A Transgenic Rat for Investigating the Anatomy and Function of Corticotrophin Releasing Factor Circuits
| Autor: | F. Woodward Hopf, Kenner C. Rice, Matthew B. Pomrenze, E. Zayra Millan, Giordano de Guglielmo, Ronald Keiflin, Angelo Blasio, Rajani Maiya, Viktor Kharazia, Patricia H. Janak, Robert O. Messing, Olivier George, Jahan Dadgar, Elena Crawford |
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| Rok vydání: | 2015 |
| Předmět: |
endocrine system
Lateral hypothalamus designer receptors exclusively activated by designer drugs Neuropeptide Substantia nigra Cre recombinase Biology Optogenetics Basic Behavioral and Social Science lcsh:RC321-571 Endocrinology Behavioral and Social Science medicine Methods 2.1 Biological and endogenous factors Psychology R121919 channelrhodopsin-2 lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry transgenic rat models Central nucleus of the amygdala General Neuroscience Fos Neurosciences Anatomy CRF Ventral tegmental area medicine.anatomical_structure nervous system central amygdala Locus coeruleus Cognitive Sciences Brainstem Neuroscience hormones hormone substitutes and hormone antagonists |
| Zdroj: | Frontiers in neuroscience, vol 9, iss DEC Frontiers in Neuroscience, Vol 9 (2015) Frontiers in Neuroscience |
| Popis: | Corticotrophin-releasing factor (CRF) is a 41 amino acid neuropeptide that coordinates adaptive responses to stress. CRF projections from neurons in the central nucleus of the amygdala (CeA) to the brainstem are of particular interest for their role in motivated behavior. To directly examine the anatomy and function of CRF neurons, we generated a BAC transgenic Crh-Cre rat in which bacterial Cre recombinase is expressed from the Crh promoter. Using Cre-dependent reporters, we found that Cre expressing neurons in these rats are immunoreactive for CRF and are clustered in the lateral CeA (CeL) and the oval nucleus of the BNST. We detected major projections from CeA CRF neurons to parabrachial nuclei and the locus coeruleus, dorsal and ventral BNST, and more minor projections to lateral portions of the substantia nigra, ventral tegmental area, and lateral hypothalamus. Optogenetic stimulation of CeA CRF neurons evoked GABA-ergic responses in 11% of non-CRF neurons in the medial CeA (CeM) and 44% of non-CRF neurons in the CeL. Chemogenetic stimulation of CeA CRF neurons induced Fos in a similar proportion of non-CRF CeM neurons but a smaller proportion of non-CRF CeL neurons. The CRF1 receptor antagonist R121919 reduced this Fos induction by two-thirds in these regions. These results indicate that CeL CRF neurons provide both local inhibitory GABA and excitatory CRF signals to other CeA neurons, and demonstrate the value of the Crh-Cre rat as a tool for studying circuit function and physiology of CRF neurons. |
| Databáze: | OpenAIRE |
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