title: Endogenous brain-derived neurotrophic factor in the nucleus tractus solitarius tonically regulates synaptic and autonomic function.
abstract: Brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, are highly expressed in the nucleus tractus solitarius (nTS), the principal target of cardiovascular primary afferent input to the brainstem. However, little is known about the role of BDNF signaling in nTS in cardiovascular homeostasis. We examined whether BDNF in nTS modulates cardiovascular function in vivo and regulates synaptic and/or neuronal activity in isolated brainstem slices. Microinjection of BDNF into the rat medial nTS (mnTS), a region critical for baroreflex control of sympathetic outflow, produced dose-dependent increases in mean arterial pressure (MAP), heart rate (HR), and lumbar sympathetic nerve activity (LSNA) that were blocked by the tyrosine kinase inhibitor K252a. In contrast, immunoneutralization of endogenous BDNF (anti-BDNF), or microinjection of K252a alone, decreased MAP, HR, and LSNA. The effects of anti-BDNF were abolished by blockade of ionotropic glutamate receptors, indicating a role for glutamate signaling in the response to BDNF. In vitro, BDNF reduced the amplitude of miniature EPSCs as well as solitary tract (TS) evoked EPSC amplitude and action potential discharge (APD) in second-order nTS neurons. BDNF effects on EPSCs were independent of GABAergic signaling and abolished by AMPA receptor blockade. In contrast, K252a increased spontaneous EPSC frequency and TS evoked EPSC amplitude. BDNF also attenuated APD evoked by injection of depolarizing current into second-order neurons, indicating reduced intrinsic neuronal excitability. Our data demonstrate that BDNF signaling in mnTS plays a tonic role in regulating cardiovascular function, likely via modulation of primary afferent glutamatergic excitatory transmission and neural activity.
authors.affiliation: Dalton Cardiovascular Research Center, Department of Biomedical Sciences, University of Missouri, Columbia, Missouri 65211, USA.
authors.forename: Catharine G
authors.initials: CG
authors.lastname: Clark
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Hasser
authors.forename: Diana L
authors.initials: DL
authors.lastname: Kunze
authors.forename: David M
authors.initials: DM
authors.lastname: Katz
authors.forename: David D
authors.initials: DD
authors.lastname: Kline
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D017776:Autonomic Pathways / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D002320:Cardiovascular Physiological Phenomena; D008297:Male; D009474:Neurons / Q000502:physiology*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor