Balance or imbalance: inhibitory circuits for direction selectivity in the auditory system.

The auditory system detects and processes dynamic sound information transmitted in the environment. Other than the basic acoustic parameters, such as frequency, amplitude and phase, the time-varying changes of these parameters must also be encoded in our brain. Frequency-modulated (FM) sound is socially and environmentally significant, and the direction of FM sweeps is essential for animal communication and human speech. Many auditory neurons selectively respond to the directional change of such FM signals. In the past half century, our knowledge of auditory representation and processing has been updated frequently, due to technological advancement. Recently, in vivo whole-cell voltage clamp recordings have been applied to different brain regions in sensory systems. These recordings illustrate the synaptic mechanisms underlying basic sensory information processing and provide profound insights toward our understanding of neural circuits for complex signal analysis. In this review, we summarize the major findings of direction selectivity at several key auditory regions and emphasize on the recent discoveries on the synaptic mechanisms for direction selectivity in the auditory system. We conclude this review by describing promising technical developments in dissecting neural circuits and future directions in the study of complex sound analysis.

A computational model of inferior colliculus responses to amplitude modulated sounds in young and aged rats.

The inferior colliculus (IC) receives ascending excitatory and inhibitory inputs from multiple sources, but how these auditory inputs converge to generate IC spike patterns is poorly understood. Simulating patterns of in vivo spike train data from cellular and synaptic models creates a powerful framework to identify factors that contribute to changes in IC responses, such as those resulting in age-related loss of temporal processing. A conductance-based single neuron IC model was constructed, and its responses were compared to those observed during in vivo IC recordings in rats. IC spike patterns were evoked using amplitude-modulated tone or noise carriers at 20-40 dB above threshold and were classified as low-pass, band-pass, band-reject, all-pass, or complex based on their rate modulation transfer function tuning shape. Their temporal modulation transfer functions were also measured. These spike patterns provided experimental measures of rate, vector strength, and firing pattern for comparison with model outputs. Patterns of excitatory and inhibitory synaptic convergence to IC neurons were based on anatomical studies and generalized input tuning for modulation frequency. Responses of modeled ascending inputs were derived from experimental data from previous studies. Adapting and sustained IC intrinsic models were created, with adaptation created via calcium-activated potassium currents. Short-term synaptic plasticity was incorporated into the model in the form of synaptic depression, which was shown to have a substantial effect on the magnitude and time course of the IC response. The most commonly observed IC response sub-types were recreated and enabled dissociation of inherited response properties from those that were generated in IC. Furthermore, the model was used to make predictions about the consequences of reduction in inhibition for age-related loss of temporal processing due to a reduction in GABA seen anatomically with age.

A computational model of cellular mechanisms of temporal coding in the medial geniculate body (MGB).

Acoustic stimuli are often represented in the early auditory pathway as patterns of neural activity synchronized to time-varying features. This phase-locking predominates until the level of the medial geniculate body (MGB), where previous studies have identified two main, largely segregated response types: Stimulus-synchronized responses faithfully preserve the temporal coding from its afferent inputs, and Non-synchronized responses, which are not phase locked to the inputs, represent changes in temporal modulation by a rate code. The cellular mechanisms underlying this transformation from phase-locked to rate code are not well understood. We use a computational model of a MGB thalamocortical neuron to test the hypothesis that these response classes arise from inferior colliculus (IC) excitatory afferents with divergent properties similar to those observed in brain slice studies. Large-conductance inputs exhibiting synaptic depression preserved input synchrony as short as 12.5 ms interclick intervals, while maintaining low firing rates and low-pass filtering responses. By contrast, small-conductance inputs with Mixed plasticity (depression of AMPA-receptor component and facilitation of NMDA-receptor component) desynchronized afferent inputs, generated a click-rate dependent increase in firing rate, and high-pass filtered the inputs. Synaptic inputs with facilitation often permitted band-pass synchrony along with band-pass rate tuning. These responses could be tuned by changes in membrane potential, strength of the NMDA component, and characteristics of synaptic plasticity. These results demonstrate how the same synchronized input spike trains from the inferior colliculus can be transformed into different representations of temporal modulation by divergent synaptic properties.