The development of synaptic function and integration in the central auditory system.

Abstract

The development of inhibitory synaptic transmission is difficult to assess because the afferents usually arise from intrinsic neurons that are difficult to stimulate independently. The postnatal maturation of excitatory and inhibitory synaptic function was compared in the gerbil lateral superior olive (LSO), where it is possible to stimulate physically discrete afferent projections. Intracellular recordings obtained in a brain slice preparation revealed that transmission was prominent at birth. The EPSPs and IPSPs were up to 2 orders of magnitude longer than in more mature animals. Brief trains of electrical stimulus pulses led to a temporal summation of postsynaptic potentials (PSPs) in 1-14 d animals resulting in prolonged depolarizations or hyperpolarizations. In neonates, the depolarization could exceed 1 sec following a 70 msec stimulus train. The IPSPs in neonates were often of sufficient amplitude to evoke a rebound depolarization or action potential. The number of converging afferents was estimated from the quantized increases in PSP size. There was a significant decrease with age, suggesting that both inhibitory and excitatory afferents were eliminated during the first 3 postnatal weeks. The integration of action potentials with IPSPs was examined with conjoint stimuli to the two afferent pathways, and demonstrated that the effective IPSP duration decreased approximately 20-fold during the first 3 postnatal weeks. The magnitudes and durations of electrical stimulus-evoked PSPs suggest that spontaneous discharge of afferents to the LSO could have a substantial impact on their development, even prior to the response to airborne sound at 12 d. Furthermore, the synaptic responses obtained at 12-14 d postnatal indicated that both amplitude and temporal processing remain compromised. These immature synaptic properties would be expected to compound the inadequacies present in the cochlea and cochlear nucleus.