Convergence and Segregation of Excitatory and Inhibitory Afferents in the Paraventricular Thalamic Nucleus.

The paraventricular thalamic nucleus (PVT) integrates subcortical signals related to arousal, stress, addiction, and anxiety with top-down cortical influences. Increases or decreases in PVT activity exert profound, long-lasting effects on behavior related to motivation, addiction, and homeostasis. Yet the sources of its subcortical excitatory and inhibitory afferents, their distribution within the PVT, and their integration with layer-specific cortical inputs remain unclear. Using transgenic male and female mice selective for GABAergic and glutamatergic neurons, or for different cortical layers, we found that the input organization of PVT is unique among thalamic nuclei. PVT received subcortical GABAergic and glutamatergic inputs from multiple, distinct hypothalamic and brainstem regions. Most regions provided either excitatory or inhibitory afferents; however, subcortical inputs with dual components have also been found. Most of these subcortical inputs selectively targeted the core region of the PVT that contained large number of densely packed calretinin-positive (CR+) neurons. Cortical afferents to PVT displayed layer-specific segregation. Layer 5 neurons of the medial prefrontal cortex preferentially innervated the CR+ core, whereas layer 6 input was more abundant in the transition zone between PVT and the mediodorsal nucleus. These findings demonstrate extensive convergence of excitatory and inhibitory inputs from diverse subcortical sources, selectively, in a sharply delineated CR+ core region of PVT which is also under strong top-down control from layer 5. This unique organization may explain why the CR+ PVT core serves as a critical bottleneck in the subcortex-cortex communication involved in affective behavior.