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Volume 17, Number 14, Issue of July 15, 1997 pp. 5349-5356
Copyright ©1997 Society for Neuroscience

Phasic and Long-Term Depression in Brainstem Nucleus Tractus Solitarius Neurons: Differing Roles of AMPA Receptor Desensitization

Received Feb. 4, 1997; revised May 5, 1997; accepted May 7, 1997.

Zhongren Zhou¹, Jean Champagnat², and Chi-Sang Poon¹

¹ Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, and ² Biologie Fonctionnelle du Neurone, Institut Alfred Fessard, Centre National de la Recherche Scientifique, 91198 Gif-sur-Yvette, France

One important question concerning the homeostatic regulation of many physiological processes is whether the control mechanisms are purely reflexogenic or whether they may involve neural adaptation in the form of learning and memory in the brainstem. Using a brainstem slice preparation in the rat, we studied the modifiability of neural transmission in the first-order synapses of the medial and commissural nucleus tractus solitarius of the medulla. Sustained low-frequency stimulation (5 Hz) of primary afferent fibers in the tractus solitarius resulted in a phasic depression (accommodation) of synaptic strength as reflected by a concomitant decrease in the evoked excitatory postsynaptic potentials. In one group of neurons (type I), synaptic strength recovered rapidly after low-frequency stimulation, whereas in another group of neurons (type II), synaptic strength remained depressed for >30 min, i.e., manifesting long-term depression (LTD). The latter was switched into a short-term depression lasting 15-25 min after pharmacological blockade of NMDA receptor channels with D-APV or chelation of intracellular calcium ions with EGTA, whereas the accommodation phase was unaffected. Application of an AMPA receptor anti-desensitization agent cyclothiazide abolished the LTD, but not the accommodation response. These results suggest the presence of separate postsynaptic sites for the induction of LTD and accommodation, one being sensitive to cyclothiazide, whereas the other is not. Moreover, the maintenance of LTD is dependent on the level of intracellular Ca²⁺. These phasic and long-term synaptic plasticity in the nucleus tractus solitarius may play a role in the homeostatic regulation of cardiorespiratory functions.

Key words: nucleus tractus solitarius; cardiovascular control; baroreflex; respiratory control; chemoreflex; vagal reflex; autonomic regulation; homeostasis; brainstem; long-term depression; long-term potentiation; synaptic accommodation; phasic synaptic depression; synaptic plasticity; learning and memory; AMPA receptor desensitization; NMDA receptor; intracellular calcium

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