No abstract

Midbrain dopamine neurons in vivo discharge in a single-spike firing pattern or in a burst-firing pattern. Such activity in vivo strikingly contrasts with the pacemaker activity of the same dopamine neurons recorded in vitro. We have recently shown that burst activity in vivo of midbrain dopamine neurons is due to the local activation of excitatory amino acid receptors, as microapplication of the broad-spectrum antagonist of excitatory amino acids, kynurenic acid, strongly regularized the spontaneous firing pattern of these dopamine neurons. In the present study, we investigated which subtypes of excitatory amino acid receptors are involved in the burst-firing of midbrain dopamine neurons in chloral hydrate-anaesthetized rats, iontophoretic or pressure microejections of 6-cyano, 7-nitroquinoxaline-2,3-dione (CNQX), a non-N-methyl-D-aspartate (NMDA) receptor antagonist, did not alter the spontaneous burst firing of dopamine neurons (n = 36). In contrast, similar ejections of (+-)2-amino,5-phosphonopentanoic acid (AP-5), a specific antagonist at NMDA receptors, markedly regularized the firing pattern by reducing the occurrence of bursts (n = 52). In addition, iontophoretic ejections of NMDA, but not kainate or quisqualate, elicited a discharge of these dopamine neurons in bursts (n = 20, 12 and 14, respectively). These data suggest that burst-firing of midbrain dopamine neurons in vivo results from the tonic activation of NMDA receptors by endogenous excitatory amino acids. In view of the critical dependency of catecholamine release on the discharge pattern of source neurons, excitatory amino acid inputs to midbrain dopamine neurons may constitute a major physiological substrate in the control of the dopamine level in target areas.

The effect of 5-HT on activity of noradrenergic locus coeruleus (LC) neurons was studied using microiontophoretic and micropressure drug application in anesthetized rats. 5-HT had no consistent effect on LC spontaneous discharge, eliciting a modest decrease overall. However, 5- HT reliably attenuated responses of LC neurons to excitatory amino acids (EAAs), one of the major classes of transmitters in afferents to these neurons. This effect was specific for EAA responses because it occurred for glutamate and kainate but not for ACh. In contrast, iontophoretic norepinephrine (NE) selectively attenuated spontaneous activity but not responses evoked by either glutamate or ACh. The responsiveness of LC neurons to EAAs as quantified by a response- contrast measure (evoked excitation/basal activity) was markedly reduced by 5-HT, but was increased by NE. For ACh, such responsiveness of LC cells was not changed by 5-HT, but was increased by NE. The effects of 5-HT were prevented and reversed by iontophoretically applied antagonists of 5-HT receptors, methysergide and methiothepin. Thus, 5-HT appears to selectively interact with EAA responses of LC neurons, acting as a filter to attenuate LC activity linked to its major EAA inputs while allowing other channels afferent to the LC (e.g., those utilizing ACh) to be expressed.