Our goal is to identify, at systems-, cellular- and molecular levels, pathways and mechanisms that regulate and coordinate autonomic, neuroendocrine and immune responses to internal and external challenges at the hypothalamic level.
Neurosecretory cells of the hypothalamus receive afferent neural inputs from all sensory modalities of the central nervous system and express receptors for circulating signaling molecules such as steroid hormones, metabolic- and immune signals. Hypothalamic neurons are in the position to integrate this information and to generate a relevant output command to neuronal and humoral effectors in response to various external and internal stimuli. These functions are all represented in the hypothalamic paraventricular nucleus, where neurosecretory neurons of the medial dorsal parvocellular subdivision supply corticotropin-releasing hormone and various other neuropeptides to the pituitary portal circulation to initiate the neuroendocrine stress cascade, magnocellular neurosecretory cells that respond to osmotic challenges and autonomic projection neurons that give rise to long descending pathways to the brain stem and spinal cord.
Using molecular biological techniques, regulation of expression of the corticotropin-releasing hormone and arginine vasopressin genes are studied in vivo. Cells and circuitries, which are recruited in response to various physical, psychological and immune challenges are mapped using functional anatomical methods. Transcription factors and their interactions regulating stress-related gene expression in the hypothalamus are examined. We study mechanisms that constrain activity of the hypothalamo-pituitary-adrenocortical axis, with special attention on the neurotransmitter GABA and the negative feedback effect of the glucocorticoid hormones. We aim to elucidate the role of peripheral metabolic signals in coordination of bodily responses to stress.
We study the relationship between hypothalamo-pituitary-adrenal axis and gut microbiome. Our aim is to develop psychobiotics with which to manipulate stress-related brain circuits in health and disease.
The results may contribute to the understanding of various stress-related disorders such as hypertension, auto-immune diseases, affective and eating disorders, depression, post-traumatic stress disorder, panic and anxiety.