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Paraventricular Hypothalamic Nucleus Pathways to Cardiac Vagal Neurons Open Access

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Paraventricular Hypothalamic Nucleus Pathways to Cardiac vagal NeuronsThe paraventricular nucleus of the hypothalamus (PVN) plays an important role in controlling cardiovascular function both via release of hormones from the pituitary and additionally via its descending pathways to the brainstem and spinal cord. Neuroanatomical studies suggest that PVN neurons project to cardiac vagal neurons (CVNs) that are essential in parasympathetic control of the heart in the nucleus ambiguus and dorsal motor nucleus of the vagus. I performed a comprehensive evaluation of different methods to selectively evoke transmitter release from distant synapses using optogenetic approaches, comparing different lentiviral vectors, with sub-population-specific and strong promoters, and transgenic methods to express and photostimulate Channelrhodopsin-2 (ChR2) in the long-range projections of the PVN neurons to brain stem (CVNs). I demonstrated that a monosynaptic PVN pathway innervates CVNs through glutamatergic projections, using a VSVg pseudotyped lentiviral vector with a strong neuronal promoter (human synapsin1 fragment) to drive ChR2-EYFP expression in PVN neurons. I found evidence for a facilitative role of oxytocin (OXT) in this pathway, since OXT antagonists abolished the facilitation. These findings suggest that OXT released from PVN terminals selectively facilitates glutamatergic neurotransmission from PVN to CVNs. Our data support that endogenous released OXT mediates facilitation of glutamatergic innervation of CVNs, delineating a role for OXT to increase parasympathetic cardiac activity.

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