RESUMEN
Circadian clocks keep time to coordinate diverse behaviors and physiological functions. While molecular circadian rhythms are evident during early development, most behavioral rhythms, such as sleep-wake, do not emerge until far later. Here, we examine the development of circadian clocks, outputs, and behaviors across phylogeny, with a particular focus on Drosophila. We explore potential mechanisms for how central clocks and circadian output loci establish communication, and discuss why from an evolutionary perspective sleep-wake and other behavioral rhythms emerge long after central clocks begin keeping time.
Asunto(s)
Relojes Circadianos , Proteínas de Drosophila , Animales , Relojes Circadianos/genética , Ritmo Circadiano/genética , Sueño/genética , Drosophila/genéticaRESUMEN
Opioid addiction is a chronic, relapsing disorder associated with persistent changes in brain plasticity. Reconfiguration of neuronal connectivity may explain heightened abuse liability in individuals with a history of chronic drug exposure. To characterize network-level changes in neuronal activity induced by chronic opiate exposure, we compared FOS expression in mice that are morphine-naïve, morphine-dependent, or have undergone 4 wk of withdrawal from chronic morphine exposure, relative to saline-exposed controls. Pairwise interregional correlations in FOS expression data were used to construct network models that reveal a persistent reduction in connectivity strength following opiate dependence. Further, we demonstrate that basal gene expression patterns are predictive of changes in FOS correlation networks in the morphine-dependent state. Finally, we determine that regions of the hippocampus, striatum, and midbrain are most influential in driving transitions between opiate-naïve and opiate-dependent brain states using a control theoretic approach. This study provides a framework for predicting the influence of specific therapeutic interventions on the state of the opiate-dependent brain.
Asunto(s)
Encéfalo/fisiopatología , Dependencia de Morfina/fisiopatología , Red Nerviosa/fisiopatología , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversos , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Conectoma , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Masculino , Ratones , Ratones Endogámicos C57BL , Modelos Neurológicos , Morfina/administración & dosificación , Morfina/efectos adversos , Dependencia de Morfina/metabolismo , Red Nerviosa/efectos de los fármacos , Red Nerviosa/metabolismo , Plasticidad Neuronal/genética , Proteínas Proto-Oncogénicas c-fos/genética , Proteínas Proto-Oncogénicas c-fos/metabolismo , Síndrome de Abstinencia a Sustancias/genética , Síndrome de Abstinencia a Sustancias/metabolismo , Síndrome de Abstinencia a Sustancias/fisiopatologíaRESUMEN
Maternal behavior (MB) is a complex response to infant cues, orchestrated by postpartum neurophysiology. Although mesolimbic dopamine contributes toward MB, little is known about real-time dopamine fluctuations during the postpartum period. Thus, we used fast-scan cyclic voltammetry to measure individual dopamine transients in the nucleus accumbens of early postpartum rats and compared them with dopamine transients in virgins and in postpartum females exposed to cocaine during pregnancy, which is known to disrupt MB. We hypothesized that dopamine transients are normally enhanced postpartum and support MB. In anesthetized rats, electrically evoked dopamine release was larger and clearance was faster in postpartum females than in virgins and gestational cocaine exposure blocked the change in clearance. In awake rats, control mothers showed more dopamine transients than cocaine-exposed mothers during MB. Salient pup-produced stimuli may contribute toward differences in maternal phasic dopamine by evoking dopamine transients; supporting the feasibility of this hypothesis, urine composition (glucose, ketones, and leukocytes) differed between unexposed and cocaine-exposed infants. These data, resulting from the novel application of fast-scan cyclic voltammetry to models of MB, support the hypothesis that phasic dopamine signaling is enhanced postpartum. Future studies with additional controls can delineate which aspects of gestational cocaine reduce dopamine clearance and transient frequency.