Hypothalamic excitatory input to AT1AR and TH expressing neurons of the nucleus of the solitary tract in mice

Abstract

Autonomic reflexes are modified during development or in response to specific physiological challenges and disease. One modulating region is the hypothalamic paraventricular nucleus (PVN), whose neurons project to the nucleus of the solitary tract (NTS) to modulate viscerosensory input. Yet the neural circuitry by which this is achieved remains ill-defined. Adeno-associated virus was injected into the hypothalamus of TH-GFP or angiotensin type 1A receptor (AT_1AR)-GFP mice to drive channel rhodopsin 2 (ChR2) expression. Whole-cell recordings of NTS neurons in close proximity to labelled hypothalamic efferents were made in horizontal slices of the brainstem, allowing activation of both hypothalamic and viscerosensory inputs. Most neurons recorded did not exhibit ChR2-mediated responses, despite extensive hypothalamic axon/terminal labelling. In some NTS neurons, ChR2-mediated stimulation of hypothalamic efferents elicited glutamatergic, AMPA receptor mediated excitatory postsynaptic currents (ChR2-EPSCs). Responsive NTS neurons included both 2nd, and higher, order neurons and AT_1AR and few TH expressing neurons. All ChR2-EPSCs tested were blocked by TTX. Some TTX blocked ChR2-EPSCs could be recovered with the co-application 4AP, confirming monosynaptic connection between hypothalamic and NTS neurons. Superimposition of convergent inputs from hypothalamic and viscerosensory efferents resulted in summated EPSCs that would likely increase throughput probability of the viscerosensory signals at NTS neurons. The neural link between the hypothalamus and NTS comprises discreet glutamatergic input, including to TH positive and AT_1AR expressing NTS neurons.