The Paraventricular Nucleus of the Thalamus as an Integrating and Relay Node in the Brain Anxiety Network

Abstract

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.

Extinction blunts paraventricular thalamic contributions to heroin relapse

“…Moreover, the PVT→NAc pathway mediates withdrawal signs in morphine-dependent mice ( Zhu et al, 2016 ) and is necessary for retrieval of opioid-associated memories ( Keyes et al, 2020 ). These data support previous findings implicating the PVT in aversive states ( Kirouac, 2015 , 2021 ; Li et al, 2011 ; Yasoshima et al, 2007 ), and they identify a specific output (to NAc) by which the PVT mediates aversion and morphine-associated memories ( Keyes et al, 2020 ; Zhu et al, 2016 ).…”

Extensive divergence of projections to the forebrain from neurons in the paraventricular nucleus of the thalamus

“…PVT neurons have been shown to be responsive to appetitive conditions and the cues that predict their occurrences (for more details see reviews by Zhou and Zhu 2019 ; Barson et al 2020 ; Kirouac 2015 , 2021 ; Millan et al 2017 ; McGinty and Otis 2020 ). While a number of studies have employed single unit recording or calcium imaging to examine if PVT neurons respond to appetitive and aversive stimuli (reviewed in McGinty and Otis 2020 ; Barson et al 2020 ), most studies have not made comparisons between the aPVT and pPVT or whether the same neuron responds to both emotional valences.…”

“…Results from anatomical studies led to the refinement of this hypothesis by proposing that individual members of this group of thalamic nuclei were associated with specialized cortical-subcortical circuits (Alexander et al 1990 ; Groenewegen and Berendse 1994 ). Interest in the PVT has noticeably increased with the recognition that this nucleus sends dense projections to subcortical regions important for the regulation of emotional and motivational behavior (details of the anatomy of the PVT are reviewed in Kirouac 2015 , 2021 ). The areas of the forebrain most densely innervated by the PVT include 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) (Dong et al 2017 ; Vertes and Hoover 2008 ; Li and Kirouac 2008 ).…”

Thalamo-Nucleus Accumbens Projections in Motivated Behaviors and Addiction

“…Given the important role of the NAc in motivated behaviors and the relevance of the PVT in negative emotional behaviors (Hsu et al, 2014;Kirouac, 2021), several groups have tried to assess the motivational valence of the PVT-NAc pathway (PVT = > NAc) (Table 1). In a real-time place preference assay (RTPP), mice seemed to reduce the time spent in the chamber associated with the optogenetic stimulation of PVT = > NAc shell (Zhu et al, 2016;Do-Monte et al, 2017).…”