How are emotions generated in the brain? To address this question, we study the molecular mechanisms that control the physiological expression of anxiety and fear. An important modulator of anxiety is the neuropeptide oxytocin. Oxytocin has anxiolytic effects when released in the amygdala or the hypothalamic paraventricular nucleus (PVN) in rodents, and increases trust and promotes social engagement in humans.
Oxytocin exerts its effects through binding to its specific receptor, followed by the activation of a plethora of intracellular signalling cascades. These cascades subsequently change neuronal excitability, protein synthesis, and gene expression, leading to immediate and long-term neurophysiological adaptations. We not only aim to identify which intracellular factors contribute to the anxiolytic effect of oxytocin, but also try to better understand how they interact with each other. This touches on the fundamental question of how simultaneous activation and inhibition of many intracellular factors leads to an appropriate neuronal response to an external stimulus.
Our current research focuses on the role of MAPK and Ca2+ signalling pathways, and those controlling protein synthesis as well as mRNA and microRNA expression. In addition to biochemical and molecular techniques, we employ behavioural tests to assess the role of identified factors in oxytocin-induced anxiolysis. Our studies are supported by the Deutsche Forschungsgemeinschaft (DFG NE 465/19-1).
Junior Group Leader
Erwin H. van den Burg
Intracellular signalling cascades and gene expression
Gene expression, protein synthesis and microRNA analysis
- Dr. G. Aguilera, NIH, Bethesda, USA
- Dr. R. Deutzmann, University of Regensburg, Germany
- Dr. G. Meister, University of Regensburg, Germany
- Dr. R. Ring, Autism Speaks, USA
- Dr. O. Strauss, University Medical Centre, Regensburg, Germany
- Dr. C. Waller, University of Ulm, Germany
Neumann ID, Van den Burg EH. Oxytocin and vasopressin release and their receptor-mediated intracellular pathways that determine their behavioral effects. In: Oxytocin, Vasopressin and Related Peptides in the Regulation of Behavior. Choleris E, Pfaff DW, Kavaliers M (Eds), Cambridge University Press.
Jurek B, Slattery DS, Maloumby R, Hillerer K, Koszinowski S, Neumann ID, Van den Burg EH. Differential contribution of hypothalamic MAPK activity to anxiety-like behaviour in virgin and lactating rats. PLoS ONE 7: e37060.
Viviani D, Charlet A, Van den Burg E, Robinet C, Hurni N, Abatis M, Magara F, Stoop R. Oxytocin selectively gates fear responses through distinct outputs from the central amygdala. Science 333: 104-107.
Van den Burg EH, Neumann ID. Bridging the gap between GPCR activation and behaviour: Oxytocin and prolactin signalling in the hypothalamus. J. Mol. Neurosci. 43: 200-208.
Engelmann J, Van den Burg E, Bacelo J, De Ruijters M, Grant K, Sugawara Y. Analysis of backpropagation in interneurons of the mormyrid electrosensory lateral line lobe. J. Physiol. (Paris) 102: 233-245.
Van den Burg EH, Engelmann J, Bacelo J, Gómez L, Grant K. Etomidate reduces initiation of backpropagating dendritic action potentials: implications for sensory processing and synaptic plasticity during anesthesia. J. Neurophysiol. 97: 2373-238.
Flik G, Klaren PHM, Van den Burg EH, Metz JR, Huising MO. CRH and stress in fish. Gen. Comp. Endocrinol. 146: 36-44.
Van den Burg EH, Verhoye M, Peeters RR, Meek J, Flik G, Van der Linden A. Activation of a sensorimotor pathway in response to a water temperature drop in a teleost fish. J. Exp. Biol. 209: 2015-2024.
Engelmann J, Bacelo J, Van den Burg EH, Grant K. Sensory and motor effects of etomidate anaesthesia. J. Neurophysiol. 95: 1231-1243.
Flik G, Van Kemenade BML, Van den Burg EH, Klaren PM, Stolte EJH, Geven E, Metz JR, Huising MO. CRF and stress in fish. J. Exp. Zool. A Comp. Exp. Biol. 305A: 126.
Metz JR, Geven EDW, Van den Burg EH, Flik G. ACTH, α-MSH and control of cortisol release: Cloning, sequencing and functional expression of the melanocortin-2 and melanocortin-5 receptors in Cyprinus carpio. Am. J. Physiol. Regul. Integr. Comp. Physiol. 289: R814-R826.
Van den Burg EH, Peeters RR, Verhoye M, Meek J, Flik G, Van der Linden A. Brain responses to ambient temperature fluctuations in fish: reduction of blood volume and initiation of a whole-body stress response. J. Neurophysiol. 93: 2849-2855.
Van den Burg EH, Metz JR, Spanings FAT, Wendelaar Bonga SE, Flik G. Plasma α-MSH and acetylated β-endorphin levels following stress vary according to CRH sensitivity of the pituitary melanotropes in common carp, Cyprinus carpio. Gen. Comp. Endocrinol. 140: 210-221.
Metz JR, Van den Burg EH, Wendelaar Bonga SE, Flik G. Regulation of branchial Na+/K+-ATPase in common carp Cyprinus carpio L. acclimated to different temperatures. J. Exp. Biol. 206: 2273-2280.
Van den Burg EH, Metz JR, Ross HA, Darras VM, Wendelaar Bonga SE, Flik G. Temperature-induced changes of TRH-sensitivity of carp melanotropes. Neuroendocrinology 77: 15-23.
Van den Burg EH, Metz JR, Arends RJ, Vandenberghe I, Devreese B, Van Beeumen J, Wendelaar Bonga SE, Flik G. Identification of β-endorphin isoforms in the pituitary gland and blood plasma of the common carp (Cyprinus carpio L.). J. Endocrinol. 169: 271-280.
Mensink A, Brouwer A, Van den Burg EH, Geurts S, Jongen WMF, Lakemond CMM, Meijerman I Van der Wijk T. Modulation of intercellular communication between smooth muscle cells by growth factors and cytokines. Eur. J. Pharmacol. 310: 73-81.