M.K.P. Joyce, S. Yang, K. Morin, A. Duque, J. Arellano, D. Datta, M. Wang, A.F.T. Arnsten
{"title":"灵长类背外侧前额叶皮层 GABA 能中间神经元上的β1-肾上腺素受体表达:在压力诱导的认知功能障碍中的潜在作用","authors":"M.K.P. Joyce, S. Yang, K. Morin, A. Duque, J. Arellano, D. Datta, M. Wang, A.F.T. Arnsten","doi":"10.1016/j.ynstr.2024.100628","DOIUrl":null,"url":null,"abstract":"<div><p>Uncontrollable stress exposure impairs working memory and reduces the firing of dorsolateral prefrontal cortex (dlPFC) “Delay cells”, involving high levels of norepinephrine and dopamine release. Previous work has focused on catecholamine actions on dlPFC pyramidal cells, but inhibitory interneurons may contribute as well. The current study combined immunohistochemistry and multi-scale microscopy with iontophoretic physiology and behavioral analyses to examine the effects of beta1-noradrenergic receptors (β1-ARs) on inhibitory neurons in layer III dlPFC. We found β1-AR robustly expressed on different classes of inhibitory neurons labeled by the calcium-binding proteins calbindin (CB), calretinin (CR), and parvalbumin (PV). Immunoelectron microscopy confirmed β1-AR expression on the plasma membrane of PV-expressing dendrites. PV interneurons can be identified as fast-spiking (FS) in physiological recordings, and thus were studied in macaques performing a working memory task. Iontophoresis of a β1-AR agonist had a mixed effect, increasing the firing of a subset and decreasing the firing of others, likely reflecting loss of firing of the entire microcircuit. This loss of overall firing likely contributes to impaired working memory during stress, as pretreatment with the selective β1-AR antagonist, nebivolol, prevented stress-induced working memory deficits. Thus, selective β1-AR antagonists may be helpful in treating stress-related disorders.</p></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"30 ","pages":"Article 100628"},"PeriodicalIF":4.3000,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352289524000249/pdfft?md5=46d28d2d6f2a21c3801598b596f48a07&pid=1-s2.0-S2352289524000249-main.pdf","citationCount":"0","resultStr":"{\"title\":\"β1-adrenoceptor expression on GABAergic interneurons in primate dorsolateral prefrontal cortex: potential role in stress-induced cognitive dysfunction\",\"authors\":\"M.K.P. Joyce, S. Yang, K. Morin, A. Duque, J. Arellano, D. Datta, M. Wang, A.F.T. Arnsten\",\"doi\":\"10.1016/j.ynstr.2024.100628\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Uncontrollable stress exposure impairs working memory and reduces the firing of dorsolateral prefrontal cortex (dlPFC) “Delay cells”, involving high levels of norepinephrine and dopamine release. Previous work has focused on catecholamine actions on dlPFC pyramidal cells, but inhibitory interneurons may contribute as well. The current study combined immunohistochemistry and multi-scale microscopy with iontophoretic physiology and behavioral analyses to examine the effects of beta1-noradrenergic receptors (β1-ARs) on inhibitory neurons in layer III dlPFC. We found β1-AR robustly expressed on different classes of inhibitory neurons labeled by the calcium-binding proteins calbindin (CB), calretinin (CR), and parvalbumin (PV). Immunoelectron microscopy confirmed β1-AR expression on the plasma membrane of PV-expressing dendrites. PV interneurons can be identified as fast-spiking (FS) in physiological recordings, and thus were studied in macaques performing a working memory task. Iontophoresis of a β1-AR agonist had a mixed effect, increasing the firing of a subset and decreasing the firing of others, likely reflecting loss of firing of the entire microcircuit. This loss of overall firing likely contributes to impaired working memory during stress, as pretreatment with the selective β1-AR antagonist, nebivolol, prevented stress-induced working memory deficits. 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β1-adrenoceptor expression on GABAergic interneurons in primate dorsolateral prefrontal cortex: potential role in stress-induced cognitive dysfunction
Uncontrollable stress exposure impairs working memory and reduces the firing of dorsolateral prefrontal cortex (dlPFC) “Delay cells”, involving high levels of norepinephrine and dopamine release. Previous work has focused on catecholamine actions on dlPFC pyramidal cells, but inhibitory interneurons may contribute as well. The current study combined immunohistochemistry and multi-scale microscopy with iontophoretic physiology and behavioral analyses to examine the effects of beta1-noradrenergic receptors (β1-ARs) on inhibitory neurons in layer III dlPFC. We found β1-AR robustly expressed on different classes of inhibitory neurons labeled by the calcium-binding proteins calbindin (CB), calretinin (CR), and parvalbumin (PV). Immunoelectron microscopy confirmed β1-AR expression on the plasma membrane of PV-expressing dendrites. PV interneurons can be identified as fast-spiking (FS) in physiological recordings, and thus were studied in macaques performing a working memory task. Iontophoresis of a β1-AR agonist had a mixed effect, increasing the firing of a subset and decreasing the firing of others, likely reflecting loss of firing of the entire microcircuit. This loss of overall firing likely contributes to impaired working memory during stress, as pretreatment with the selective β1-AR antagonist, nebivolol, prevented stress-induced working memory deficits. Thus, selective β1-AR antagonists may be helpful in treating stress-related disorders.
期刊介绍:
Neurobiology of Stress is a multidisciplinary journal for the publication of original research and review articles on basic, translational and clinical research into stress and related disorders. It will focus on the impact of stress on the brain from cellular to behavioral functions and stress-related neuropsychiatric disorders (such as depression, trauma and anxiety). The translation of basic research findings into real-world applications will be a key aim of the journal.
Basic, translational and clinical research on the following topics as they relate to stress will be covered:
Molecular substrates and cell signaling,
Genetics and epigenetics,
Stress circuitry,
Structural and physiological plasticity,
Developmental Aspects,
Laboratory models of stress,
Neuroinflammation and pathology,
Memory and Cognition,
Motivational Processes,
Fear and Anxiety,
Stress-related neuropsychiatric disorders (including depression, PTSD, substance abuse),
Neuropsychopharmacology.