Interval-counting neurons in the anuran auditory midbrain: factors underlying diversity of interval tuning.

In anurans, the temporal patterning of sound pulses is the primary information used for differentiating between spectrally similar calls. One class of midbrain neurons, referred to as 'interval-counting' cells, appears to be particularly important for discriminating among calls that differ in pulse repetition rate (PRR). These cells only respond after several pulses are presented with appropriate interpulse intervals. Here we show that the range of selectivity and sharpness of interval tuning vary considerably across neurons. Whole-cell recordings revealed that neurons showing temporally summating excitatory postsynaptic potentials (EPSPs) with little or no inhibition or activity-dependent enhancement of excitation exhibited low-pass or band-pass tuning to slow PRRs. Neurons that showed inhibition and rate-dependent enhancement of excitation, however, were band-pass or high-pass to intermediate or fast PRRs. Surprisingly, across cells, interval tuning based on membrane depolarization and spike rate measures were not significantly correlated. Neurons that lacked inhibition showed the greatest disparities between these two measures of interval tuning. Cells that showed broad membrane potential-based tuning, for example, varied considerably in their spike rate-based tuning; narrow spike rate-based tuning resulted from 'thresholding' processes, whereby only the largest depolarizations triggered spikes. The potential constraints associated with generating interval tuning in this manner are discussed.

Mechanisms of long-interval selectivity in midbrain auditory neurons: roles of excitation, inhibition, and plasticity.

Stereotyped intervals between successive sound pulses characterize the acoustic signals of anurans and other organisms and provide critical information to receivers. One class of midbrain neuron responds selectively when pulses are repeated at slow rates (long intervals). To examine the mechanisms that underlie long-interval selectivity, we made whole cell recordings, in vivo, from neurons in the anuran inferior colliculus (anuran IC). In most cases, long-pass interval selectivity appeared to arise from interplay between excitation and inhibition; in approximately 25% of these cases, the delayed inhibition to a pulse overlapped with the excitation to the following pulse at fast pulse repetition rates (PRRs), resulting in a phasic "onset" response. In the remaining cases, inhibition appeared to precede excitation. These neurons did not respond to fast PRRs apparently because delayed excitation to a pulse overlapped with the inhibition to the following pulse. These results suggest that the relative timing of inhibition and excitation govern differences in the response properties of these two cell types. Loading cells with cesium increased their responses to fast AM rates, supporting a role for inhibition in long-interval selectivity. Three cells showed little or no evidence of inhibition and exhibited strong depression of excitation. These findings are discussed in the context of current models for long-pass interval selectivity.

Midbrain auditory neurons integrate excitation and inhibition to generate duration selectivity: an in vivo whole-cell patch study in anurans.

Sound duration can play a pivotal role in the reproductive behavior of anuran amphibians. Here, we report the first whole-cell recordings from duration-selective neurons in the anuran torus semicircularis, in vivo. We show that most short-pass duration-selective cells exhibited short-latency inhibition and delayed excitation. The duration of the inhibition increased with tone burst duration. Hence, for long-duration tone bursts, inhibition overlapped with excitation, reducing or eliminating spikes; no postinhibitory rebound was present. Other short-pass cells, however, showed inhibition only for long-duration tone bursts. Bandpass duration selectivity also involved interplay between inhibition and excitation; inhibition negated excitation with tone bursts that exceeded the optimum duration. Additionally, however, bandpass selectivity arose from stimulus-dependent excitation; tone bursts of sufficiently long duration were required to elicit excitation. Similarly, long-pass neurons showed inhibition and duration-dependent enhancement of excitation; long-pass selectivity resulted from enhanced excitation outlasting the transient inhibition or, in some cases, excitation overriding concurrent inhibition. Last, we evaluated the stimulus specificity of duration-selective neurons to variations in pulse repetition rate. We show that (1) most neurons that exhibited long-pass selectivity for tone-burst duration nonetheless responded to short-duration pulses when repeated at particular rates, and (2) some neurons that showed selectivity for tone burst duration also showed selectivity for pulse train duration. These novel response profiles appear to result from interplay between inhibition and time- and activity-dependent changes in excitation strength. These findings are discussed in the context of prevailing models of duration selectivity and acoustic communication in anurans.

Counting on inhibition and rate-dependent excitation in the auditory system.

The intervals between acoustic elements are important in audition. Although neurons have been recorded that show interval tuning, the underlying mechanisms are unclear. The anuran auditory system is well suited for addressing this problem. One class of midbrain neurons in anurans responds selectively over a narrow range of pulse-repetition rates (PRRs) and only after several sound pulses have occurred with the "correct" timing. This "interval-counting" process can be reset by a single incorrect interval. Here we show, from whole-cell patch recordings of midbrain neurons in vivo, that these computations result from interplay between inhibition and rate-dependent excitation. An individual pulse or slowly repeated pulses elicited inhibition and subthreshold excitation. Excitation was markedly enhanced, however, when PRR was increased over a neuron-specific range. Spikes were produced when the enhanced excitation overcame the inhibition. Interval-number thresholds were positively correlated with the strength of inhibition and number of intervals required to augment the excitation. Accordingly, interval-number thresholds decreased when inhibition was attenuated by loading cells with cesium fluoride. The selectivity of these neurons for the interpulse interval, and therefore PRR, was related to the time course of excitatory events and the rate dependence of enhancement; for cells that were tuned to longer intervals, EPSPs were broader, and enhancement occurred at slower PRRs. The frequency tuning of the inhibition generally spanned that of the excitation, consistent with its role in temporal computation. These findings provide the first mechanistic understanding of interval selectivity and counting in the nervous system.

Pulse rise time but not duty cycle affects the temporal selectivity of neurons in the anuran midbrain that prefer slow AM rates.

Recovery-type auditory neurons in the anuran inferior colliculus (IC) respond with band-pass or low-pass selectivity for sinusoidal AM. These cells respond to each modulation cycle at slow AM rates and respond only at the onset of fast AM or pulse repetition rate (PRR) stimuli, failing to recover from the effects of early pulses. This selectivity is not altered by changes in pulse duty cycle. The recovery process is governed therefore by the interpulse interval and not the dimension of the gap between sound pulses. Most of these neurons preferred fast rise times, which is characteristic of the sound pulses in the calls of Hyla regilla and Rana pipiens, the two species selected for this study.

Auditory midbrain neurons that count.

Many acoustic communication signals, including human speech and music, consist of a precise temporal arrangement of discrete elements, but it is unclear whether this precise temporal patterning is required to activate the sensory neurons that mediate signal recognition. In a variety of systems, neurons respond selectively when two or more sound elements are presented in a particular temporal order and the precise relative timing of these elements is particularly important for 'delay-tuned' neurons, including 'tracking' types, in bats. Here we show that one class of auditory neurons in the midbrain of anurans (frogs and toads) responds only to a series of specific interpulse intervals (IPIs); in the most selective cases, a single interval that is slightly longer or shorter than the requisite interval can reset this interval-counting process.