Intrinsic and Synaptic Long-Term Depression of NTS Relay of Nociceptin-Sensitive and Capsaicin-Sensitive Cardiopulmonary Afferents Hyperactivity

synaptic long-term depression of NTS relay of nociceptin-and capsaicin-sensitive cardiopulmonary afferents hyperactivity. Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. ABSTRACT The nucleus tractus solitarius (NTS) in the caudal medulla is a gateway for a variety of cardiopulmonary afferents important for homeostatic regulation and defense against airway and cardiovascular insults, and is a key central target potentially mediating the response habituation to these inputs. Here, whole-cell and field population action potential recordings and infrared imaging in rat brainstem slices in vitro revealed a compartmental pain-pathway-like organization of capsaicin-facilitated vs. nocistatin-facilitated/nociceptin-suppressed neuronal clusters in an NTS region which receives cardiopulmonary A-and C-fiber afferents with differing capsaicin sensitivities. All capsaicin-sensitive neurons and a fraction of nociceptin-sensitive neurons expressed NMDA receptor-dependent synaptic long-term depression (LTD) following afferent stimulation. All neurons also expressed activity-dependent decrease of excitability (intrinsic LTD), which converted to NMDA receptor-dependent intrinsic long-term potentiation after GABA A receptor blockade. Thus, distinct intrinsic and synaptic LTD mechanisms in the NTS specific to the relay of A-or C-fiber afferents may underlie the response habituation to persistent afferents hyperactivity that are associated with varying physiologic challenges and cardiopulmonary derangements — including hypertension, chronic cough, asthmatic bronchoconstriction, sustained elevated lung volume in chronic obstructive pulmonary disease or in continuous positive-airway-pressure therapy for sleep apnea, metabolic acidosis, and prolonged exposure to hypoxia at high altitude.