Electrophysiological study of dopamine neurons in the dorsal raphe nucleus & ventrolateral periaqueductal grey

Abstract

The midbrain dopamine system plays a fundamental conserved role in regulating behaviour, and its dysfunction is associated with several neuropsychiatric disorders including addiction, schizophrenia, and Parkinson’s Disease. Midbrain dopamine neurons display considerable heterogeneity in their neurochemical, electrophysiological, and functional properties, and project to many cortical and subcortical structures. The majority of these neurons reside within the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA), but a less well-known, and understudied, dopamine population are housed within the dorsal raphe nucleus (DRN) and ventrolateral periaqueductal grey (vlPAG). These neurons provide the majority of the dopaminergic input to the central extended amygdala and have been implicated in the sleep-wake cycle and mediating the effects of opiates. However, their electrophysiological properties have not been examined. I have studied these neurons in mice using immunohistochemistry and electrophysiology in an acute brain slice preparation ex vivo. I found that they display similar properties to some VTA dopamine neurons, and noted co-expression of vasoactive intestinal peptide in a subset of this population. A characteristic feature of VTA dopamine neurons is the potentiation observed at glutamatergic synapses following a single dose of addictive drug or an acute stress experience. I investigated whether DRN/vlPAG dopamine neurons would show cocaine-induced plasticity and found that glutamatergic synapses were potentiated not only by a single dose of cocaine, but also by acute social isolation. This potentiation was associated with a change in AMPAR transmission, which is similar to that observed following cocaine in the VTA. I also investigated the hypothesis that this plasticity is a result of acute anxiety using behavioural analysis and administration of anxiolytic compounds. These findings suggest another form of salient stimulus which can induce plasticity in dopamine neurons, and have relevance to several neuropsychiatric diseases including those modelled by social isolation.