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UBC Theses and Dissertations

Orexin modulation of ventral tegmental area dopamine neurons Baimel, Corey


Dopamine neurons in the ventral tegmental area (VTA) are critically involved in the expression of motivated behaviour. The activity of dopamine neurons is regulated by intrinsic conductances and by synaptic inputs, both of which are subject to neuromodulatory influences. This thesis explores how orexin signalling alters the synaptic regulation and the activity of VTA dopamine neurons. Chapter 1 describes a role for dopamine in motivated behaviour and highlights how drugs of abuse alter synaptic transmission in the mesocorticolimbic dopamine system to drive compulsive reward seeking. Moreover, it outlines how lateral hypothalamic orexin projections to the VTA alter synaptic transmission onto dopamine neurons to promote motivated behaviour. Chapter 2 examines how orexin signalling gates morphine-induced synaptic plasticity in the VTA. We demonstrate that inhibiting orexin receptor signalling in the VTA blocks morphine-induced increases and decreases in the strength of excitatory and inhibitory synaptic transmission respectively. Orexin neurons coexpress the inhibitory peptide dynorphin and the two are likely coreleased. In chapter 3 we demonstrate that orexin and dynorphin modulate the activity of dopamine neurons in a projection-target specific manner. Orexin preferentially increased the output of dopamine neurons that project to the lateral shell of the nucleus accumbens (NAc), while dynorphin was more effective at inhibiting the activity of dopamine neurons that project to the basolateral amygdala (BLA). Chapter 4 discusses the strength and weaknesses of these experiments and proposes future research to further enhance our understanding of orexin modulation of VTA dopamine neurons.

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