The contribution of zincergic neurons to cerebral cortical plasticity

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All of the research in my laboratory, since its inception, has been directed toward gaining a better understanding of the intrinsic mechanisms that mediate and facilitate the remarkable malleability that is characteristic of the mammalian cerebral cortex. My perspective in the past was largely guided by studies of the postnatal development of cortex, as it is during this time that the neocortex is most plastic. It is our belief that the cellular and molecular mechanisms that underlie this plasticity are likely the same as are present in later development, and in old age, those that mediate processes such as learning and memory, and recovery from injury. The anatomical, molecular, physiological, and behavioural substrates that underlie the ability of neurons and neuronal networks in the cerebral cortex to alter their organization in response to changing sensory environments are largely unknown. However, it is known that neuronal activity profoundly affects the establishment and maintenance of neuronal circuits throughout the brain. In the most recent NSERC-funded granting period we have established abundant lines of evidence that implicate neurons that contain zinc in synaptic vesicles (are zincergic), and modulate the release of zinc in an activity- and experience-dependent manner, might play a special role in mediating synaptic plasticity within cerebral cortical circuits. Across this period of time we have also acquired a number of technologies that will allow us to better understand the specific role of zincergic neurons and synaptic zinc in mediating cerebral cortical plasticity. The tools include specific transgenic and knockout mice with altered expression of zinc signaling pathways, as well as the development of anatomical, molecular and physiological techniques and probes that allow us to monitor the activation zincergic signaling pathways. Using these novel tools, together with traditional physiological, anatomical, molecular and behavioural methodologies, we intend to continue our studies in rodent models to establish the role of zincergic neurons, and zinc itself, in the normal functioning and synaptic plasticity of cerebral cortical circuits.