Endogenous Inhibition of the Trigeminally-Evoked Neurotransmission to Cardiac Vagal Neurons

29 30 Stimulation of the nasal mucosa by airborne irritants or water evokes a pronounced bradycardia 31 accompanied by peripheral vasoconstriction and apnea. The dive response, which includes the 32 trigeminocardiac reflex, is among the most powerful autonomic responses. These responses slow the 33 heart rate and reduce myocardial oxygen consumption. While normally cardioprotective, exaggeration 34 of this reflex can be detrimental and has been implicated in cardiorespiratory diseases, including sudden 35 infant death syndrome (SIDS). An essential component of the diving response and trigeminocardiac 36 reflex is activation of the parasympathetic cardiac vagal neurons (CVNs) in the nucleus ambiguus that 37 control heart rate. This study examined the involvement of cholinergic receptors in trigeminally-evoked 38 excitatory post synaptic currents in CVNs in an in-vitro preparation from rats. CVNs were identified 39 using a retrograde tracer injected into the fat pads at the base of the heart .Application of the 40 acetylcholinesterase inhibitor, neostigmine, significantly decreased the amplitude of glutamatergic 41 neurotransmission to CVNs upon stimulation of trigeminal fibers. While nicotine did not have any 42 effect on the glutamatergic responses, the muscarinic acetylcholine receptor (mAChR) agonist, 43 bethanechol, significantly decreased the excitatory neurotransmission. Atropine, a mAChR antagonist, 44 facilitated these responses indicating this trigeminally-evoked brainstem pathway in-vitro is 45 endogenously inhibited by mAChRs. Tropicamide, a m4 mAChR antagonist, prevented the inhibitory 46 action of the muscarinic agonist bethanechol. These results indicate that the glutamatergic synaptic 47 neurotransmission in the trigeminally-evoked pathway to CVNs is endogenously inhibited in-vitro by 48 m4 mAChRs. 49 50 2 INTRODUCTION 51