Afferent information initiating the cardiorespiratory responses during nasal stimulation projects from the nasal passages to neurons within the trigeminal medullary dorsal horn (MDH) via the anterior ethmoidal nerve (AEN). Central AEN terminals are thought to release glutamate to activate the MDH neurons. This study was designed to determine which neurotransmitter receptors (AMPA, kainate, or NMDA glutamate receptor subtypes or the Substance P receptor NK1) are expressed by these activated MDH neurons. Fos was used as a neuronal marker of activated neurons, and immunohistochemistry combined with epifluorescent microscopy was used to determine which neurotransmitter receptor subunits were coexpressed by activated MDH neurons. Results indicate that, during nasal stimulation with ammonia vapors in urethane-anesthetized Sprague-Dawley rats, activated neurons within the superficial MDH coexpress the AMPA glutamate receptor subunits GluA1 (95.8%) and GluA2/3 (88.2%), the NMDA glutamate receptor subunits GluN1 (89.1%) and GluN2A (41.4%), and NK1 receptors (64.0%). It is therefore likely that during nasal stimulation the central terminals of the AEN release glutamate and substance P that then produces activation of these MDH neurons. The involvement of AMPA and NMDA receptors may mediate fast and slow neurotransmission, respectively, while NK1 receptor involvement may indicate activation of a nociceptive pathway. 1. Introduction The diving response, an autonomic reflex characterized by apnea, bradycardia, and increased peripheral vascular resistance, is initiated through nasal stimulation or when animals submerge under water [1]. Afferent information involved in initiating this response projects from the nasal mucosa to the spinal trigeminal nucleus via the anterior ethmoidal nerve (AEN), a branch of the ophthalmic division of the trigeminal nerve [2]. The central projections of the AEN terminate within the spinal trigeminal nucleus caudalis [3]. This area is also known as the medullary dorsal horn (MDH) due to its functional and anatomical similarities with the spinal dorsal horn (SDH) [4]. Second-order neurons within the MDH are activated both during voluntary diving in conscious animals [5] and nasal stimulation in anesthetized animals [6–8]. It is likely that excitatory amino acids serve as neurotransmitters at synapses within the MDH that are part of this response, as injection of kynurenate, a general excitatory amino acid antagonist, into the MDH abolishes the cardiorespiratory responses to nasal stimulation [9]. More specifically, it is likely that
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