Punishment history biases corticothalamic responses to motivationally-significant stimuli

Abstract

Making predictions about future rewards or pun-1 ishments is fundamental to adaptive behavior. 2 These processes are influenced by prior experi-3 ence. For example, prior exposure to aversive 4 stimuli or stressors changes behavioral responses 5 to negative-and positive-value predictive cues.6Here, we demonstrate a role for medial pre-7 frontal cortex (mPFC) neurons projecting to the 8 paraventricular nucleus of the thalamus (PVT; 9 mPFC→PVT) in this process. We found that a 10 history of punishments negatively biased behav-11 ioral responses to motivationally-relevant stim-12 uli in mice and that this negative bias was asso-13 ciated with hyperactivity in mPFC→PVT neu-14 rons during exposure to those cues. Further-15 more, artificially mimicking this hyperactive re-16 sponse with selective optogenetic excitation of 17 the same pathway recapitulated the punishment-18 induced negative behavioral bias. Together, our 19 results highlight how information flow within the 20 mPFC→PVT circuit is critical for making pre-21 dictions about imminent motivationally-relevant 22 outcomes as a function of prior experience. 23 vated by multiple forms of stressors (Chastrette et al., 75 1991; Sharp et al., 1991; Cullinan et al., 1995; Bubser 76 and Deutch, 1999; Spencer et al., 2004) and coordinate 77 behavioral responses to stress (Hsu et al., 2014; Do-78 Monte et al., 2015; Penzo et al., 2015; Zhu et al., 2016; 79 Do-Monte et al., 2017; Beas et al., 2018). On the other 80 hand, under conditions of opposing emotional valence, 81 PVT plays a role in multiple forms of stimulus-reward 82 learning and PVT neurons have been reported to show 83 reward-modulated responses (Schiltz et al., 2005; Igel-84 strom et al. , 2010; Martin-Fardon and Boutrel, 2012; 85 James and Dayas, 2013; Browning et al., 2014; Haight 86 and Flagel, 2014; Li et al., 2016; Choi et al., 2019). 87Activity in mPFC neurons projecting to the PVT also 88 suppresses both the acquisition and expression of condi-89 tioned reward seeking (Otis et al., 2017). 90Taken together, these studies place the mPFC to PVT 91 projection in a unique position to integrate information 92 about positive and negative motivationally-relevant cues 93 and translate it into adaptive behavioral responses. How 94 these projection-specific prefrontal neurons regulate be-95 115 phase, four odor cues (A, B, C and D, counterbalanced) 116 were presented. Odor A predicted an appetitive sweet 117 solution (3 µl of 5% sucrose water). Odor B predicted 118 an aversive bitter solution (3 µl of 10 mM denatonium 119 water). Odor C was associated with no reinforcement. 120 Odor D predicted a punishment (an unavoidable air puff 121 delivered to the mouse's right eye) in mice assigned to 122 the air puff group and was associated with no reinforce-123 ment in mice assigned to the no air puff group. Each 124 behavioral trial began with an odor (1 s; conditioned 125 stimulus, CS), followed by a 1-s delay and an outcome 126 (unconditioned stimulus, US). Mice showed essentially 127 binary respo...

Anterior Cingulate Cortex and the Control of Dynamic Behavior in Primates

“…Third, rodent studies mirror our findings of valence specificity in mPFC [136]. And last, consistent with our proposal in Figure 4, the Stuber laboratory [137] recently provided evidence that neurons with distinct value or outcome coding strategies project to distinct subcortical targets (see also [138]). Given such mounting data, additional experiments are now required to assess the functional similarities and differences across species at the neuronal level.…”

Functional Connectivity of the Human Paraventricular Thalamic Nucleus: Insights From High Field Functional MRI

“…Indeed, the posterior PVT has recently been referred to as both a potential ''stressmemory'' center of the brain (Bhatnagar and Dallman, 1998;Bhatnagar et al, 2000;Fenoglio et al, 2006;Heydendael et al, 2011) and the whole nucleus as the ''traffic light of motivated behaviors'' (McGinty and Otis, 2020). The past decade has seen multiple review articles and commentaries describing the heterogeneity of PVT anatomy, diverse neurochemistry, and functions (James and Dayas, 2013;Do-Monte and Kirouac, 2017;Millan et al, 2017;Barson et al, 2020), including a potential role in long-term fear memory (Padilla-Coreano et al, 2012;Penzo et al, 2015;Do-Monte et al, 2016), salience, conflict resolution (Choi and McNally, 2017;Choi et al, 2019), motivated memory, and associated behaviors (Kirouac, 2015;Millan et al, 2017;Zhu et al, 2018;Zhou and Zhu, 2019;Lucantonio et al, 2020). However, given its small size [e.g., ∼7 mm 3 for left paraventricular nucleus (Krauth et al, 2010;Jo et al, 2019)], there is a dearth in our understanding of PVT function in the human brain.…”

A ventrolateral medulla-midline thalamic circuit for hypoglycemic feeding

“…For example, orexinergic input to the PVT may carry arousal-related signals that invigorate reward-seeking behavior 12,58 . In contrast, inputs relaying information about threatening situations may dampen PVT responding to reward-related cues resulting in diminished food seeking 43,59,60 . This view is supported by recent studies suggesting that the PVT is required amid motivational conflicts for the integration of reward-and aversive-related guiding behavior 42,43 .…”