Responsiveness to nicotine of neurons of the caudal nucleus of the solitary tract correlates with the neuronal projection target

Abstract

<jats:p>The caudal nucleus of the solitary tract (NTS) is the key integrating center of visceral sensory-motor signaling supporting autonomic homeostasis. Two key projections of this nucleus are the parabrachial nucleus (PbN) and the dorsal motor nucleus of the vagus (DMV). The PbN integrates and relays viscerosensory information primarily to the forebrain, supporting behavioral, emotional, and endocrine responses to visceral events, while the DMV contains parasympathetic preganglionic cholinergic motoneurons that support primarily gastrointestinal reflexes. Subsets of caudal NTS neurons express presynaptic and somatodendritic nicotinic acetylcholine receptors (nAChRs). However, the anatomical identification of nicotine-responsive caudal NTS neurons has not been determined. This study used in vivo and ex vivo fluorescent tracing and slice patch-clamp electrophysiological recordings from anatomically identified caudal NTS neurons to test the hypothesis that the responsiveness of these cells to nicotine correlates with the target of their axonal projections. The results demonstrate that the majority of glutamatergic terminals that synapse on PbN-projecting caudal NTS neurons are unaffected by nicotine. Moreover, only a fraction of these cells express somatodendritic nAChRs. In contrast, the majority of DMV-projecting caudal NTS neurons exhibit robust presynaptic and somatodendritic responsiveness to nicotine. However, PbN-projecting neurons also exhibit significantly lower background frequencies of glutamatergic miniature postsynaptic currents than DMV-projecting neurons. Therefore, presynaptic unresponsiveness to nicotine may result from deficient glutamatergic innervation of PbN-projecting neurons. Nevertheless, the caudal NTS contains function-specific subsets of cells with target-specific responsiveness to nicotine. These results may support development of therapeutic strategies for selective targeting of specific autonomic pathways and impaired autonomic homeostasis.</jats:p>

Nicotine enhances inhibition of mouse vagal motor neurons by modulating excitability of premotor GABAergic neurons in the nucleus tractus solitarii

“…Gao and Smith 2010;Travagli et al 1991Travagli et al , 2006. In rats, DMV-projecting NTS neurons form the most populous nicotine-responsive group of neurons in the nucleus (Feng et al 2012;Feng and Uteshev 2014). Our data demonstrate that GABAergic NTS neurons in particular act as nicotine-sensitive, second-order viscerosensory neurons and that nicotine enhances synaptic excitation in premotor GABA neurons related to gastric projections.…”

“…Previous studies have suggested that nicotine effects in the NTS are differentially expressed, with neurons projecting to forebrain or parabrachial nucleus (PbN) being unaffected and neurons projecting to vagal motor neurons being excited by nicotinic receptor activation (Feng et al 2012;Feng and Uteshev 2014). To determine whether DMV-projecting, gastric motor-related NTS neurons were affected by nicotine, NTS neurons identified after gastric musculature inoculation with PRV614 were voltage-clamped at Ϫ70 mV in the presence of TTX and mEPSCs were examined for responses to focally applied nicotine.…”

“…Glutamate is the major excitatory neurotransmitter in the brain stem, and glutamatergic neurotransmission in the DVC can be modulated by multiple presynaptic ligand-gated receptors (Bach and Smith 2012; Bailey et al 2002Bailey et al , 2006bBlessing 1990;Browning et al 2006;Derbenev et al 2006) including nicotinic acetylcholine (ACh) receptors (nAChRs) (Feng et al 2012;Feng and Uteshev 2014;Kalappa et al 2011;Smith and Uteshev 2008). The majority of DMV-projecting caudal NTS neurons exhibit robust presynaptic and somatodendritic responsiveness to nicotine (Feng et al 2012;Feng and Uteshev 2014;Kalappa et al 2011).…”

“…The majority of DMV-projecting caudal NTS neurons exhibit robust presynaptic and somatodendritic responsiveness to nicotine (Feng et al 2012;Feng and Uteshev 2014;Kalappa et al 2011). Moreover, inhibitory synaptic inputs of an unidentified origin to DMV neurons are sensitive to nAChR activation in brain stem slices from rats (Bertolino et al 1997), but functional and anatomical specificity of circuits associated with such responses has not been investigated.…”

Building An Open-source Robotic Stereotaxic Instrument

“…In all, automating surgeries provides a number of benefits for a modest cost, and as such, is becoming an increasingly popular technique 10,11 . But it is important to recognize that the accuracy of the robot depends on quality machining, proper setup, and proper understanding of how CNC machines operate.…”