The Journal of Neuroscience, April 15, 2002, 22(8):3215-3226
Domoic Acid Lesions in Nucleus of the Solitary Tract:
Time-Dependent Recovery of Hypoxic Ventilatory Response and
Peripheral Afferent Axonal Plasticity
Zixi (Jack)
Cheng1,
Shang Z.
Guo1,
Andrew J.
Lipton1, and
David
Gozal1, 2
1 Kosair Children's Hospital Research Institute,
Department of Pediatrics, and 2 Department of Pharmacology
and Toxicology, University of Louisville School of Medicine,
Louisville, Kentucky 40202
The nucleus of the solitary tract (NTS) plays a pivotal role in the
ventilatory response to hypoxia (HVR). However, the effects of
excitotoxic lesions and the potential for functional recovery and
plasticity remain unknown. Domoic acid (DA) or vehicle were bilaterally
injected within the NTS of adult male Sprague Dawley rats. HVR (10%
O2) and anatomical changes were assessed at
5-90 d after surgery. DA induced dose-dependent HVR attenuations
(~70% at peak effect) that exhibited saturation at concentrations of 0.75-1.0 mM. However, although sodium cyanide-induced
ventilatory responses were virtually abolished, DA did not modify
baroreceptor gain. Consistent with ventilatory reductions, NTS neurons
showed a significant degeneration 3 d after DA injection. In
addition, the projection fields and the density of vagal afferent
terminals to the NTS, and the motor neurons in the dorsal motor nucleus of the vagus were substantially reduced at 15 d. At 30 d, no
functional or neural recovery were apparent. However, at day 60, the
reduction in HVR was only ~40% of control, and at 90 d, HVR
returned to control levels, paralleling regeneration of vagal afferent
terminals within the NTS. The regeneration was particularly prominent
in the commissural and dorsomedial subnuclei in the absence of cellular recovery. Thus, the integrity of the NTS is critical for HVR, spontaneous HVR recovery occurs after excitotoxic lesions in the NTS,
and vagal-glossopharyngeal terminal sprouting in the NTS may underlie
the anatomical substrate for such spontaneous functional recovery. The
adult brainstem/NTS has self-repairing capabilities and will compensate
for functional losses after structural damage by rewiring of its neural circuitry.
Key words:
hypoxic ventilatory response; brainstem; glutamate; excitotoxicity; baroreceptor; functional plasticity
Copyright © 2002 Society for Neuroscience 0270-6474/02/2283215-12$05.00/0
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