The role of zinc signalling in the amygdala

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We are constantly attributing valence to sensory information that is encountered as we navigate our environment - is it pleasant and rewarding or noxious and aversive? We learn to predict positive and negative outcomes that are tied to those experiences, and make appropriate emotional and behavioural responses, to approach rewards and to escape/avoid danger. This is essential for our survival. One region of the brain, the basolateral complex of the amygdala (BLA), receives dense sensory inputs and is known to be necessary for encoding stimulus valence. Neurons in the BLA send projections to other regions of the brain that are responsible for making appropriate behavioural responses and for forming memories for aversive events and reward associations. My laboratory is interested in understanding the signaling mechanisms whereby valence-specific emotional information is processed and conveyed among these brain regions.     We have discovered that the BLA contains a large number of neurons that uniquely use zinc as a neurotransmitter. We also see that in regions of the brain that are targeted by these neurons, they have very high levels of zinc in their synapses, suggesting that signaling by zinc is important for the normal function of connections made by these neurons. The experiments outlined in this proposal are directed toward assessing whether zinc signaling is critical for processing of emotionally relevant information, in circuits formed by BLA neurons.     We have recently acquired a strain of mouse that has been genetically engineered to allow us to selectively target neurons that use zinc as a neurotransmitter, to label them with a visible marker, increase or decrease their activity using light-activated channels, as well as to eliminate their ability to convey a signal using zinc. We will analyze the behaviour of these mice while manipulating the activity of specific zinc neurons in a circuit-specific manner, at the same time controlling their ability to release zinc, while they are exposed to negative or positive experimental contexts. In this way we will be able to understand how zinc neurons, the circuits they form in the brain, and the zinc signals that they transmit, contribute to the function of the amygdala in processing emotionally relevant information.     I have devoted the majority of my academic life engaged in studies directed to understanding the role of zinc containing neurons, and zinc as a neurotransmitter in the mammalian brain. As one of the world's experts in zinc neurobiology, the acquisition of this revolutionary, genetically-engineered mouse provides me with the means to apply novel, state-of-the-art cellular, physiological, molecular and genetic techniques to developing a greater understanding of the fundamental role of zinc signaling in brain function.