Biology subjects

Perez, P. J.

Publications and source records attributed to Perez, P. J..

4 recordsLinked to original sources

bioRxiv2026

NPY+ Interneurons in Basolateral Amygdala are Activated by Aversive Stimuli

Traumatic events increase the risk for anxiety disorders, yet knowledge of how trauma modulates neuronal activity to induce anxiety is incomplete. The amygdala, which processes stressful sensory information, is enriched with interneurons that release the anxiolytic neurotransmitter neuropeptide Y (NPY). Amygdala NPY levels are reduced one week after an aversive event, suggesting chronic alteration of NPY+ interneurons; however, studies of in vivo amygdalar NPY+ cell activity during stressors are lacking. Here, we use a genetically encoded calcium sensor together with fiber photometry to investigate in vivo activation of NPY+ cells in basolateral amygdala (BLA) to aversive stimuli in mice. NPY+ cell activation was evaluated in response to two aversive stimuli, air puffs to the face (mild) and footshocks (strong). Air puffs caused a transient elevation of calcium in BLA NPY+ cells, indicating robust neuronal activation, in both male and female mice with no sex-dependent differences. Interestingly, there was habituation of the calcium signal in NPY+ cells to later air puff iterations. Strong footshocks also caused calcium elevation in both male and female mice with no sex-dependent differences. Excitingly, footshock induces a larger calcium response compared to air-puff. In contrast to air puff, the calcium signal to footshock was prolonged in later iterations. BLA NPY+ cell calcium signals were consistent in response to the same footshock protocol delivered 1 week later, indicating that activation of NPY+ cells by footshock is stable across this timeframe. Taken together, these results reveal a potential role for NPY+ interneurons in basolateral amygdala during aversive events.

neuroscience↗

bioRxiv2024

Modulation of Temporoammonic-CA1 Synapses by Neuropeptide Y is Through Y1 Receptors

The reduction of neuropeptide Y (NPY), an abundant neuromodulator in the brain, has been implicated in multiple neuropsychiatric disorders, such as depression and post-traumatic stress disorder (PTSD). The CA1 region of hippocampus is an important area for anxiety and highly expresses NPY. Injection of NPY into the CA1 is anxiolytic and has been shown to alleviate behavioral symptoms in a model of traumatic stress. It is known that activation of NPY Y1 receptors has anxiolytic effects and that NPYs anxiolytic effects in CA1 are blocked by an NPY Y1 receptor antagonist. However, the location of Y1 receptors mediating NPYs anxiolytic effects in CA1 is not yet known. CA1 receives inputs from entorhinal cortex through the temporammonic pathway (TA), which has been shown to be important for fear learning and sensitive to stress. Our lab previously showed that NPY reduces TA-evoked synaptic responses, however, the subtype of NPY receptor mediating this effect is not yet known. In this study, we show that Y1 receptors mediate the effects of both exogenous (bath-applied) and endogenously-released NPY in the TA pathway. This is the first demonstration of a Y1 receptor-mediated effect on synaptic function in CA1. Interestingly, chronic cell-type specific overexpression of NPY impairs the sensitivity of the TA pathway to NPY and the Y1 receptor agonist. However, the effect of NPY in the Schaffer collateral (SC) pathway, which is mediate by NPY Y2 receptors, is unaffected by NPY overexpression. There are pathway-specific differences in NPY receptors that modulate NPYs effects in CA1 and respond differently to NPY overexpression. Our results demonstrating that NPY acts at Y1 receptors in the TA pathway are consistent with the idea that the TA pathway underlies the anxiolytic effects of NPY in CA1.

neuroscience↗

bioRxiv2022

Probing different paradigms of morphine withdrawal on sleep behavior in male and female C57BL/6J mice

Opioid misuse has dramatically increased over the last few decades resulting in many people suffering from opioid use disorder (OUD). The prevalence of opioid overdose has been driven by the development of new synthetic opioids, increased availability of prescription opioids, and more recently, the COVID-19 pandemic. Coinciding with increases in exposure to opioids, the United States has also observed increases in multiple Narcan (naloxone) administrations as life-saving measures for respiratory depression, and, thus, consequently, naloxone-precipitated withdrawal. Sleep dysregulation is a main symptom of OUD and opioid withdrawal syndrome, and therefore, should be a key facet of animal models of OUD. Here we examine the effect of precipitated and spontaneous morphine withdrawal on sleep behaviors in C57BL/6J mice. We find that morphine administration and withdrawal dysregulate sleep, but not equally across morphine exposure paradigms. Furthermore, many environmental triggers promote relapse to drug-seeking/taking behavior, and the stress of disrupted sleep may fall into that category. We find that sleep deprivation dysregulates sleep in mice that had previous opioid withdrawal experience. Our data suggest that the 3-day precipitated withdrawal paradigm has the most profound effects on opioid-induced sleep dysregulation and further validates the construct of this model for opioid dependence and OUD. HighlightsO_LIMorphine withdrawal differentially dysregulates the sleep of male and female mice C_LIO_LI3-day precipitated withdrawal results in larger changes than spontaneous withdrawal C_LIO_LIOpioid withdrawal affects responses to future sleep deprivation differently between sexes C_LI

neuroscience↗

bioRxiv2019

Divergent behavioral responses in protracted opioid withdrawal in male and female C57BL/6J mice

Persons suffering from opioid use disorder (OUD) experience long-lasting dysphoric symptoms well into extended periods of withdrawal. This protracted withdrawal syndrome is notably characterized by heightened anxiety. Here we investigate if an exacerbated withdrawal model of acute morphine dependence results in lasting behavioral adaptation 6 weeks into forced abstinence. We found that our exacerbated morphine withdrawal paradigm produced distinct impairments in elevated-plus maze, open field, and social interaction tests in male and female mice. These findings will be relevant for future investigation examining the neural mechanisms underlying these behaviors, and will aid in uncovering physiological sex differences in response to opioid withdrawal.

neuroscience↗