The plasticity-stability balance of auditory cortex synapses: role of sensory experience and synaptic mechanisms

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The brains of many animals (including humans) are highly immature and plastic at birth. This characteristic allows the developing nervous system to be shaped by, and optimally adapt to the specific sensory environment experienced during postnatal life. Over the course of development and aging, plasticity generally declines, resulting in more stable neural connections. However, this transition from brain "plasticity" to "stability" is guided, at least in part, by appropriate sensory (e.g., visual, tactile, auditory) stimulation. For example, the auditory cortex, responsible for processing complex acoustic information, shows a form of development arrest, characterized by the maintenance of high levels of juvenile-like plasticity into adulthood, if sound input is absent or distorted during early postnatal life. My research program is aimed at characterizing the precise role of sensory stimuli in guiding synaptic maturation, as well as providing a detailed analysis of the synaptic and neurochemical mechanisms that mediate the effect of experience on brain development. Three lines of investigation are proposed: Objective #1: Determine the precise role of different sound features (in particular loudness/amplitude, pitch/frequency, and temporal patterns) in driving maturation of auditory cortex synapses. Objective #2: Identify the role of insufficient neurochemical inhibition in the developmental arrest following lack of proper sound exposure during early postnatal life. Objective #3: Characterize neurochemical mechanisms involved in plasticity "gating" in the mature auditory cortex. These objectives are achieved by precise manipulations of the acoustic environment during postnatal development, combined with electrophysiological and pharmacological techniques to determine the developmental (plasticity) state of the auditory cortex. Each objective will create training positions for highly qualified personnel at both the graduate and undergraduate level, leading to the mastery of advanced, state-of-the-art technical and professional skills. Together, this work will lead to significant advances in our understanding of postnatal auditory cortex maturation and of general principles governing sensory-driven development of complex, mammalian brains.