Multi-electrode Recording Analysis in the Rat Auditory Brainstem suggests that the Developmental Increase in Spontaneous Neuronal Activity before Hearing Onset is Mediated by Co-activation of Local Clusters.

PAN G, DI GUILMI MN, RAVI K, BABOU C AND RODRÍGUEZ-CONTRERAS A

Congreso; 41th ARO Midwinter Meeting of ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY; 2018

ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY

Before the onset of hearing around postnatal day 12 (P12), auditory neurons in the medial nucleus of the trapezoid body (MNTB) and the inferior colliculus (IC) of rats fire spontaneous bursts of action potentials that originate in the inner ear (Tritsch et al. 2010. Nature Neurosci. 13:1050-1052). To fully understand the significance of spontaneous burst firing for the development of the central auditory system requires knowledge of the activity patterns in populations of auditory neurons, including how patterns of activity are affected by anesthesia, and eventually how experimental manipulations of activity during the prehearing stage affect hearing development in the short and the long term. In this study we recorded extracellular action potentials with multi-electrode arrays placed in the MNTB of Wistar rat pups anesthetized with isoflurane or ketamine/xylazine mix (n=30 pups). Electrophysiology recordings showed that multi-unit activity increased during postnatal development, being detected as early as P3 in ketamine/xylazine anesthetized pups (multi-unit range 0-10 spikes/s), but with a marked increase at P6 in both, isoflurane (multi-unit range 0-15 spikes/s) and ketamine/xylazine (multi-unit range 0-30 spikes/s) conditions. Cross correlation analysis of multi-unit activity simultaneously recorded across 16 recording sites at P9 revealed a moderate relationship between Pearson?s correlation coefficient and distance, with correlation coefficient values >0.6 observed predominately at distances of 50 m and 100 m (pairwise comparison range 50-450 m; spike detection threshold 7 standard deviations above the mean; n=4 pups). Furthermore, spike sorting of multi-unit activity confirmed individual unit spike trains with inter-spike interval histograms that are consistent with burst firing described in previously published single-cell recordings. These preliminary results suggest that local activation of neuronal clusters is a predominant pattern of ensemble activity in the MNTB before hearing onset and that either changes in the number of neurons per cluster, the number of co-active clusters or both, can explain the increase in action potential firing recorded with multi-electrode arrays. Ongoing studies are focused in cross correlation analysis of simultaneously recorded individual spike trains, the cellular mechanisms that generate co-active clusters, and how anesthesia affects burst firing and multi-unit activity levels in awake animals.