Biology subjects

Ritchie, J. L.

Publications and source records attributed to Ritchie, J. L..

4 recordsLinked to original sources

bioRxiv2025

Adolescent alcohol exposure disrupts extinction learning and retrosplenial cortex physiology in adult males

Adolescent binge drinking can lead to a myriad of issues in adulthood, including psychiatric comorbidities that worsen clinical prognosis. Efforts to understand the effects of adolescent alcohol exposure on later health outcomes have unveiled lasting effects on physiology of brain regions critical for associative learning processes, including the hippocampus and prefrontal cortex (PFC). Here, we tested the hypothesis that adolescent alcohol exposure would produce lasting alterations in physiology within the retrosplenial cortex (RSC), another region critical for associative learning that is reciprocally connected to the hippocampus and PFC. In support of this hypothesis, we found that adolescent intermittent ethanol (AIE) vapor exposure resulted in lasting reductions in intrinsic excitability in RSC pyramidal cells of adult mice. Importantly, these changes were sex-specific, occurring in males but not females. This work suggests that the RSC may be a key, vulnerable locus to the detrimental effects of adolescent alcohol.

neuroscience↗

bioRxiv2025

Lateral hypothalamus CRFR1 regulation of chronic binge drinking: divergence along anterior-posterior axis

Binge alcohol drinking increases the risk of developing an alcohol use disorder (AUD) and comorbid psychopathology. The lateral hypothalamus (LH) is a brain structure that integrates cognitive and sensory information to tightly regulate motivated behavior, including binge drinking. Importantly, LH function is vulnerable to modulation by the pro-stress neuropeptide corticotropin-releasing factor (CRF), and acute antagonism of CRF receptor 1 (CRFR1) in the LH blunts binge drinking. However, the role of LH CRFR1 in chronic binge drinking is unknown. We used genetically targeted knockdown (KD) of CRFR1 in the LH of male and female mice followed by three weeks of binge drinking using the "Drinking in the Dark" (DID) model. CRFR1 KD in the posterior LH increased alcohol consumption, independent of sex, with no effect of KD in the anterior LH. Consistent with this, total alcohol consumption was negatively correlated with the location of CRFR1 KD in the LH along the anterior-posterior axis. CRFR1 KD did not alter water consumption or body weight, suggesting the effects of CRFR1 KD on alcohol consumption were not due to broad disruption of fluid intake or homeostatic function. In contrast to the observed effects on binge drinking, CRFR1 KD increased anxiety-like behavior and blunted sucrose preference, independent of KD location in the LH. Our findings provide foundational insight into LH function in the context of AUD and prompt further investigation into the divergent roles that distinct circuitry or cell populations along the anterior-posterior axis of the LH may play in binge drinking. HighlightsO_LICRFR1 knockdown in posterior LH increased alcohol drinking independent of sex C_LIO_LIAlcohol intake negatively correlated with AP location of CRFR1 knockdown in LH C_LIO_LICRFR1 knockdown was anxiogenic with more pronounced effects in females C_LIO_LISucrose preference was blunted by CRFR1 knockdown C_LI

neuroscience↗

bioRxiv2024

Dorsal Raphe to Basolateral Amygdala Corticotropin-Releasing Factor Circuit Regulates Cocaine-Memory Reconsolidation

Environmental stimuli elicit drug craving and relapse in cocaine users by triggering the retrieval of strong cocaine-related contextual memories. Retrieval can also destabilize drug memories, requiring reconsolidation, a protein synthesis-dependent storage process, to maintain memory strength. Corticotropin-releasing factor (CRF) signaling in the basolateral amygdala (BLA) is necessary for cocaine-memory reconsolidation. We have hypothesized that a critical source of CRF in the BLA is the dorsal raphe nucleus (DR) based on its neurochemistry, anatomical connectivity, and requisite involvement in cocaine-memory reconsolidation. To test this hypothesis, male and female Sprague-Dawley rats received adeno-associated viruses to express Gi-coupled designer receptors exclusively activated by designer drugs (DREADDs) selectively in CRF neurons of the DR and injection cannulae directed at the BLA. The rats were trained to self-administer cocaine in a distinct environmental context then received extinction training in a different context. They were then briefly re-exposed to the cocaine-predictive context to destabilize (reactivate) cocaine memories. Intra-BLA infusions of the DREADD agonist deschloroclozapine (DCZ; 0.1 mM, 0.5 L/hemisphere) after memory reactivation attenuated cocaine-memory strength, relative to vehicle infusion. This was indicated by a selective, DCZ-induced and memory reactivation-dependent decrease in drug-seeking behavior in the cocaine-predictive context in DREADD-expressing males and females at test compared to respective controls. Notably, BLA-projecting DR CRF neurons that exhibited increased c-Fos expression during memory reconsolidation co-expressed glutamatergic and serotonergic neuronal markers. Together, these findings suggest that the DRCRF [->] BLA circuit is engaged to maintain cocaine-memory strength after memory destabilization, and this phenomenon may be mediated by DR CRF, glutamate, and/or serotonin release in the BLA.

neuroscience↗

bioRxiv2021

Optogenetic inhibition of the dorsal hippocampus CA3 region during early-stage cocaine-memory reconsolidation disrupts subsequent context-induced cocaine seeking in rats

The dorsal hippocampus (DH) is key to the long-term maintenance of cocaine memories following retrieval-induced memory destabilization; even though, it is not the site of protein synthesis-dependent memory reconsolidation. Here, we took advantage of the temporal and spatial specificity of an optogenetic manipulation to examine the role of the cornu ammonis 3 subregion of the DH (dCA3) in early-stage cocaine-memory reconsolidation. Male Sprague-Dawley rats expressing eNpHR3.0 in the DH were trained to self-administer cocaine in a distinct context and underwent extinction training in a different context. Rats then received a 15-min memory-reactivation session, to destabilize cocaine memories and trigger reconsolidation, or remained in their home cages (no-reactivation controls). Optogenetic inhibition of the dCA3 for 1 h immediately, but not 1 h, after memory reactivation resulted in cocaine-memory impairment as indicated by reduction in drug-seeking behavior selectively in the cocaine-paired context 3 d later, at test, relative to responding in no-inhibition, no-reactivation, and no-eNpHR3.0 controls. Cocaine-memory impairment was associated with reduced c-Fos expression, an index of neuronal activation, in the dCA3 stratum lucidum (SL) and stratum pyramidale (SP) at test. Based on these observations and extant literature, we postulate that recurrent circuits in the SP are activated during early-stage memory reconsolidation to maintain labile cocaine memories prior to protein synthesis-dependent restabilization in another brain region, such as the basolateral amygdala. Furthermore, SL and SP interneurons may enhance memory reconsolidation by limiting synaptic noise in the SP and also contribute to recall as elements of the updated cocaine engram or retrieval links.

neuroscience↗