Convergent Inputs from the Hippocampus and Thalamus to the Nucleus Accumbens Regulate Dopamine Neuron Activity

PVT-induced increases in dopamine neuron transmission are attributable to glutamatergic projections to the NAc. Three parameters of activity were recorded: (A) population activity (average number of spontaneously firing dopamine neurons per electrode track), (B) average firing rate, and (C) average percentage spikes firing in a burst. NMDA activation of the PVT causes a significant increase in the VTA dopamine neuron population activity, which is likely caused by a glutamatergic projection in the NAc because it is attenuated by KA administration into the NAc, but not the vHipp. Following PVT activation (with NMDA), we observed significant increases in the average firing rate and percentage bursting only following glutamatergic blockade with KA in the vHipp. D, Schematic demonstrating the site of injection adjacent to the PVT (top), and within the NAc (middle), and vHipp (bottom). *p < 0.05 compared with respective vehicle control. #p < 0.05 compared with control-vehicle/PVT-NMDA.

Chemogenetic activation of the PVT to the NAc, but not the PVT-mPFC, pathway increases VTA dopamine neuron population activity. Three parameters of activity were recorded: (A) population activity (average number of spontaneously firing dopamine neurons per electrode track), (B) average firing rate, and (C) average percentage spikes firing in a burst. Chemogenetic activation of the PVT-NAc pathway causes a significant increase in VTA dopamine neuron population activity. In contrast, activation of the PVT-mPFC pathway did not affect VTA dopamine neuron population activity. D, Schematic representation of the viral injection (AAV-Gq-DREADD) to the PVT and stainless steel cannula used to target the mPFC or NAc (for CNO administration). E, Histological verification of viral reporter expression demonstrating cell bodies in the PVT (left) and terminals in afferent targets in the mPFC (right). *p < 0.05 compared with control.

Chemogenetic activation of the pathways from the vHipp and the PVT to the NAc produce increases in VTA dopamine neuron population activity. Three parameters of activity were recorded: (A) population activity (average number of spontaneously firing dopamine neurons per electrode track), (B) average firing rate, and (C) average percentage spikes firing in a burst. Consistent with previous reports, activation of the vHipp-NAc pathway produces a significant increase in VTA dopamine neuron population activity. Here we demonstrate that activation of the PVT-NAc pathway produces a similar effect on dopamine neuron activity. D, Schematic representation of the bilateral viral injections to the vHipp or PVT (AAV-DIO-Gq-DREADD) and NAc (HSV-Cre). E, Histological verification of viral reported expression demonstrating a NAc-projecting neuron in the PVT. *p < 0.05 compared with control.

PVT activity is required for the vHipp to increase dopamine neuron activity. Three parameters of activity were recorded: (A) population activity (average number of spontaneously firing dopamine neurons per electrode track), (B) average firing rate, and (C) and average percentage spikes firing in a burst. NMDA activation of the vHipp causes a significant increase in VTA dopamine neuron population activity, which is attenuated by TTX inactivation of the PVT. Additionally, vHipp activation significantly increased the firing rate and percentage bursting, but only following TTX inactivation of the PVT. D, Schematic demonstrating the site of injection within the PVT (top) and vHipp (bottom). *p < 0.05 compared with vHipp-NMDA/PVT-vehicle. #p < 0.05 compared with PVT-vehicle/vHipp-vehicle.

The NAc receives convergent input from the PVT and the vHipp. A, Schematic demonstrating the sites of stimulation adjacent to the PVT (top) and within vHipp (bottom). B, Representative trace from a putative medium spiny neuron responding to stimulation from the PVT and vHipp. C, Percentage of cells that responded to stimulation from the PVT, vHipp, or both.

Inactivation of the PVT attenuates aberrant dopamine neuron activity in two different rodent models of schizophrenia. Three parameters of activity were recorded: (A) population activity (average number of spontaneously firing dopamine neurons per electrode track), (B) average firing rate, and (C) average percentage spikes firing in a burst. The MAM and poly I:C rodent models of schizophrenia display a significant increase in VTA dopamine neuron population activity, which is attenuated by TTX inactivation of the PVT. D, Schematic demonstrating the site of injection adjacent to the PVT. *p < 0.05 compared with Prenatal-vehicle. #p < 0.05 compared with PVT-vehicle.