Dataset Information

Topographical distribution of corticotropin-releasing factor type 2 receptor-like immunoreactivity in the rat dorsal raphe nucleus: co-localization with tryptophan hydroxylase.

ABSTRACT: Corticotropin-releasing factor (CRF) and CRF-related neuropeptides are involved in the regulation of stress-related physiology and behavior. Members of the CRF family of neuropeptides bind to two known receptors, the CRF type 1 (CRF?) receptor, and the CRF type 2 (CRF?) receptor. Although the distribution of CRF? receptor mRNA expression has been extensively studied, the distribution of CRF? receptor protein has not been characterized. An area of the brain known to contain high levels of CRF? receptor mRNA expression and CRF? receptor binding is the dorsal raphe nucleus (DR). In the present study we investigated in detail the distribution of CRF? receptor immunoreactivity throughout the rostrocaudal extent of the DR. CRF? receptor-immunoreactive perikarya were observed throughout the DR, with the highest number and density in the mid-rostrocaudal DR. Dual immunofluorescence revealed that CRF? receptor immunoreactivity was frequently co-localized with tryptophan hydroxylase, a marker of serotonergic neurons. This study provides evidence that CRF? receptor protein is expressed in the DR, and that CRF? receptors are expressed in topographically organized subpopulations of cells in the DR, including serotonergic neurons. Furthermore, these data are consistent with the hypothesis that CRF? receptors play an important role in the regulation of stress-related physiology and behavior through actions on serotonergic and non-serotonergic neurons within the DR.

SUBMITTER: Lukkes JL

PROVIDER: S-EPMC3092641 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Topographical distribution of corticotropin-releasing factor type 2 receptor-like immunoreactivity in the rat dorsal raphe nucleus: co-localization with tryptophan hydroxylase.

Lukkes J L JL Staub D R DR Dietrich A A Truitt W W Neufeld-Cohen A A Chen A A Johnson P L PL Shekhar A A Lowry C A CA

Neuroscience 20110329

Corticotropin-releasing factor (CRF) and CRF-related neuropeptides are involved in the regulation of stress-related physiology and behavior. Members of the CRF family of neuropeptides bind to two known receptors, the CRF type 1 (CRF₁) receptor, and the CRF type 2 (CRF₂) receptor. Although the distribution of CRF₂ receptor mRNA expression has been extensively studied, the distribution of CRF₂ receptor protein has not been characterized. An area of the brain known to contain high levels of CRF₂ re ...[more]

PMID: 21453754

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Project description:Environmental stimuli elicit drug craving and relapse in cocaine users by triggering the retrieval of strong cocainerelated 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 cocainememory 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 reexposed to the cocaine-predictive context to destabilize (reactivate) cocaine memories. Intra-BLA infusions of the DREADD agonist deschloroclozapine (DCZ; 0.1 mM, 0.5 μL/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.

Project description:Previous neuroimaging studies have suggested that the experience of flow aligns with a relative increase in activation of the dorsal raphe nucleus (DRN), and relative activation decreases of the medial prefrontal cortex (MPFC) and of the amygdala (AMY). In the present study, Dynamic Causal Modeling (DCM) was used to explore effective connectivity between those brain regions. To test our hypothesis that the DRN causally down-regulates activity of the MPFC and/or of the AMY, 23 healthy male students solved mental arithmetic tasks of varying difficulty during functional magnetic resonance imaging. A "flow" condition, with task demands automatically balanced with participants' skill level, was compared with conditions of "boredom" and "overload". DCM models were constructed modeling full reciprocal endogenous connections between the DRN, the MPFC, the AMY, and the calcarine. The calcarine was included to allow sensory input to enter the system. Experimental conditions were modeled as exerting modulatory effects on various possible connections between the DRN, the MPFC, and the AMY, but not on self-inhibitory connections, yielding a total of 64 alternative DCM models. Model space was partitioned into eight families based on commonalities in the arrangement of the modulatory effects. Random effects Bayesian Model Selection (BMS) was applied to identify a possible winning family (and model). Although BMS revealed a clear winning family, an outstanding winning model could not be identified. Therefore, Bayesian Model Averaging was performed over models within the winning family to obtain representative DCM parameters for subsequent analyses to test our hypothesis. In line with our expectations, Bayesian averaged parameters revealed stronger down-regulatory influence of the DRN on the MPFC when participants experienced flow relative to control conditions. In addition, these condition-dependent modulatory effects significantly predicted participants' experienced degree of flow. The AMY was down-regulated irrespective of condition. The present results suggest a causal role for the DRN in modulating the MPFC, contributing to the experience of flow.

Dataset Information

Topographical distribution of corticotropin-releasing factor type 2 receptor-like immunoreactivity in the rat dorsal raphe nucleus: co-localization with tryptophan hydroxylase.

Publications

Topographical distribution of corticotropin-releasing factor type 2 receptor-like immunoreactivity in the rat dorsal raphe nucleus: co-localization with tryptophan hydroxylase.

Similar Datasets

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