Selected Contribution: Neuroplasticity in nucleus tractus solitarius neurons after episodic ozone exposure in infant primates

Abstract

Acute ozone exposure evokes adverse respiratory responses, particularly in children. With repeated ozone exposures, however, despite the persistent lung inflammation and increased sensory nerve excitability, the central nervous system reflex responses, i.e., rapid shallow breathing and decreased lung function, adapt, suggesting changes in central nervous system signaling. We determined whether repeated ozone exposures altered the behavior of nucleus tractus solitarius (NTS) neurons where reflex respiratory motor outputs are first coordinated. Whole cell recordings were performed on NTS neurons in brain stem slices from infant monkeys exposed to filtered air or ozone (0.5 ppm, 8 h/day for 5 days every 14 days for 11 episodes). Although episodic ozone exposure depolarized the membrane potential, increased the membrane resistance, and increased neuronal spiking responses to depolarizing current injections ( P < 0.05), it decreased the excitability to vagal sensory fiber activation ( P < 0.05), suggesting a diminished responsiveness to sensory transmission, despite overall increases in excitability. Substance P, implicated in lung and NTS signaling, contributed to the increased responsiveness to current injections but not to the diminished sensory transmission. The finding that NTS neurons undergo plasticity with repeated ozone exposures may help to explain the adaptation of the respiratory motor responses.

Hyperbaric oxygen and chemical oxidants stimulate CO2/H+-sensitive neurons in rat brain stem slices

“…tive stress that disrupts breathing, particularly in children, increased R in and depolarized monkey NTS neurons (11). Together, these observations suggest that the effects of oxidative stress on respiration could be, in part, mediated by CO 2 /H ϩ -chemosensitive SC neurons.…”

Stress and atopic disorders

“…Airways function in response to stimuli, including irritants, allergens, and inflammatory mediators. Chen et al 19,20 have demonstrated the ability of the nucleus tractus solitarius, a CNS region containing neurons that process lung sensory signals, to undergo marked changes in excitability in the face of extended exposure to irritants (ie, allergen exposure, ozone exposure, and tobacco smoke). These toxicants share commonalities in the responses they may illicit in the airways (eg, local release of inflammatory mediators, oxidative stress, and activation of sensory neurons) that may contribute to the respiratory inflammatory and motor response.…”

New insights into the electrophysiology of brainstem circuits controlling blood pressure

“…NTS neurons that receive afferent inputs from lung and tracheal receptors exhibit exaggerated responses to stimulation of airway receptors following chronic exposures to airway pollutants (eg, cigarette smoke) [12]. NTS neurons recorded in a brain-slice preparation from infant primates episodically exposed to ozone for 14 days exhibited a decreased tendency to respond to synaptic activation coupled with an increased intrinsic excitability [13]. Chronic exposure to hypoxia (7 days at 10% oxygen) induces the opposite changes in NTS neurons receiving arterial chemoreceptor inputs: an increased response to synaptic excitation and a reduced intrinsic excitability (Zhang and Mifflin, Unpublished data).…”