Stimulus Pattern Modulats Dopamine Release In Vivo

Dopamine is an attractive and important neurotransmitter in neurobiological study. It involves in multiple functions ranging from movement, cognition, respiration and reinforcement to neurological disorders. All of these functions depend on the synergy of neural activity and dopamine release. This involves two issues: how neural activities modulate dopamine release and what is the function of dopamine release to neural activity. In order to elucidate these two questions respectively, we employed two preparations, substantia nigra-striatum and carotid body (CB), where dopamine is the predominant transmitter.First, we tried to reveal how stimulus patterns modulate transmitter release in the central nervous system. Amperometry was applied to evaluate dopamine release in the rat striatum, in response to electrical stimulation of the medial forebrain bundle. The stimulus pattern was defined by the four parameters, number and frequency of stimuli pulses, number of bursts, and inter-burst interval. We found that besides frequency and pulse number, for a given number of stimuli, the number of bursts effectively modulated dopamine release (burst effect). Furthermore, this burst effect was modulated by stimulus numbers, frequency and inter-burst interval. Cocaine and nomifensine, inhibitors of dopamine transporter, enhanced the burst effect. We proposed that the burst effect indicates the secretion efficiency and may play an important role in information transfer in neural networks.Second, we developed a technique to quantify the catecholamines release of rat CB in vivo. We studied the function of dopamine to sinus nerve during normoxia and hypoxia. To our surprise, hypoxia induces a rapid decrease in dopamine release in vivo, in stead of increase in isolated tissue or cells. Furthermore, the hypoxia-induced dopamine signal is reversed from decrease to increase after cutting the sinus nerve, indicating that a nerve feedback signal is responsible for the difference between isolated tissue/cell and the intact CB in vivo. Then, we set out to investigate the function of dopamine to sinus nerve under physiology condition. The activity of sinus nerve was suppressed by direct application of dopamine and enhanced by haloperidol, an inhibitor of dopamine receptor. These experiments suggest that dopamine is an inhibitory transmitter to sinus nerve in normoxia. The inhibition is decreased when hypoxia reduced the dopamine release. Consequently, the carotid sinus nerve will be exciting and trigs the chemoreflex.In summery, synergy of dopamine release and neural activity is essential to brain function. And in vivo experiment provides us an ideal system to function study in physiology conditions.