Regulating synaptic strength during development

Dan Sanes

Abstract

The functional properties of central synapses can change rapidly with use, particularly during development. To address this issue, we have studied excitatory and inhibitory synaptic transmission in the auditory brainstem of control and deafened gerbils. Animals are surgically deafened just prior to the onset of hearing, and permitted to survive for 1-14 days. A brain slice preparation of the inferior colliculus (IC) which includes the ascending afferents is produced, and whole-cell recordings are obtained. Following bilateral hearing loss, afferent-evoked inhibitory synaptic currents decline dramatically in the IC, while evoked excitatory synaptic currents become larger. The decreased inhibitory drive is due, in part, to the diminished function of the potassium-dependent chloride cotransporter, and a depolarization of the IPSC reversal potential. The increased excitatory drive is due, in part, to an increase in functional NMDA receptors. These changes to synaptic physiology can be observed within 24 hours of deafening. Our recent findings suggest that deafness leads to similar changes in AI. Whole-cell recordings from layer 2/3 pyramidal neurons demonstrate that intracortically-evoked IPSPs decline in amplitude, while thalamus-evoked EPSPs become longer in duration. In summary, deafness alters the balance between excitatory and inhibitory synaptic strength in both the auditory midbrain, and we are currently testing how this concept applies to the cortex. If proper activity is not restored early in development, the persistent excitability may limit the finer integrative computations performed at all levels of the auditory system.

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