Biology subjects

Flores, R. J.

Publications and source records attributed to Flores, R. J..

5 recordsLinked to original sources

bioRxiv2025

Neuropeptidergic transmission shapes emergent properties of prefrontal cortical circuits underlying learning

The prefrontal cortex (PFC) is essential for top-down control of affect and its dysfunction is implicated in many psychiatric disorders. Inhibitory interneurons expressing somatostatin have been implicated in cognition, affect, and disease. However, somatostatins function as a neuropeptide transmitter remains unclear. Here, we investigated the contribution of somatostatin neurotransmission in differentiating between salient (rewarding or aversive) and neutral outcomes. Monitoring somatostatin release and somatostatin receptor antagonism revealed time-dependent regulation of outcome-specific associative learning during acquisition. We found that somatostatin transmission enables configural representations incorporating a salient, aversive outcome in prefrontal cortical neurons, and a threat-driven shift in population-level network activity in-vivo. These findings show a novel role for somatostatin, an interneuron "cellular marker", signaling in shaping learning and emergent network dynamics. Further this framework revealed that reduced somatostatin neuropeptidergic transmission may impair top-down control of affective behaviors observed in mental health disorders, suggesting potential new avenues for therapeutic intervention.

neuroscience↗

bioRxiv2024

Prefrontal cortical dynorphin peptidergic transmission constrains threat-driven behavioral and network states

Prefrontal cortical (PFC) circuits provide top-down control of threat reactivity. This includes ventromedial PFC (vmPFC) circuitry, which plays a role in suppressing fear-related behavioral states. Dynorphin (Dyn) has been implicated in mediating negative affect and mal-adaptive behaviors induced by severe threats and is expressed in limbic circuits, including the vmPFC. However, there is a critical knowledge gap in our understanding of how vmPFC Dyn-expressing neurons and Dyn transmission detect threats and regulate expression of defensive behaviors. Here, we demonstrate that Dyn cells are broadly activated by threats and release Dyn locally in the vmPFC to limit passive defensive behaviors. We further demonstrate that vmPFC Dyn-mediated signaling promotes a switch of vmPFC networks to a fear-related state. In conclusion, we reveal a previously unknown role of vmPFC Dyn neurons and Dyn neuropeptidergic transmission in suppressing defensive behaviors in response to threats via state-driven changes in vmPFC networks. Highlights[bullet] vmPFCDyn neurons are activated by threats and threat-predictive cues [bullet]Characterization of a genetically-encoded kappa-opioid receptor sensor [bullet]vmPFCDyn neurons rapidly release Dyn in response to threats and their predictors [bullet]vmPFCDyn signaling opposes threat-induced passive defensive behaviors [bullet]Dyn signaling promotes threat-evoked state transitions in vmPFC networks

neuroscience↗

bioRxiv2023

Dissociable control of motivation and reinforcement by distinct ventral striatal dopamine receptors

Dopamine release in striatal circuits, including the nucleus accumbens (NAc), tracks separable features of reward such as motivation and reinforcement. However, the cellular and circuit mechanisms by which dopamine receptors transform dopamine release into distinct constructs of reward remain unclear. Here, we show that dopamine D3 receptor (D3R) signaling in the NAc drives motivated behavior by regulating local NAc microcircuits. Furthermore, D3Rs co-express with dopamine D1 receptors (D1Rs), which regulate reinforcement, but not motivation. Paralleling dissociable roles in reward function, we report non-overlapping physiological actions of D3R and D1R signaling in NAc neurons. Our results establish a novel cellular framework wherein dopamine signaling within the same NAc cell type is physiologically compartmentalized via actions on distinct dopamine receptors. This structural and functional organization provides neurons in a limbic circuit with the unique ability to orchestrate dissociable aspects of reward-related behaviors that are relevant to the etiology of neuropsychiatric disorders.

neuroscience↗

bioRxiv2019

Exposure to nicotine vapor causes short-term increases in impulsive choice in rats.

BackgroundPrevious studies have shown that exposure to nicotine smoke increases impulsivity. Surprisingly, research investigating the effects of electronic cigarette nicotine vapor exposure on impulsivity has not been conducted. Therefore, the present study examined the effects of nicotine vapor exposure on impulsive choice. MethodsTwenty-four adult male rats were trained in the delay discounting task to choose between small immediate food rewards or larger food rewards with delayed deliveries. After 24 days of training in the delay discounting task, rats were passively exposed to vapor containing either 0, 12, or 24 mg/mL of nicotine for 10 days. To monitor exposure to nicotine, serum cotinine levels were assessed on exposure days 1, 5, and 10 using enzyme-linked immunosorbent assay (ELISA). Following vapor exposure, rats were retrained in the delay discounting task until stable performance was achieved, and the effects of nicotine vapor exposure on choice preference were assessed. ResultsRats that were exposed to 12 and 24 mg/mL nicotine vapor displayed higher serum cotinine levels, relative to those exposed to 0 mg/mL nicotine vapor. There were no differences in impulsive choice between any of the vapor groups when tested 15-21 days after exposure. However, increases in impulsive choice were observed when testing immediately following exposure to 24 mg/mL nicotine vapor, relative to immediately following exposure to 0 mg/mL nicotine vapor. ConclusionsFindings suggest that while exposure to nicotine vapor may not cause long-term changes in decision making, it can cause short-term increases in impulsive choice, an effect that can have negative social and health consequences.

animal behavior and cognition↗

bioRxiv2019

Estradiol promotes and progesterone reduces anxiety-like behavior produced by nicotine withdrawal in rats

The present study assessed sex differences and the role of ovarian hormones in the behavioral effects of nicotine withdrawal. Study 1 compared physical signs, anxiety-like behavior, and corticosterone levels in male, intact female, and ovariectomized (OVX) female rats during nicotine withdrawal. Estradiol (E2) and progesterone levels were also assessed in intact females that were tested during different phases of the 4-day estrous cycle. Study 2 assessed the role of ovarian hormones in withdrawal by comparing the same measures in OVX rats that received vehicle, E2, or E2+progesterone prior to testing. Briefly, rats received a sham surgery or an ovariectomy procedure. Fifteen days later, rats were prepared with a pump that delivered nicotine for 14 days. On the test day, rats received saline or the nicotinic receptor antagonist, mecamylamine to precipitate withdrawal. Physical signs and anxiety-like behavior were assessed on the elevated plus maze (EPM) and light-dark transfer (LDT) tests. During withdrawal, intact females displayed greater anxiety-like behavior and corticosterone levels as compared to male and OVX rats. Females tested in estrus (when E2 is relatively low) displayed less anxiety-like behavior and corticosterone versus all other phases. Anxiety-like behavior and corticosterone were positively correlated with E2 and negatively correlated with progesterone. Intact females displaying high E2/low progesterone displayed greater anxiety-like behavior and corticosterone as compared to females displaying low E2/high progesterone. Lastly, OVX-E2 rats displayed greater anxiety-like behavior than OVX-E2+progesterone rat. These data suggest that E2 promotes and progesterone reduces anxiety-like behavior produced by withdrawal.

animal behavior and cognition↗