1. Institut für Physiologie, Ludwig-Maximilians-Universität München, 80336 München, Germany

Correspondence to: Christine R. Rose¹Arthur Konnerth¹ Email: rose@lrz.uni-muenchen.de
Email: konnerth@lrz.uni-muenchen.de

Abstract

The neurotrophin receptor TrkB is essential for normal function of the mammalian brain^{1, 2, 3}. It is expressed in three splice variants. Full-length receptors (TrkB^FL) possess an intracellular tyrosine kinase domain and are considered as those TrkB receptors that mediate the crucial effects of brain-derived neurotrophic factor (BDNF) or neurotrophin 4/5 (NT-4/5). By contrast, truncated receptors (TrkB-T1 and TrkB-T2) lack tyrosine kinase activity and have not been reported to elicit rapid intracellular signalling⁴. Here we show that astrocytes predominately express TrkB-T1 and respond to brief application of BDNF by releasing calcium from intracellular stores. The calcium transients are insensitive to the tyrosine kinase blocker K-252a and persist in mutant mice lacking TrkB^FL. By contrast, neurons produce rapid BDNF-evoked signals through TrkB^FL and the Na_v1.9 channel^{5, 6}. Expression of antisense TrkB messenger RNA strongly reduces BDNF-evoked calcium signals in glia. Thus, our results show that, unexpectedly, TrkB-T1 has a direct signalling role in mediating inositol-1,4,5-trisphosphate-dependent calcium release; in addition, they identify a previously unknown mechanism of neurotrophin action in the brain.