Paraventricular Thalamus Controls Behavior during Motivational Conflict

Abstract

Decision-making often involves motivational conflict because of the competing demands of approach and avoidance for a common resource: behavior. This conflict must be resolved as a necessary precursor for adaptive behavior. Here we show a role for the paraventricular thalamus (PVT) in behavioral control during motivational conflict. We used Pavlovian counterconditioning in male rats to establish a conditioned stimulus (CS) as a signal for reward (or danger) and then transformed the same CS into a signal for danger (or reward). After such training, the CS controls conflicting appetitive and aversive behaviors. To assess PVT involvement in conflict, we injected an adeno-associated virus (AAV) expressing the genetically encoded Ca 2ϩ indicator GCaMP and used fiber photometry to record population PVT Ca 2ϩ signals. We show distinct profiles of responsivity across the anterior-posterior axis of PVT during conflict, including an ordinal relationship between posterior PVT CS responses and behavior strength. To study the causal role of PVT in behavioral control during conflict, we injected AAV expressing the inhibitory hM4Di DREADD and determined the effects of chemogenetic PVT inhibition on behavior. We show that chemogenetic inhibition across the anterior-posterior axis of the PVT, but not anterior or posterior PVT alone, disrupts arbitration between appetitive and aversive behaviors when they are in conflict but has no effect when these behaviors are assessed in isolation. Together, our findings identify PVT as central to behavioral control during motivational conflict.

Analyzing Event-Related Transients: Confidence Intervals, Permutation Tests, and Consecutive Thresholds

“…emulate subject-based analysis, a subject population for each condition (n = 1,000; Figures 2A,B) was generated by randomly sampling and averaging 1-31 lines from their respective activity populations. These parameters correspond approximately to data generated by fiber photometry recordings (Sengupta et al, 2018;Choi et al, 2019).…”

“…For example, what kind of analysis is appropriate and how to effectively control the Type I error (false positive) rate whilst still achieving sufficient statistical power? Here we consider two straightforward alternatives to the use of summary statistics when analyzing fiber photometry data: (1) confidence intervals (CIs) around the peri-event dF waveform (e.g., Choi et al, 2019); and (2) permutation tests across the peri-event window (e.g., Pascoli et al, 2018).…”

The Paraventricular Thalamus is a Critical Mediator of Top-down Control of Cue-motivated Behavior in Rats

“…For these studies, the effects of PrL-PVT manipulation were examined early in Pavlovian training, when Pavlovian cues are known to evoke a DA response in the NAc to a different degree in STs and GTs 28,56 . Although we expected to observe more robust behavioral effects during this period, we found that stimulation of the PrL-PVT pathway early in Pavlovian training did not affect the behavior of STs, nor did it significantly affect extracellular It has become increasingly apparent in recent years that the PVT and its associated circuitry play an important role in motivated behaviors, including those related to addiction and anxiety-related disorders 16,33,[57][58][59][60][61][62][63][64][65][66][67][68] . Here, we honed in on the PrL-PVT pathway and exploited an animal model of individual differences in cue-reward learning to demonstrate that this circuit acts as a top-down control mechanism to suppress the attribution of incentive value to a food-paired cue.…”

From Isolated Emotional Memories to Their Competition During Conflict

“…A currently popular notion of PFC suggests its key role in emotional processing and decision making (Damasio, 1996;Miller and Cohen, 2001) which often depends on weighing information about aversion and reward memories to control behavior. The PFC may exert its conflict resolution function through connections with other structures, such as the striatum (Berendse et al, 1992), thalamus (Choi et al, 2019), ventral hippocampus (Schumacher et al, 2018) and amygdala (McDonald et al, 1996;Gabbott et al, 2005), to name a few. A broad range of studies has shown that medial PFC (mPFC) encodes both rewarding (Otis et al, 2015) and aversive stimuli (Burgos-Robles et al, 2009).…”

“…This involves considering the weights of each emotional memory because animals choose what behavior to execute guided by the relative weighs of opposing memories. Both early and recent works have made efforts to characterize approach-avoidance conflict (Miller, 1944;Choi and Kim, 2010;Friedman et al, 2015;Burgos-Robles et al, 2017;Schumacher et al, 2018;Choi et al, 2019;Verharen et al, 2019;Walters et al, 2019). We recently developed two related approach-avoidance conflict animal models that are set to separate discrete variables (reward memory retrieval, threat memory retrieval and their competition) in the same individual by putting variable weigh on reward-or threat-related memories through training, and therefore are amenable to study both sides of the coin: when reward has higher relative value than threat and vice versa.…”