Intrinsic and synaptic long-term depression of NTS relay of nociceptin- and capsaicin-sensitive cardiopulmonary afferents hyperactivity.
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 N-methyl-D: -aspartate (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.
Bantikyan
Armenak
A
Massachusetts Institute of Technology, Cambridge, 02139, USA.
Song
Gang
G
Feinberg-Zadek
Paula
P
Poon
Chi-Sang
CS
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D017774:Long-Term Potentiation; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D018847:Opioid Peptides / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D011957:Receptors, Opioid; D017552:Solitary Nucleus / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D050916:TRPV Cation Channels / Q000187:drug effects / Q000502:physiology; D000097629:Nociceptin
D002211:Capsaicin; D018847:Opioid Peptides; D011498:Protein Precursors; D016194:Receptors, N-Methyl-D-Aspartate; D011957:Receptors, Opioid; D050916:TRPV Cation Channels; D000097629:Nociceptin; C493922:Trpv1 protein, rat; C111148:nocistatin; C121527:prepronociceptin