How does auditory experience shape neural sensitivity to acoustic events? Non-invasive investigations in animal models.

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The ability to detect and respond quickly to changes in the environment, for example, the appearance, disappearance or movement of an object, impacts significantly on survival. Detecting changes in the acoustic environment is critical to this process; we often rely on our hearing in the dark or in visually-cluttered environments, and for events that occur beyond the field of vision. Because detecting acoustic changes is such a basic and vital ability, and since modern environments are characterized by 'noise pollution' or competing sources of acoustic information - the need to detect important events within a mixture of sounds, is increasingly important. The present proposal seeks to understand how the auditory brain's sensitivity to the unfolding acoustic environment is shaped by previous long-term exposure changes, and the degree to which this sensitivity is mutable during adulthood. Inherent difficulties in assessing the nature of brain mechanisms underlying sensitivity to acoustic changes means that the questions posed in the current proposal have never been, to the best of our knowledge, addressed experimentally. One reason for this deficit lies in the need to control carefully developmental experience and exposure to sound patterns, a requirement that renders investigations in human subjects almost impossible. So too, addressing such questions in animal models is limited by the difficulties that arise in evaluating the results of exposure/training, coupled with a lack of basic knowledge concerning the sites (i.e. which brain areas) to which electrophysiological recordings might be directed (or indeed how detecting acoustic changes relates to activity at the level of single neurons). Here, we propose a method of assessing the long term plasticity of mechanisms underlying detection of acoustic changes by means of non-invasive, gross brain activity - measurements in animal models (mice and guinea pigs), for which behavioral relevance and developmental experience can be carefully controlled. To measure gross brain activity we will employ a small animal MEG (magneto-encephalography) device. Relative to other means of measuring brain responses from small animals, such as EEG (electro-encephalography), this emerging technology is entirely non-invasive, increasing the efficiency of measuring event-related responses, and facilitating repeated measurements from individual animals. In the first experiment proposed, we will examine the effects of training in adulthood on subsequent neural sensitivity to change. Two groups of animals will be exposed to an identical auditory stimulus, containing changes in two sound features (pitch and timbre). One group will be trained to respond to pitch changes, while ignoring timbre changes, and vice versa for the other group. A control group will be exposed to the same stimuli but without a training element. Change-evoked brain responses (measured using MEG) will then be recorded from non-behaving anesthetized animals to determine whether, and in which manner, such training alters change-detection mechanisms in auditory cortex, A second experiment will investigate the extent to which passive exposure to sound during development, shapes neural representations of change detection in adulthood. Different groups of animals will be raised in specifically controlled sound environments such that the statistics of sound features across groups will be identical, but the statistics of changes (the frequency of changes encountered) different. Following exposure, MEG responses to acoustic changes will be measured. Differences in response patterns between groups will be specifically attributable to the differential exposure of the groups to patterns of changes. The outcome of this experiment will reveal the means by which statistics of acoustic changes shape cortical responses, and which changes (rare or commonly-occurring) are dominant in this process.