Emotional stress in mammals triggers a diverse but highly stereotyped pattern of physiological changes, and these are thought to contribute to a wide variety of human disorders and disease states. While the central mechanisms and pathways mediating these changes are largely unknown, the hypothalamus has long been conceded to embody the neural """"""""command center"""""""" for the stress response. For nearly two decades the primary role for the hypothalamic integration of the autonomic and neuroendocrine response to stress has been attributed - virtually unchallenged - to the paraventricular nucleus of the hypothalamus (PVN). However, previous findings from the applicants indicate that neurons responsible for generating the autonomic - particularly the cardiovascular - changes associated with stress are found in the region of the dorsomedial hypothalamic nucleus (DMH) and not the PVN. The studies planned will extend these published findings and expand upon more recent preliminary data to 1) test the hypothesis that neurons in the region of the DMH - and not the PVN - are responsible for the integrated autonomic and neuroendocrine response to stress, and 2) identify the local neurons and the central neural pathways that may mediate these effects.
The specific aims are to 1) characterize the effect of chemical stimulation of the DMH on plasma ACTH in conscious rats, and examine the effect of inhibition and lesion of neurons in the DMH and the PVN on the increase in plasma ACTH, heart rate and blood pressure seen in air stress, 2) compare the effect of air stress and of chemical stimulation of the DMH on the pattern of stress-induced Fos expression in the brain in conscious rats, and assess the effect of inhibition and lesion of neurons in the DMH on this pattern, with particular attention to the nearby PVN, and to vagal and sympathetic preganglionic neurons in the brainstem and spinal cord, and 3) identify the specific neurons in the region of the DMH and their efferent projections that are likely to be responsible for these changes by a combination of high-resolution functional mapping of the region, localization of stress-induced Fos expression, and anterograde and retrograde tracer studies. The experiments proposed will enhance our understanding of the DMH and its place in hypothalamic circuitry and function, and in so doing should provide the basis for revolutionizing current thinking regarding the location of hypothalamic neurons integrating the multi-system physiologic response to stress.
| Jiang, Peng; Chen, Chen; Liu, Xiao-Bo et al. (2016) Human iPSC-Derived Immature Astroglia Promote Oligodendrogenesis by Increasing TIMP-1 Secretion. Cell Rep 15:1303-15 |
| Zaretsky, Dmitry V; Zaretskaia, Maria V; DiMicco, Joseph A (2016) Characterization of the relationship between spontaneous locomotor activity and cardiovascular parameters in conscious freely moving rats. Physiol Behav 154:60-7 |
| Zaretsky, Dmitry V; Zaretskaia, Maria V; DiMicco, Joseph A et al. (2015) Yohimbine is a 5-HT1A agonist in rats in doses exceeding 1 mg/kg. Neurosci Lett 606:215-9 |
| Müller-Ribeiro, Flávia Camargos de Figueirêdo; Zaretsky, Dmitry V; Zaretskaia, Maria V et al. (2012) Contribution of infralimbic cortex in the cardiovascular response to acute stress. Am J Physiol Regul Integr Comp Physiol 303:R639-50 |
| Fontes, M A P; Xavier, C H; de Menezes, R C A et al. (2011) The dorsomedial hypothalamus and the central pathways involved in the cardiovascular response to emotional stress. Neuroscience 184:64-74 |
| Rusyniak, Daniel E; Zaretsky, Dmitry V; Zaretskaia, Maria V et al. (2011) The role of orexin-1 receptors in physiologic responses evoked by microinjection of PgE2 or muscimol into the medial preoptic area. Neurosci Lett 498:162-6 |
| Zaretsky, Dmitry V; Zaretskaia, Maria V; Rusyniak, Daniel E et al. (2011) Stress-free microinjections in conscious rats. J Neurosci Methods 199:199-207 |
| Hunt, Joseph L; Zaretsky, Dmitry V; Sarkar, Sumit et al. (2010) Dorsomedial hypothalamus mediates autonomic, neuroendocrine, and locomotor responses evoked from the medial preoptic area. Am J Physiol Regul Integr Comp Physiol 298:R130-40 |
| Zaretsky, Dmitry V; Molosh, Andrei I; Zaretskaia, Maria V et al. (2010) Increase in plasma ACTH induced by urethane is not a consequence of hyperosmolality. Neurosci Lett 479:10-2 |
| de Menezes, Rodrigo C A; Zaretsky, Dmitry V; Fontes, Marco A P et al. (2009) Cardiovascular and thermal responses evoked from the periaqueductal grey require neuronal activity in the hypothalamus. J Physiol 587:1201-15 |
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