Chronic BDNF simultaneously inhibits and unmasks superficial dorsal horn neuronal activity

Sci Rep. 2021 Jan 26;11(1):2249. doi: 10.1038/s41598-021-81269-6.

Abstract

Brain-derived neurotrophic factor (BDNF) is critically involved in the pathophysiology of chronic pain. However, the mechanisms of BDNF action on specific neuronal populations in the spinal superficial dorsal horn (SDH) requires further study. We used chronic BDNF treatment (200 ng/ml, 5-6 days) of defined-medium, serum-free spinal organotypic cultures to study intracellular calcium ([Ca2+]i) fluctuations. A detailed quantitative analysis of these fluctuations using the Frequency-independent biological signal identification (FIBSI) program revealed that BDNF simultaneously depressed activity in some SDH neurons while it unmasked a particular subpopulation of 'silent' neurons causing them to become spontaneously active. Blockade of gap junctions disinhibited a subpopulation of SDH neurons and reduced BDNF-induced synchrony in BDNF-treated cultures. BDNF reduced neuronal excitability assessed by measuring spontaneous excitatory postsynaptic currents. This was similar to the depressive effect of BDNF on the [Ca2+]i fluctuations. This study reveals novel regulatory mechanisms of SDH neuronal excitability in response to BDNF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Octanol / pharmacology
  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Brain-Derived Neurotrophic Factor / pharmacology*
  • Calcium / metabolism
  • Cluster Analysis
  • Excitatory Postsynaptic Potentials / drug effects
  • Gap Junctions / drug effects
  • Gap Junctions / metabolism
  • Models, Neurological
  • Posterior Horn Cells / drug effects
  • Posterior Horn Cells / physiology*
  • Rats

Substances

  • Brain-Derived Neurotrophic Factor
  • 1-Octanol
  • Calcium