Biology subjects

Derman, R. C.

Publications and source records attributed to Derman, R. C..

3 recordsLinked to original sources

bioRxiv2022

Persistent effects of acute trauma on Pavlovian-to-instrumental transfer

In humans, an acutely traumatic experience can lead to post-traumatic stress disorder (PTSD), which is often characterized by changes in anxiety and motivation months after trauma. There are few demonstrations of the persistent motivational effects of an acute stressor in rodent approaches to PTSD. In two experiments, we evaluated the persistent effects of a battery of footshocks in one context on appetitive Pavlovian conditioning, instrumental learning, and Pavlovian-to-instrumental transfer (PIT) in a different context. A battery of footshocks before appetitive training caused deficits in single-outcome PIT in male Long Evans rats. The same battery of footshocks after appetitive training, but before testing had little effect on single-outcome PIT, but there were some qualitative deficits. Although males showed more generalized fear from the aversive to the appetitive context compared to females, there were no effects of shock on sensory-specific PIT in male or female rats. In general females showed less evidence for sensory-specific PIT compared to males, who showed robust sensory-specific PIT, with clear extinction and spontaneous recovery of the sensory-specific PIT effect across test sessions. These findings show that (a) an acute trauma can have persistent effects on general motivational processes and (b) sensory-specific PIT is a useful approach for exploring sex differences in strategies for instrumental learning. We discuss implications for current approaches to stress and motivation in preclinical and clinical studies.

neuroscience↗

bioRxiv2019

Effects of hM4Di activation in CamKII basolateral amygdala neurons and CNO treatment on Sensory-Specific vs. General-PIT; refining PIT circuits and considerations for using CNO.

Pavlovian stimuli can influence instrumental behaviors, a phenomenon known as Pavlovian-to-instrumental transfer (PIT). PIT arises via psychologically and neurobiologically independent processes as Sensory-Specific-PIT (SS-PIT) and General-PIT. SS-, but not General-PIT, relies on the basolateral amygdala (BLA), however the specific BLA neuronal populations involved are unknown. Therefore, here we determined the contribution of glutamatergic BLA neurons to SS-PIT. The BLA was transduced with virus containing either GFP or hM4Di, driven by the CamKII promoter. Rats were then tested for SS- and General-PIT following Vehicle or Clozapine-n-oxide (CNO, the hM4Di-activating ligand) injection. CNO had no effect on SS-PIT in the GFP control group, but selectively blocked its expression in the hM4Di-expressing group. Furthermore, CNO did not alter the expression of Pavlovian outcome devaluation effects in GFP or hM4Di expressing groups, indicating that the hM4Di-mediated loss of SS-PIT did not result from an inability to recall the sensory-specific details of the Pavlovian stimulus-outcome associations. Unexpectedly, CNO disrupted General-PIT in both GFP and hM4Di expressing groups, indicating that CNO alone is sufficient to disrupt affective, but not sensory-specific processes. Disruption of General-PIT by CNO was not due to generalized motor effects, but instead may be related to shifts in internal state produced by CNO. Together these data identify BLA CamKII neurons as critical for the expression of SS-PIT, and reveal important considerations for using CNO to study general affective motivation.

neuroscience↗

bioRxiv2019

Affective Pavlovian motivation is enhanced in obesity susceptible populations; implications for incentive motivation in obesity

Global obesity rates continue to rise, presenting a major challenge to human health. Efforts to uncover the drivers of this epidemic have highlighted the contribution of Pavlovian motivational processes to overeating. In humans, brain and behavioral reactivity to food related stimuli positively correlates with subsequent weight gain. In concordance with this, selectively bred obesity-prone rats exhibit stronger cue-triggered food-seeking via single outcome Pavlovian-to-instrumental transfer (SO PIT) than obesity-resistant rats. These data show that Pavlovian motivation is stronger in selectively bred obesity-prone groups. However, whether obesity susceptibility in outbred populations is associated with enhanced PIT is unknown. Moreover, PIT can arise via two neurobehaviorally dissociable processes, a sensory specific versus a general affective process that cannot be distinguished by SO PIT. Thus, it is unclear which PIT process is enhanced in obesity-prone groups. Therefore, we determined whether obesity susceptibility in outbred populations is associated with enhanced Sensory Specific (SS) PIT or General PIT and whether expression of these forms of PIT differs between selectively bred obesity-prone versus obesity-resistant rats. We find that in outbred rats, the magnitude of General PIT is positively correlated with subsequently determined obesity susceptibility. In selectively bred rats, the magnitude of General PIT was stronger in obesity-prone versus obesity-resistant groups. Jointly, these data show that enhanced affective Pavlovian motivation is tightly linked to obesity vulnerability, supporting a role for phenotypic differences in incentive motivation for the development of obesity. This has important implications for obesity prevention and for understanding the neurocircuitry mediating enhanced food-seeking in vulnerable individuals.

animal behavior and cognition↗