Mechanisms of inhibition and neuronal integration for signal processing in the primary auditory cortex of the Mongolian gerbil (Meriones unguiculatus)
A. A fundamental property of hearing is the decomposition of complex sounds into perceptually distinct frequency components. Each receptor cell in the cochlea and most centrally located neurons respond only to a limited range of frequencies. The individual frequency channels are spatially organized on the cortical surface. This consistent topographical pattern provides a framework for the investigation of other functional organization principles, e.g., the functional properties of neurons in the six cortical layers and the responsiveness of neurons to complex sounds. The frequency specific features of inhibition should play an important role in shaping a neuron’s response to complex behaviorally relevant stimuli. Physiological and immunocytochemical evidence indicates a layer-dependent organization of inhibitory circuits in the neocortex. To investigate the contribution of GABAergic inhibition to frequency tuning in the different cortical layers, single and multi units were recorded in near-radial penetrations before and during iontophoretic application of the GABAA-receptor antagonist bicuculline in the auditory cortex of the lightly anaesthetized gerbil (Meriones unguiculatus). Bicuculline generally increased the spontaneous neuronal activity and enhanced and prolonged onset responses to sound. Application of bicuculline often resulted in a shift of the most sensitive frequency of the neurons’ receptive fields and a decrease of threshold (5.5 dB). A broadening of the frequency tuning evident by lower Q40dB values was observed in 63% of the units. In units with several peaks in their tuning curve or clearly separated response areas, bicuculline application removed inhibitory gaps in the receptive fields and created single-peaked tuning curves. The influence of bicuculline on the receptive field size was not significantly layer-specific but tended to be most pronounced in layers V and VI. In layer VI, "silent" neurons were frequently found that responded to sound only when GABAergic inhibition was antagonized. From the analysis of postembedding GABA immunocytochemistry, the proportion of GABAergic neurons was found to be maximal in layers I and V, and the number of GABAergic perisomatic puncta (axon terminals) on cell somata peaked in layer V. The influence of bicuculline was compared with the effects of two-tone suppression. It was found that in some units, the effects of suppression could be partially mediated by intracortical GABAergic inhibition. In some units in layers IV, V, and VI, additionally to the initial excitatory activity in response to stimulus onset, a second, long-lasting excitatory response occurred several hundred milliseconds after the stimulus. This late response was not dependent on stimulus duration and could be enhanced or elicited by GABAA blockade. The fact that several, rhythmically occurring late responses were elicited by the application of bicuculline suggests that recurrent excitatory networks can become entrained by small modifications of inhibition. B. In the natural environment, acoustic signals like animals’ communication sound or human speech is often masked by background noise. Amplitude fluctuations are often superimposed upon environmental sounds on their path of transmission which can lead to a distinct temporal structure of the sound. Furthermore, many natural background sounds are often temporally structured. Vertebrates have evolved mechanisms to exploit amplitude modulations in background noise to improve signal detection. Psychophysical and behavioral experiments have shown that amplitude-modulated background noise (comodulated noise) is less effective as a masker than unmodulated noise bands of the same bandwidth, a phenomenon called comodulation masking release (CMR). This phenomenon has been extensively studied in human psychoacoustics. However, the underlying neural mechanisms are still debated. Animal models in which a direct comparison of the neuronal response and the behaviorally measured performance is possible could increase our understanding of the underlying mechanisms. CMR could be demonstrated behaviorally and neurophysiologically in a songbird, however, models for mammals are still lacking. In behavioral experiments, Kittel et al. (2000) demonstrated CMR in the gerbil. In the present study, using acoustic stimuli that were identical with those of a behavioral experiment, a neural correlate of CMR was described in the auditory cortex of the gerbil and compared with the behavioral data. In this study of neural mechanisms of masking release in the primary auditory cortex of the anaesthetized gerbil, I determined neural detection thresholds for 200-ms test tones presented in a background of band-pass amplitude modulated (50 Hz) noise maskers of different bandwidth (between 50 and 3200 Hz). Neural release from masking caused by comodulated band-pass noise was evident at the level of the gerbil’s primary auditory cortex. On average, the largest masking release (median 6.9 dB) was found for a masker bandwidth of 3200 Hz. This is less than the median masking release of 15.7 dB observed in the behavioral study in the gerbil. For most masker bandwidths, however, a small fraction of the neurons exhibited a masking release that was close to or even larger than the behavioral masking release. The observation that the release from masking increased as a function of the masker bandwidth indicates that spectral components remote from the signal frequency enhance the signal detection. However, there was no correlation between the neurons’ filter bandwidths and the amount of masking release. Thus, neuronal masking release in the gerbil primary auditory cortex could be attributed to both signalmasker interactions across different frequency channels and also to mechanisms that act within a single frequency channel. The gerbil appears to be a suitable animal model for additional studies comparing behavioral and physiological performance in the same species. These studies could increase our understanding of the perceptual mechanisms that are useful for the analysis of auditory scenes.
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