Synaptic Characteristics Between Cortical Cells in the Rat Prefrontal Cortex and Axon Terminals from the Ventral Tegmental Area that Utilize Different Neurotransmitters

Abstract

Projections from the ventral tegmental area (VTA) have been demonstrated to terminate in the prefrontal cortex (PFC) and to be dopaminergic and/or γ-aminobutyric acidergic (GABAergic), forming a neural circuit implicated in certain memory and cognitive processes. However, it has not been determined whether γ-aminobutyric acid (GABA) and dopamine (DA) are localized in certain types of axon terminals from the VTA to the PFC. To determine the synaptic characteristics made by postsynaptic prefrontal cortical structures and mesoprefrontal fibers utilizing either GABA or DA, we performed a double-labeling method for electron microscopy, in which we combined peroxidase markers for anterograde tract-tracing with postembedding immunogold labeling for tyrosine hydroxylase, DA, and GABAin rats. The anterograde tract-tracing studies showed that tegmentocortical fibers from the VTA terminated as both symmetric and asymmetric axon terminals with the predominantly symmetric synaptic type in the prelimbic cortex of the rat. Furthermore, a study using the combination of anterograde tract-tracing and postembedding immunocytochemistry indicated that tegmentocortical axon terminals forming symmetric synapses were either GABAergic or dopaminergic, whereas a small fraction of tegmentocortical terminals ending as asymmetric synapses were not immunopositive for DA or GABA. These findings indicate that the mesocortical projections to the PFC exert an inhibitory effect on the spontaneous activity of PFC cells via symmetric synapses that use DA and GABA as neurotransmitters and that these projections also have as yet unknown effects via asymmetric synapses using other neurotransmitters.