Garcia-Munoz M, Young S J, Groves P M
University of California, School of Medicine, Department of Psychiatry, San Diego, La Jolla 92093.
Brain Res. 1991 Jun 14;551(1-2):195-206. doi: 10.1016/0006-8993(91)90933-m.
Glutamatergic cortical and dopaminergic nigral afferents converge onto neurons of the neostriatum forming synapses in close proximity. Studies, mainly using pharmacological methods, suggest presynaptic interactions between these afferents. The influence of dopaminergic transmission on the cortical terminal fields in the striatum was assessed electrophysiologically using the terminal excitability method. Antidromic action potentials recorded from neurons in the prefrontal cortex were elicited by bipolar electrical stimulation (250 microns wire, 0.5 mm tip separation) of the cortical terminal field in the contralateral dorsomedial neostriatum. Threshold excitability was defined as the minimum current sufficient to elicit 95-100% antidromic response on non-collision trials. Under control conditions, the mean threshold current was 1.7 +/- 0.2 mA. Drugs were applied in a volume of 312 nl delivered over 5 min to the striatal stimulation site. Following local striatal administration of amphetamine (10 microM) or electrical stimulation of the nigrostriatal pathway (1-2 pulses, 1.5 mA/0.5 ms/1 Hz) an increase in striatal stimulating current was required in order to reinstate threshold levels of antidromic response. This decrease in the excitability of corticostriatal afferents could be reversed by local infusion of haloperidol (1 microM) or L-sulpiride (10 nM) and did not occur following depletion of dopamine stores with alpha-methylparatyrosine and reserpine. The possible participation of postsynaptic dopamine receptor stimulation was ruled out as these effects were still seen in animals with kainic acid induced lesions of the striatum. In addition, terminal excitability was not modified by the muscarinic agonist carbachol (10 microM). Striatal administration of apomorphine (10 microM) decreased terminal excitability similar to amphetamine. The specific D-2 agonist, quinpirole (10-20 microM) did not affect excitability. These results indicate that manipulations which have been shown to increase the release of endogenous dopamine decrease the excitability of prefrontal corticostriatal afferents by stimulation of presynaptic dopamine receptors which are insensitive to low doses of quinpirole but sensitive to L-sulpiride and apomorphine. The mechanisms underlying dopamine-induced changes in terminal excitability are likely to be similar to those which have been shown to alter conductance at postsynaptic sites.
