Biology subjects

Campus, P.

Publications and source records attributed to Campus, P..

6 recordsLinked to original sources

bioRxiv2026

Chemogenetic Inhibition of Lateral Hypothalamus Inputs to the Paraventricular Thalamus Reduces Goal-Tracking in a Behaviorally Flexible Subgroup of Male Rats

The paraventricular nucleus of the thalamus (PVT) has emerged as an important node in circuits regulating motivated behavior. The neuronal pathway from the lateral hypothalamus (LH) to the PVT has specifically been shown to regulate arousal, feeding, and reward seeking. However, the involvement of the LH-PVT pathway in individual differences in cue-motivated behavior remains unclear. During a Pavlovian conditioned approach paradigm, when a reward is repeatedly preceded by the presentation of a cue, rats come to exhibit a conditioned response to the cue. One extreme of the population, sign-trackers (STs), approach and interact with the cue itself; while the other extreme, goal-trackers (GTs), approach the location of reward delivery. Intermediate responders (IRs) approach and interact with both the cue and reward location, without a clear preference. We utilized a Pavlovian conditioned approach paradigm to examine the effects of LH-PVT pathway inhibition on individual differences in cue-motivated behavior. A dual-vector approach was used to selectively express inhibitory chemogenetic receptors in the LH-PVT pathway. We found that inhibition of the LH-PVT pathway selectively attenuates the expression of goal-tracking behavior, without affecting sign-tracking. This effect is driven primarily by IR rats, as inhibition of LH-PVT neurons attenuates goal-tracking behavior in IRs, without impacting the response of STs or GTs. We speculate that the flexibility of responding in IR rats made them especially vulnerable to this manipulation. These findings identify the LH-PVT pathway as a selective contributor to reward-directed conditioned responding and a circuit substrate for behavioral flexibility. Significance StatementIndividuals differ in how reward-predictive cues motivate behavior, a feature linked to vulnerability and resilience to maladaptive reward seeking. The paraventricular thalamus (PVT), a midline hub with broad limbic connectivity, and its input from the lateral hypothalamus (LH) influences arousal, feeding, and reward seeking, but the role of the LH-PVT pathway in individual variability in cue-motivated behavior is unclear. We used chemogenetics to selectively suppress LH-PVT neurons during a Pavlovian conditioned approach paradigm. Inhibiting this projection reduced goal-tracking without altering sign-tracking, and this effect was driven primarily by intermediate responders, a phenotype characterized by behavioral flexibility. These results implicate LH-PVT signaling in reward-directed conditioned responding and suggest that this pathway contributes to flexible cue-motivated behavior.

neuroscience↗

bioRxiv2023

Inhibition of dopamine neurons prevents incentive value encoding of a reward cue:With revelations from deep phenotyping

The survival of an organism is dependent on their ability to respond to cues in the environment. Such cues can attain control over behavior as a function of the value ascribed to them. Some individuals have an inherent tendency to attribute reward-paired cues with incentive motivational value, or incentive salience. For these individuals, termed sign-trackers, a discrete cue that precedes reward delivery becomes attractive and desirable in its own right. Prior work suggests that the behavior of sign-trackers is dopamine-dependent, and cue-elicited dopamine in the nucleus accumbens is believed to encode the incentive value of reward cues. Here we exploited the temporal resolution of optogenetics to determine whether selective inhibition of ventral tegmental area (VTA) dopamine neurons during cue presentation attenuates the propensity to sign-track. Using male tyrosine hydroxylase (TH)-Cre Long Evans rats it was found that, under baseline conditions, [~]84% of TH-Cre rats tend to sign-track. Laser-induced inhibition of VTA dopamine neurons during cue presentation prevented the development of sign-tracking behavior, without affecting goal-tracking behavior. When laser inhibition was terminated, these same rats developed a sign-tracking response. Video analysis using DeepLabCut revealed that, relative to rats that received laser inhibition, rats in the control group spent more time near the location of the reward cue even when it was not present and were more likely to orient towards and approach the cue during its presentation. These findings demonstrate that cue-elicited dopamine release is critical for the attribution of incentive salience to reward cues. Significance StatementActivity of dopamine neurons in the ventral tegmental area (VTA) during cue presentation is necessary for the development of a sign-tracking, but not a goal-tracking, conditioned response in a Pavlovian task. We capitalized on the temporal precision of optogenetics to pair cue presentation with inhibition of VTA dopamine neurons. A detailed behavioral analysis with DeepLabCut revealed that cue-directed behaviors do not emerge without VTA dopamine. Importantly, however, when optogenetic inhibition is lifted, cue-directed behaviors increase, and a sign-tracking response develops. These findings confirm the necessity of VTA dopamine during cue presentation to encode the incentive value of reward cues.

neuroscience↗

bioRxiv2020

Neuroendocrine and behavioral measures of negative valence in male sign-tracker and goal-tracker rats

Environmental cues attain the ability to guide behavior via learned associations. As predictors, cues can elicit adaptive behavior and lead to valuable resources (e.g., food). For some individuals, however, cues are transformed into incentive stimuli and elicit motivational states that can be maladaptive. The goal-tracker/sign-tracker animal model captures individual differences in cue-motivated behaviors, with reward-associated cues serving as predictors of reward for both phenotypes but becoming incentive stimuli to a greater degree for sign-trackers. While these distinct phenotypes are characterized based on Pavlovian conditioned approach behavior, they exhibit differences on a number of behaviors relevant to psychopathology. To further characterize the neurobehavioral endophenotype associated with individual differences in cue-reward learning, neuroendocrine and behavioral profiles associated with stress and anxiety were investigated in male goal-tracker, sign-tracker, and intermediate responder rats. It was revealed that baseline corticosterone increases with Pavlovian learning, but to the same degree, regardless of phenotype. No significant differences in behavior were observed between goaltrackers and sign-trackers during an elevated plus maze or open field test, nor were there differences in corticosterone response to the open field test or physiological restraint. Upon examination of central markers associated with stress-reactivity, we found that sign-trackers have greater glucocorticoid receptor mRNA expression in the ventral hippocampus, with no phenotypic differences in the dorsal hippocampus or prelimbic cortex. These findings demonstrate that goal-trackers and sign-trackers do not differ on stress- and anxiety-related behaviors, and suggest that differences in neuroendocrine measures between these phenotypes can be attributed to distinct cue-reward learning styles. Significance StatementWhile the goal-tracker/ sign-tracker animal model derives from individual differences in Pavlovian conditioned approach behavior, other traits, including some of relevance to addiction and post-traumatic stress disorder, have been shown to co-exist with the propensity to sign-track. The extent to which this model encompasses differences in aversive arousal and associated neuroendocrine measures, however, remains largely unexplored. Here we show that behavioral and corticosterone response to stress-related paradigms do not differ between goal-trackers and sign-trackers. However, glucocorticoid receptor expression in the ventral hippocampus does differ between phenotypes, suggesting that this central marker that is typically associated with stress-responsivity, may, in fact, play an important role in appetitive motivation.

animal behavior and cognition↗

bioRxiv2020

The lateral hypothalamus and orexinergic transmission in the paraventricular thalamus promote the attribution of incentive salience to reward-associated cues

RationalePrior research suggests that inputs from the lateral hypothalamic area (LHA) to the paraventricular nucleus of the thalamus (PVT) contribute to the attribution of incentive salience to Pavlovian-conditioned reward cues. However, a causal role for the LHA in this phenomenon has not been demonstrated. In addition, it is unknown which hypothalamic neurotransmitter or peptide system(s) are involved in mediating incentive salience attribution. ObjectivesTo examine: 1) the role of the LHA in the propensity to attribute incentive salience to reward cues, and 2) the role of orexinergic signaling in the PVT on the expression of Pavlovian conditioned approach (PavCA) behavior, a reflection of incentive salience attribution. MethodsMale Sprague-Dawley rats received bilateral excitotoxic lesions of the LHA prior to the acquisition of Pavlovian conditioned approach (PavCA) behavior. A separate cohort of male rats acquired PavCA behavior and were characterized as sign-trackers (STs) or goal-trackers (GTs) based on their conditioned response. The orexin 1 receptor (OX1r) antagonist SB-334867, or the orexin 2 receptor (OX2r) antagonist TCS-OX2-29, were then administered directly into the PVT to assess the effects of these pharmacological agents on the expression of PavCA behavior and on the conditioned reinforcing properties of the Pavlovian reward cue. ResultsLesions of the LHA before training attenuated the development of lever-directed (sign-tracking) behaviors in the PavCA paradigm, without affecting magazine-directed (goal-tracking) behaviors. In STs, administration of the OX1r antagonist into the PVT reduced lever-directed behaviors and increased magazine-directed behaviors; while administration of the OX2r antagonist only reduced lever-directed behaviors. Further, OX2r, but not OX1r, antagonism was able to reduce the incentive motivational value of the conditioned stimulus on a conditioned reinforcement test in STs. The behavior of GTs was unaffected by orexinergic antagonism in the PVT. ConclusionsThe LHA is necessary for the attribution of incentive salience to reward cues and, thereby, the development of a sign-tracking conditioned response. Furthermore, blockade of orexin signaling in the PVT attenuates the incentive value of a Pavlovian reward cue. These data suggest that hypothalamic orexin inputs to the PVT are a key component of the circuitry that encodes the incentive motivational value of reward cues and promotes maladaptive cue-driven behaviors.

neuroscience↗

bioRxiv2020

Inhibition of a cortico-thalamic circuit attenuates cue-induced reinstatement of drug-seeking behavior in relapse prone rats

Relapse often occurs when individuals are exposed to stimuli or cues previously associated with the drug-taking experience. The ability of drug cues to trigger relapse is believed to be a consequence of incentive salience attribution, a process by which the incentive value of reward is transferred to the reward-paired cue. Sign-tracker (ST) rats that attribute enhanced incentive value to reward cues are more prone to relapse compared to goal-tracker (GT) rats that primarily attribute predictive value to such cues. The neurobiological mechanisms underlying this individual variation in relapse propensity remains largely unexplored. The paraventricular nucleus of the thalamus (PVT) has been identified as a critical node in the regulation of cue-elicited behaviors in STs and GTs, including cue-induced reinstatement of drug-seeking behavior. Here we used a chemogenetic approach to assess whether "top-down" cortical input from the prelimbic cortex (PrL) to the PVT plays a role in mediating individual differences in relapse propensity. Chemogenetic inhibition of the PrL-PVT pathway selectively decreased cue-induced reinstatement of drug-seeking behavior in STs, without affecting behavior in GTs. In contrast, cocaine-primed drug-seeking behavior was not affected in either phenotype. Furthermore, when rats were characterized based on a different behavioral phenotype - locomotor response to novelty - inhibition of the PrL-PVT pathway had no effect on either cue- or drug-induced reinstatement. These results highlight an important role for the PrL-PVT pathway in vulnerability to relapse that is driven by individual differences in the propensity to attribute incentive salience to discrete reward cues.

neuroscience↗

bioRxiv2019

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

Cues in the environment can elicit complex emotional states, and thereby maladaptive behavior, as a function of their ascribed value. Here we capture individual variation in the propensity to attribute motivational value to reward-cues using the sign-tracker/goal-tracker animal model. Goal-trackers attribute predictive value to reward-cues, and sign-trackers attribute both predictive and incentive value. Using chemogenetics and microdialysis, we show that, in sign-trackers, stimulation of the neuronal pathway from the prelimbic cortex (PrL) to the paraventricular nucleus of the thalamus (PVT) decreases the incentive value of a reward-cue. In contrast, in goal-trackers, inhibition of the PrL-PVT pathway increases both the incentive value and dopamine levels in the nucleus accumbens shell. The PrL-PVT pathway, therefore, exerts top-down control over the dopamine-dependent process of incentive salience attribution. These results highlight PrL-PVT pathway as a potential target for treating psychopathologies associated with the attribution of excessive incentive value to reward-cues, including addiction.

neuroscience↗