The paraventricular nucleus of the thalamus (PVT) participates in the functional integration of limbic cortical and striatal circuitry. In the rat, the PVT projects to the deep layers of the medial prefrontal cortex (PFC) and to the shell of the nucleus accumbens (NAc). However, the synaptic organization of PVT afferents within these regions remains undescribed. Furthermore, although dopamine (DA) modulates excitatory glutamate transmission in both areas, possible anatomic substrates for specific DA modulation of PVT inputs have not yet been investigated. To address these issues, immunoperoxidase labeling for tyrosine hydroxylase (TH) in DA axons was combined with anterograde tract-tracing, either by biotinylated dextran amine (BDA) labeled with immunogold-silver or by degeneration after lesions of the PVT. In both regions, and with either tracing method, PVT terminals formed primarily asymmetric axospinous synapses; in the NAc, a proportion of PVT terminals also synapsed onto dendrites. PVT profiles in both regions were often seen in direct apposition to TH-immunoreactive axons; this association was more evident in the NAc where the DA innervation is denser. Within the PFC, PVT profiles and TH-labeled axons were occasionally apposed to the same dendrites, but synaptic specializations were not typically seen at these seeming points of convergence. Within the NAc, PVT profiles occasionally made synapses onto spines and distal dendrites that received convergent synapses from TH-immunoreactive varicosities. These findings represent the first demonstration of postsynaptic convergence between DA and thalamic afferents to a striatal region and are consistent with direct synaptic modulation of PVT transmission by DA in the NAc but not the PFC.

For normal regulation of motor, affective, and cognitive functions, dopamine provides an essential modulation of glutamate transmission within multiple brain regions. This paper will review three principal anatomical substrates for such interactions. First, dopamine modulates the activity of glutamate neurons within the cerebral cortex. Evidence will be reviewed for dopamine regulation of pyramidal neurons in the prefrontal cortex via synaptic and extrasynaptic mechanisms and through indirect effects mediated by GABA cells. Second, glutamate neurons innervate dopamine cells within the ventral tegmental area. Evidence will be described for selective glutamate input from the prefrontal cortex or the brain stem tegmentum to different populations of dopamine cells. The third level of interaction occurs within target regions via convergent synaptic or extrasynaptic regulation of common neurons. Such convergence will be reviewed for the basal ganglia, prefrontal cortex, and amygdala. Together, these substrates for glutamate-dopamine interactions provide several mechanisms for normal regulation of brain function. Sites of modulatory interaction between dopamine and glutamate also suggest circuit alterations that might contribute to the pathophysiology of mental health disorders and provide potential sites for therapeutic intervention in these conditions.

Projections from the prefrontal cortex (PFC) to the amygdala (AMG) regulate affective behaviors in a manner that is modulated by dopamine (DA). Although PFC and DA inputs overlap within the basolateral nucleus (BLA) and intercalated cell masses (ICMs), the spatial relationship between these afferents has not been investigated, nor is it known how DA D1 (D1R) and D2 (D2R) receptors are localized in relationship to PFC terminals. We therefore combined tract-tracing from the rat PFC to the AMG with immunocytochemical labeling of tyrosine hydroxylase (TH) to identify presumed DA axons or D1R and D2R. In both the ICMs and BLA, PFC terminals formed asymmetric synapses onto spines that typically did not receive secondary synaptic inputs. TH-immunoreactive (-ir) fibers in the adjacent neuropil typically contacted different structures. Although PFC and TH-ir axons were sometimes apposed to the same dendrites or to each other, PFC terminals only rarely synapsed onto dendrites that also received synapses from TH-ir axons. D1R-ir spines and dendrites were observed commonly within the ICMs but less frequently within the BLA, and PFC axons in the ICMs occasionally synapsed onto D1R-ir spines. Within both regions, D2R-ir spines, dendrites, and axons were observed. PFC terminals occasionally contained presynaptic labeling for D2R but were not observed to synapse onto D2R-ir targets. The infrequent observation of synaptic convergence between PFC and presumed DA terminals within the AMG suggests that DA modulates PFC inputs primarily via extrasynaptic mechanisms, a conclusion supported by the localization of D2R within and D1R postsynaptic to PFC terminals.

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The rhinal cortices constitute the main route for impulse traffic to and from the hippocampus. Tracing studies have revealed that the perirhinal cortex forms strong reciprocal connections with the neo- and entorhinal cortex (EC). However, physiological investigations indicate that perirhinal transmission of neocortical and EC inputs occurs with a low probability. In search of an explanation for these contradictory findings, we have analyzed synaptic connections in this network by combining injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHAL) into the neocortex, area 36, or area 35 with gamma-aminobutyric acid (GABA) immunocytochemistry and electron microscopic observations. Within area 36, neocortical axon terminals formed only asymmetric synapses, usually with GABA-negative spines (87%), and less frequently with GABA-immunopositive (GABA+) dendrites (13%). A similar synaptic distribution was observed within area 35 except that asymmetric synapses onto GABA+ dendrites were more frequent (23% of synapses). Examination of the projections from area 36 to area 35 and from both regions to the EC revealed an even higher incidence of asymmetric synapses onto GABA+ dendrites (35 and 32%, respectively) than what was observed in the neocortical projection to areas 36 and 35. Furthermore, some of the neocortical and perirhinal terminals containing PHAL and GABA immunolabeling formed symmetric synapses onto GABA-negative dendrites in their projection sites (neocortex to area 35, 16%; area 36 to 35, 7%; areas 36-35 to EC, 12%). Taken together, these findings suggest that impulse transmission through the rhinal circuit is subjected to strong inhibitory influences, reconciling anatomical and physiological data about this network.