While the development of excitatory responses has been the focus of considerable research, the ontogeny of inhibitory connections has received relatively little attention. The lateral superior olive (LSO), an auditory nucleus in the ventral brain stem, is a favorable system in which to compare the maturation of an inhibitory and an excitatory input. Neurons in the LSO are excited by stimuli delivered to the ipsilateral ear and inhibited by similar stimuli to the contralateral ear. Single-neuron recordings were made to characterize tone-evoked responses at the onset of hearing and in adult Mongolian gerbils. The results indicated that frequency selectivity was significantly poorer in young than adult animals. In several cases, neurons within the same animal were found to have disparate tuning properties, such that one of the units had "adult-like" tuning, while the other was much more broadly tuned. No difference existed between excitatory and inhibitory tuning within any age group. The degree to which the excitatory and inhibitory characteristic frequencies of an LSO neuron were correlated was used as a measure of tonotopic map alignment. A significant improvement of matching was seen with increasing age. A comparison of excitatory and inhibitory thresholds indicated that the inhibitory system was relatively more efficacious in young than adult animals. The ability of LSO neurons to respond to interaural intensity differences, the binaural parameter to which they are sensitive, indicated 3 differences between adult and young animals: the dynamic range was smaller, the slope was shallower, and the sample of neurons encoded a constrained range of interaural intensity difference values. We conclude that the maturation of the inhibitory and excitatory systems are nearly identical.

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.

Neural activity has been implicated as having both a trophic function and a role in synaptic specificity. Sensory deprivation studies in a large number of developing systems have resulted in the pathological morphology of neurons and abnormal response properties. If the relative timing of discharge among afferent terminals is a cue employed by the developing system to refine the array of synaptic connections, then altering the discharge patterns should hinder this process. In the present experiments, we investigate the role played by the temporal pattern of neural activity during the ontogeny of frequency tuning in the mouse central auditory system. Postnatal animals were exposed to acoustic stimuli, repetitive clicks, that continuously entrained a large proportion of primary afferents from the onset of hearing until an age at which tuning curves should have been adult-like. The amount of fatigue to repetitive clicks was characterized at the level of the eighth nerve and inferior colliculus in normal animals. Frequency tuning curves obtained from the inferior colliculus were used as an assay for the specificity of neural connections. Click-reared animals had significantly broader tuning curves than did normally reared mice, particularly for units with best frequencies in the 10- to 15-kHz range. Furthermore, it was found that this change could not be attributed to the selective loss of the sustained component of the response. The affected range is interpreted in terms of the frequency spectrum of the click and the fact that lower frequency regions of the inferior colliculus were found to habituate rapidly. The click-rearing environment did not appear to affect unit spontaneous activity or response latency, nor did it alter the tonotopic map in the inferior colliculus. We argue against the possibility of cochlear damage based on threshold and high frequency cutoff measurements. Mice were reared in a second acoustic environment, repetitive pulses of two added frequencies, as a control for the effects of the click stimulus. This rearing paradigm did not lead to a broadening of tuning curves. It did, however, alter the properties of bimodal tuning curves. For units with bimodal tuning curves having best frequencies in the range of the rearing frequencies, it was found that the second excitatory area had a lower than normal threshold. In addition, the frequency range separating the peaks of the two excitatory regions was statistically smaller. These results are discussed with reference to the specific frequencies used in the rearing paradigm.(ABSTRACT TRUNCATED AT 400 WORDS)

The concentration and relative distribution of glycine receptors were determined for gerbil brain stem auditory nuclei using 3H-strychnine and quantitative autoradiographic techniques. Significant binding was observed in the anteroventral cochlear nucleus, the dorsal cochlear nucleus, the lateral superior olivary nucleus, and the inferior colliculus. A non-uniform distribution of binding was seen in 3 of these nuclei, such that the greatest concentration of glycine receptors was located in the high-frequency regions. An analysis of neuron soma density suggested that the amount of post-synaptic membrane could partially explain the distribution of receptor.

The concentration and relative distribution of glycine receptors were determined for the gerbil lateral superior olive at several postnatal ages. Quantitative autoradiographic techniques revealed significant 3H- strychnine binding to all regions of the nucleus from 4 to 90 d. However, during the first 20 d, a nonuniform distribution of binding emerged, such that the greatest concentration of receptor was found in the high-frequency region of the nucleus. An analysis of neuron packing density showed an approximate 2-fold distribution along the same axis at all ages. This evidence is consistent with an elimination of glycine receptors in the ventral region of the lateral superior olive as maturation progresses.