DOPAMINE NEURONS MAKE GLUTAMATERGIC SYNAPSES IN-VITRO

Interactions between dopamine and glutamate play prominent roles in me mory, addiction, and schizophrenia. Several lines of evidence have sug gested that the ventral midbrain dopamine neurons that give rise to th e major CNS dopaminergic projections may also be glutamatergic. To exa mine this possibility, we double immunostained ventral midbrain sectio ns from rat and monkey for the dopamine-synthetic enzyme tyrosine hydr oxylase and for glutamate; we found that most dopamine neurons immunos tained for glutamate, both in rat and monkey. We then used postnatal c ell culture to examine individual dopamine neurons. Again, most dopami ne neurons immunostained for glutamate; they were also immunoreactive for phosphate-activated glutaminase, the major source of neurotransmit ter glutamate. Inhibition of glutaminase reduced glutamate staining. I n single-cell microculture, dopamine neurons gave rise to varicosities immunoreactive for both tyrosine hydroxylase and glutamate and others immunoreactive mainly for glutamate, which were found near the cell b ody. At the ultrastructural level, dopamine neurons formed occasional dopaminergic varicosities with symmetric synaptic specializations, but they more commonly formed nondopaminergic varicosities with asymmetri c synaptic specializations. Stimulation of individual dopamine neurons evoked a fast glutamatergic autaptic EPSC that showed presynaptic inh ibition caused by concomitant dopamine release. Thus, dopamine neurons may exert rapid synaptic actions via their glutamatergic synapses and slower modulatory actions via their dopaminergic synapses. Together w ith evidence for glutamate cotransmission in serotonergic raphe neuron s and noradrenergic locus coeruleus neurons, the present results sugge st that glutamatergic cotransmission may be the rule for central monoa minergic neurons.