Development of gerbil medial superior olive: integration of temporally delayed excitation and inhibition at physiological temperature

Abstract

The sensitivity of medial superior olive (MSO) neurons to tens of microsecond differences in interaural temporal delay (ITD) derives in part from their membrane electrical characteristics, kinetics and timing of excitatory and inhibitory inputs, and dendrite structure. However, maturation of these physiological and structural characteristics are little studied, especially in relationship to the onset of auditory experience. We showed, using brain slices at physiological temperature, that MSO neurons exhibited sensitivity to simulated temporally delayed (TD) EPSCs (simEPSC), injected through the recording electrode, by the initial phase of hearing onset at P10, and TD sensitivity was reduced by block of low threshold potassium channels. The spike generation mechanism matured between P10 and P16 to support TD sensitivity to adult-like excitatory stimuli (1-4 ms duration) by P14. IPSP duration was shorter at physiological temperature than reported for lower temperatures, was longer than EPSP duration at young ages, but approached the duration of EPSPs by P16, when hearing thresholds neared maturity. Dendrite branching became less complex over a more restricted time frame between P10 and P12. Because many physiological and structural properties approximated mature values between P14 and P16, we studied temporal integration of simEPSCs and IPSPs at P15. Only a narrow range of relative onset times (< 1 ms) yielded responses showing sensitivity to TD. We propose that shaping of excitatory circuitry to mediate TD sensitivity can begin before airborne sound is detectable, and that inhibitory inputs having suboptimal neural delays may then be pruned by cellular mechanisms activated by sensitivity to ITD.

Medial Superior Olivary Neurons Receive Surprisingly Few Excitatory and Inhibitory Inputs with Balanced Strength and Short-Term Dynamics

“…The AP current threshold obtained from the experiments described above (Fig. 4) is more than twofold larger than previous reports have indicated (Scott et al, 2005;Chirila et al, 2007). In these earlier reports the current threshold was estimated from long step depolarizations, whereas the current thresholds derived from our experiments are based on EPSCs with extremely fast time courses (Fig.…”

“…Our estimates therefore represent a lower bound for the number of excitatory fibers required for AP generation. The corresponding synaptic currents that are required for AP generation were found to be larger than previously estimated (Scott et al, 2005;Chirila et al, 2007). However, the estimate was confirmed by recording voltage responses elicited by finely graded simulated EPSCs with fast time courses that mimic the actual EPSC waveforms generated in the MSO.…”

“…The electrophysiological properties of MSO neurons and the time course of their inputs are developmentally regulated and a dependency on the recording temperature has been reported Magnusson et al, 2005;Scott et al, 2005;Chirila et al, 2007). To obtain quantitative estimates comparable to the function described by in vivo physiology, we restricted our in vitro circuit analysis to acute horizontal brain slices (90 -120 m thickness) from adult [postnatal day (P) 60 -100] Mongolian gerbils.…”

“…Neurons in the MSO have a low input resistance (Magnusson et al, 2005;Scott et al, 2005;Chirila et al, 2007), suggesting that large synaptic currents are required for action potential (AP) generation and for inhibitory inputs to have a significant impact. This assumption is supported by ultrastructural evidence for multiple active zones on both excitatory and inhibitory synaptic boutons contacting the MSO (Clark, 1969;Lindsey, 1975;Kiss and Majorossy, 1983;Brunso-Bechtold et al, 1990;Kapfer et al, 2002).…”

The volley theory and the spherical cell puzzle

“…Their primary termination sites appear to be on cells in brainstem nuclei that provide inhibitory inputs to other regions. These include the large calyx of Held terminals onto glycinergic cells of the contralateral medial nucleus of the trapezoid body (MNTB) that provide inhibitory inputs to LSO and MSO cells (Glendenning et al, 1985, Kuwabara et al, 1991, Banks and Smith, 1992, Cant and Hyson, 1992, Smith et al, 1998, Chirila et al, 2007 (Kopp-Scheinpflug et al, 2008, this issue), terminals onto neurons of the ipsilateral lateral nucleus of the TB that provide inhibitory inputs to MSO cells (e.g. Cant and Hyson, 1992, Spirou and Berrebi, 1997, Spirou et al, 1998; and a contralateral projection to superior paraolivary nucleus or dorsomedial periolivary nucleus that sends a GABAergic projection to the inferior colliculus (e.g.…”