecific manner (Oertel 1999;Sanes and Rubel 1988).Normal development of the LSO depends on the presence of afferent inputs and synaptic activity (reviewed in Sanes and Friauf 2000). Abolishing the ipsilateral excitatory inputs by cochlea ablation decreases LSO volume and cell number (Moore 1992) and reduces exc...

Retroinhibition of Presynaptic Ca2+Currents by Endocannabinoids Released via Postsynaptic mGluR Activation at a Calyx Synapse

“…Similar desensitization has been described for other group I mGluR-dependent processes (Guatteo et al, 1999;Francesconi and Duvoisin, 2000;Maejima et al, 2001;Dale et al, 2002). Interestingly, neurons in the lateral superior olive (LSO) (an auditory brainstem nucleus) display a DHPG-induced increase in free cytoplasmic calcium ([Ca 2ϩ ] i ) consisting of a peak followed by a plateau reminiscent of the behavior seen in Figure 1 A2 (Ene et al, 2003). On washout of DHPG, both EPSC amplitude and PPR returned to control levels.…”

“…This may suggest that a transient receptor potential (TRP)-like conductance may mediate part of the shift in membrane current during DHPG application because some TRP channels are activated by increases in [Ca 2ϩ ] i levels (Gee et al, 2003). A Ca 2ϩ -permeable TRP channel activated by DHPG may be present in LSO neurons of mice auditory brainstem (Ene et al, 2003).…”

Glutamatergic inputs and glutamate-releasing immature inhibitory inputs activate a shared postsynaptic receptor population in lateral superior olive

“…In rodent auditory brainstem, expression of VGLUT3 allows glutamate release from immature inhibitory terminals during the first postnatal week, and before P9 a majority of LSO principal neurons exhibit a glutamatergic response to stimulation of the MNTB pathway (Gillespie et al, 2005), as well of course to stimulation of the AVCN pathway (Ene et al, 2003). Investigating the possibility of glutamate spillover in the LSO, we found that stimulation of either pathway resulted in the activation of NMDARs serving the opposite pathway.…”

“…NMDARs are present in the AVCN-LSO pathway (Ene et al, 2003), and during the first postnatal week terminals from both the MNTB-LSO and AVCN-LSO pathways release glutamate onto functional postsynaptic GluN2B-containing NMDA receptors (NMDARs) ; . Throughout the nervous system, the GluN2B subunit is expressed at high levels at early ages before replacement by GluN2A (Monyer et al, 1994;Sheng et al, 1994;Stocca and Vicini, 1998) and NMDAR subunit composition may be associated with specific developmental events (Yoshimura et al, 2003;Liu et al, 2004;Philpot et al, 2007;Zhao and Constantine-Paton, 2007).…”

Large Somatic Synapses on Neurons in the Ventral Lateral Lemniscus Work in Pairs

“…This postsynaptic gate can be opened by a predepolarization leading to the inactivation of the A-type current. This mechanism leaves ample room for modulatory actions that lead to prolonged depolarizations of auditory brainstem neurons, such as the activation of metabotropic glutamate (Ene et al, 2003;Chanda and Xu-Friedman, 2011) or purinergic receptors (Milenkovic et al, 2009). Ongoing excitatory input from cells in the octopus cell area, which can fire at high rates (Godfrey et al, 1975;Rhode et al, 1983;Smith et al, 2005), could similarly lead to the inactivation of this A-type current, opening the gate for information transfer.…”