Biology subjects

Ferrario, C.

Publications and source records attributed to Ferrario, C..

4 recordsLinked to original sources

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

Effects of the estrous cycle and ovarian hormones on cue-triggered motivation and intrinsic excitability of medium spiny neurons in the Nucleus Accumbens of female rats

Naturally occurring alterations in estradiol influence food intake in females. However, how motivational responses to food cues are affected by the estrous cycle or ovarian hormones is unknown. In addition, while individual susceptibility to obesity is accompanied by enhanced incentive motivational responses to food cues and increased NAc intrinsic excitability in males, studies in females are absent. Here, we examined basal differences in intrinsic NAc excitability of obesity-prone vs. obesity-resistant females and determined how conditioned approach (a measure of cue-triggered motivation), food intake, and motivation for food vary with the cycle in naturally cycling female obesity-prone, obesity-resistant, and outbred Sprague-Dawley rats. Finally, we used ovariectomy followed by hormone treatment to determine the role of ovarian hormones in cue-triggered motivation in selectively-bred and outbred female rats. We found that intrinsic excitability of NAc MSNs and conditioned approach are enhanced in female obesity-prone vs. obesity-resistant rats. These effects were driven by greater MSN excitability and conditioned approach behavior during metestrus/diestrus vs. proestrus/estrus in obesity-prone but not obesity-resistant rats, despite similar regulation of food intake and food motivation by the cycle in these groups. Furthermore, estradiol and progesterone treatment reduced conditioned approach behavior in obesity-prone and outbred Sprague-Dawley females. To our knowledge, these data are the first to demonstrate cycle- and hormone-dependent effects on the motivational response to a food cue, and the only studies to date to determine how individual susceptibility to obesity influences NAc excitability, cue-triggered food-seeking, and differences in the regulation of these neurobehavioral responses by the cycle.

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↗

bioRxiv2019

Insulin enhances presynaptic glutamate release in the nucleus accumbens via opioid receptor-mediated disinhibition

Insulin influences activity in brain centers that mediate reward and motivation in humans. However, nothing is known about how insulin influences excitatory transmission in regions like the nucleus accumbens (NAc), which governs motivational processes in the adult brain. Further, insulin dysregulation that accompanies obesity is linked to cognitive decline, depression, anxiety, and aberrant motivation that also rely on NAc excitatory transmission. Using a combination of whole-cell patch clamp and biochemical approaches we determined how insulin affects NAc glutamatergic transmission. We show that insulin receptor activation increases presynaptic glutamate release via a previously unidentified form of opioid receptor-mediated disinhibition. In contrast, activation of IGF receptors by insulin decreases presynaptic glutamate release in adult male rats. Furthermore, obesity results in a loss of insulin receptor-mediated increases and a reduction in NAc insulin receptor surface expression, while preserving reductions in transmission mediated by IGRFs. These results provide the first insights into how insulin influences excitatory transmission in the adult brain, they provide foundational information about opioid-mediated regulation of NAc glutamatergic transmission, and have broad implications for the regulation of motivation and reward related processes by peripheral hormones.

neuroscience↗