Gilbert J. Kirouac

The shell of the nucleus accumbens (NAcSh) regulates motivation and reward via its dense projection to the ventral pallidum (VP). This ventral striatopallidal system has also been shown to regulate the activity of midbrain dopamine neurons and the release of dopamine in the NAcSh. The present study applied monosynaptic rabies tracing in the rat to quantify the brain‐wide sources of synaptic input to neurons in the medial NAcSh that project to the ventromedial VP. The ventral subiculum of the hippocampus (vSub) was the largest source of input cells to the NAcSh‐VP projection neurons. Anterograde tracing of vSub‐NAcSh projection neurons demonstrated that their fibers terminated densely in the NAcSh largely avoiding other regions of the striatum. Another relatively strong source of input cells included the anterior part of the paraventricular nucleus of the thalamus (aPVT). The CA1, lateral septal nucleus, VP, paratenial thalamic nucleus, bed nucleus of the stria terminalis, lateral preoptic area and dorsomedial nucleus of the hypothalamus were moderately strong sources of input neurons. The prefrontal cortex, amygdala, and the basolateral nucleus of the amygdala were found to be relatively weak sources of input. A lack of sex differences for all the sources of input identified indicates that there is no apparent sexual dimorphism in the afferents to the striatopallidal system. In summary, the vSub and the aPVT are the major sources of cortical and thalamic monosynaptic inputs to the NAcSh‐VP projection neurons where these inputs converge to regulate behavior and dopamine release in the NAcSh.

The paraventricular nucleus of the thalamus (PVT) projects to areas of the forebrain involved in regulating behavior. Homeostatic challenges and salient cues activate the PVT and evidence shows that the PVT regulates appetitive and aversive responses. The brainstem is a source of afferents to the PVT and the present study was done to determine if the lateral parabrachial nucleus (LPB) is a relay for inputs to the PVT. Retrograde tracing experiments with cholera toxin B (CTB) demonstrate that the LPB contains more PVT projecting neurons than other regions of the brainstem including the catecholamine cell groups. The hypothesis that the LPB is a relay for signals to the PVT was assessed using an intersectional monosynaptic rabies tracing approach. Sources of inputs to LPB included the reticular formation; periaqueductal gray (PAG); nucleus cuneiformis; and superior and inferior colliculi. Distinctive clusters of input cells to LPB-PVT projecting neurons were also found in the dorsolateral bed nucleus of the stria terminalis (BSTDL) and the lateral central nucleus of the amygdala (CeL). Anterograde viral tracing demonstrates that LPB-PVT neurons densely innervate all regions of the PVT in addition to providing collateral innervation to the preoptic area, lateral hypothalamus, zona incerta and PAG but not the BSTDL and CeL. The paper discusses the anatomical evidence that suggests that the PVT is part of a network of interconnected neurons involved in arousal, homeostasis, and the regulation of behavioral states with forebrain regions potentially providing descending modulation or gating of signals relayed from the LPB to the PVT.

The paraventricular nucleus of the thalamus (PVT) projects to areas of the forebrain involved in behavior. Homeostatic challenges and salient cues activate the PVT and evidence shows that the PVT regulates appetitive and aversive responses. The brainstem is a source of afferents to the PVT and the present study was done to determine if the lateral parabrachial nucleus (LPB) is a relay for inputs to the PVT. Retrograde tracing experiments with cholera toxin B (CTB) demonstrate that the LPB contains more PVT projecting neurons than other regions of the brainstem including the catecholamine cell groups. The hypothesis that the LPB is a relay for brainstem signals to the PVT was assessed using an intersectional monosynaptic rabies tracing approach. Sources of inputs included the reticular formation, periaqueductal gray (PAG), nucleus cuneiformis, superior and inferior colliculi, and the LPB. Distinctive clusters of input cells to LPB-PVT projecting neurons were also found in the dorsolateral bed nucleus of the stria terminalis (BSTDL) and the lateral central nucleus of the amygdala (CeL). Anterograde viral tracing demonstrates that LPB-PVT neurons densely innervate all of the PVT in addition to providing collateral innervation to the preoptic area, lateral hypothalamus, zona incerta and PAG but not the BSTDL and CeL. The paper discusses the anatomical evidence that suggests that the PVT is part of a network of interconnected neurons involved in arousal, homeostasis, and the regulation of behavioral states with forebrain regions potentially providing descending modulation or gating of signals relayed from the LPB to the PVT.

The paraventricular nucleus of the thalamus (PVT) projects to areas of the forebrain involved in behavior. Homeostatic challenges and salient cues activate the PVT and evidence shows that the PVT regulates appetitive and aversive responses. The brainstem is a source of afferents to the PVT and the present study was done to determine if the lateral parabrachial nucleus (LPB) is a relay for inputs to the PVT. Retrograde tracing experiments with cholera toxin B (CTB) demonstrate that the LPB contains more PVT projecting neurons than other regions of the brainstem including the catecholamine cell groups. The hypothesis that the LPB is a relay for brainstem signals to the PVT was assessed using an intersectional monosynaptic rabies tracing approach. Sources of inputs included the reticular formation, periaqueductal gray (PAG), nucleus cuneiformis, superior and inferior colliculi, and the LPB. Distinctive clusters of input cells to LPB-PVT projecting neurons were also found in the dorsolateral bed nucleus of the stria terminalis (BSTDL) and the lateral central nucleus of the amygdala (CeL). Anterograde viral tracing demonstrates that LPB-PVT neurons densely innervate all of the PVT in addition to providing collateral innervation to the preoptic area, lateral hypothalamus, zona incerta and PAG but not the BSTDL and CeL. The paper discusses the anatomical evidence that suggests that the PVT is part of a network of interconnected neurons involved in arousal, homeostasis, and the regulation of behavioral states with forebrain regions potentially providing descending modulation or gating of signals relayed from the LPB to the PVT.

Editorial: Advances in Understanding of the Functions of the Paraventricular Thalamic Nucleus

Neurons in the paraventricular nucleus of the thalamus (PVT) respond to emotionally salient events and project densely to subcortical regions known to mediate adaptive behavioral responses. The areas of the forebrain most densely innervated by the PVT include striatal-like subcortical regions that consist of the shell of the nucleus accumbens (NAcSh), the dorsolateral region of the bed nucleus of the stria terminalis (BSTDL) and the lateral-capsular division of the central nucleus of the amygdala (CeL). A recent tracing experiment demonstrated that the PVT is composed of two intermixed populations of neurons that primarily project to either the dorsomedial (dmNAcSh) or ventromedial region of the NAcSh (vmNAcSh) with many of the vmNAcSh projecting neurons providing collateral innervation of the BSTDL and CeL. The present study used triple injections of the retrograde tracer cholera toxin B to provide a detailed map of the location of PVT neurons that provide collaterals to the vmNAcSh, BSTDL and CeL. These neurons were intermixed throughout the PVT and did not form uniquely localized subpopulations. An intersectional viral anterograde tracing approach was used to demonstrate that regardless of its presumed target of innervation (dmNAcSh, vmNAcSh, BSTDL, or CeL), most neurons in the PVT provide collateral innervation to a common set of forebrain regions. The paper shows that PVT-dmNAcSh projecting neurons provide the most divergent projection system and that these neurons express the immediate early gene product cFos following an aversive incident. We propose that the PVT may regulate a broad range of responses to physiological and psychological challenges by simultaneously influencing functionally diverse regions of the forebrain that include the cortex, striatal-like regions in the basal forebrain and a number of hypothalamic nuclei.

The brain anxiety network is composed of a number of interconnected cortical regions that detect threats and execute appropriate defensive responses via projections to the shell of the nucleus accumbens (NAcSh), dorsolateral region of the bed nucleus of the stria terminalis (BSTDL) and lateral region of the central nucleus of the amygdala (CeL). The paraventricular nucleus of the thalamus (PVT) is anatomically positioned to integrate threat- and arousal-related signals from cortex and hypothalamus and then relay these signals to neural circuits in the NAcSh, BSTDL, and CeL that mediate defensive responses. This review describes the anatomical connections of the PVT that support the view that the PVT may be a critical node in the brain anxiety network. Experimental findings are reviewed showing that the arousal peptides orexins (hypocretins) act at the PVT to promote avoidance of potential threats especially following exposure of rats to a single episode of footshocks. Recent anatomical and experimental findings are discussed which show that neurons in the PVT provide divergent projections to subcortical regions that mediate defensive behaviors and that the projection to the NAcSh is critical for the enhanced social avoidance displayed in rats exposed to footshocks. A theoretical model is proposed for how the PVT integrates cortical and hypothalamic signals to modulate the behavioral responses associated with anxiety and other challenging situations.