PhD Scientific Days 2019

Budapest, April 25–26, 2019

Hypothalamic CNTF volume transmission shapes cortical noradrenergic excitability upon acute stress

Zahola, Péter

Péter Zahola1,2, János Hanics1,2, Zsófia Hevesi1,2, Solomiia Korchynska3, Marco Benevento3, Christian Pifl3, Gergely Zachar2, Andras G Miklosi3, Zoltán Máté4, Ferenc Erdélyi4, Gábor Szabó4, Miklós Palkovits5, Tomas GM Hökfelt6, Roman A Romanov3,Tamas L Horvath7,8, Tibor Harkany3, Alán Alpár1,2

1-2 SE NAP Research Group of Experimental Neuroanatomy and Developmental Biology, Hungarian Brain Research Program, Department of Anatomy, Histology, and Embryology, Semmelweis University, Budapest, Hungary;
3 Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Austria;
4 Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary;
5 Human Brain Tissue Bank and Laboratory, Semmelweis University;
6 Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden;
7 Departments of Comparative Medicine and Neuroscience, Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT, USA;
8 Department of Anatomy and Histology, University of Veterinary Medicine, Budapest, Hungary

Language of the presentation

Hungarian

Text of the abstract

Stress-induced cortical alertness is maintained by a heightened excitability of noradrenergic neurons innervating, notably, the prefrontal cortex. However, neither the signaling axis linking hypothalamic activation to delayed and lasting noradrenergic excitability nor the molecular cascade gating noradrenaline synthesis is defined. Here, we show that hypothalamic corticotropin-releasing hormone-releasing neurons innervate ependymal cells of the 3rd ventricle to induce ciliary neurotrophic factor (CNTF) release for transport through the brain's aqueductal system. CNTF binding to its cognate receptors on norepinephrinergic neurons in the locus coeruleus then initiates sequential phosphorylation of extracellular signal-regulated kinase 1 and tyrosine hydroxylase with the Ca2+- sensor secretagogin ensuring activity dependence in both rodent and human brains. Both CNTF and secretagogin ablation occlude stress-induced cortical norepinephrine synthesis, ensuing neuronal excitation and behavioral stereotypes. Cumulatively, we identify a multimodal pathway that is rate limited by CNTF volume transmission and poised to directly convert hypothalamic activation into long-lasting cortical excitability following acute stress.

Data of the presenter

Doctoral School: János Szentágothai Doctoral School of Neurosciences
Program: Neuromorphology and Cell Biology
Supervisor: Alán Alpár
E-mail address: zahola.peter@gmail.com