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Serotonergic, Cholinergic, and Prenatal Nicotine Modulation of the Trigeminocardiac Reflex Open Access

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Stimulation of the trigeminal nerve evokes a dramatic decrease in heart rate and blood pressure, and this reflex has generally been termed the trigeminocardiac reflex. Activation of this reflex, in which the nasal mucosa is stimulated with water or air-borne chemical irritants, evokes a pronounced bradycardia, mediated by increased parasympathetic cardiac activity, and is the most powerful autonomic reflex. However, exaggeration of this protective response could be detrimental and has been implicated in Sudden Infant Death Syndrome (SIDS). Despite the importance and strength of the trigeminocardiac reflex, there is little information about the cellular mechanisms and brain stem pathways that constitute this reflex. Stimulation of trigeminal afferent fibers and the evoked excitatory glutamatergic postsynaptic currents were recorded in cardiac vagal neurons in an in vitro brainstem slice preparation. This synaptic pathway is robust was found that this reflex pathway is differentially modulated by endogenous activation of 5-HT1A and 5-HT2A/C receptors. Interestingly, nicotine did not have any effect on the excitatory glutamatergic responses; however, results indicated that this pathway is endogenously inhibited by M4 muscarinic acetylcholine receptors. Results in this dissertation also elucidated the role of fetal nicotine exposure and indicated that activation of both 5-HT1A and 5-HT2A/C receptors significantly facilitate the trigeminocardiac reflex pathway. To determine the neurons involved in this pathway we used a UV photo-uncaging system and found an area corresponding to the border of the interpolaris portion of the trigeminal nucleus and the spinal trigeminal tract demonstrated an increase in glutamatergic frequency in cardiac vagal neurons upon photo-uncaging of glutamate in this focal region. The work presented here establishes a neurochemical pathway between trigeminal afferent stimulation and parasympathetic control of heart rate. I discovered specific serotonergic and muscarinic receptors involved, as well as mechanisms by which prenatal nicotine exposure can alter the trigeminocardiac reflex. These results identify the neurons responsible for the glutamatergic neurotransmission in the trigeminocardiac reflex pathway that can potentially lead to an exaggeration of this powerful autonomic reflex as seen in diseases such as SIDS.

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