BDNF enhances dendritic Ca2+ signals evoked by coincident EPSPs and back-propagating action potentials in CA1 pyramidal neurons.
BDNF, a member of the neurotrophin family, is emerging as a key modulator of synaptic structure and function in the CNS. Due to the critical role of postsynaptic Ca(2+) signals in dendritic development and synaptic plasticity, we tested whether long-term exposure to BDNF affects Ca(2+) elevations evoked by coincident excitatory postsynaptic potentials (EPSPs) and back-propagating action potentials (bAPs) in spiny dendrites of CA1 pyramidal neurons within hippocampal slice cultures. In control neurons, a train of 5 coincident EPSPs and bAPs evoked Ca(2+) elevations in oblique radial branches of the main apical dendrite that were of similar amplitude than those evoked by a train of 5 bAPs alone. On the other hand, dendritic Ca(2+) signals evoked by coincident EPSPs and bAPs were always larger than those triggered by bAPs in CA1 neurons exposed to BDNF for 48 h. This difference was not observed after blockade of NMDA receptors (NMDARs) with D,L-APV, but only in BDNF-treated neurons, suggesting that Ca(2+) signals in oblique radial dendrites include a synaptic NMDAR-dependent component. Co-treatment with the receptor tyrosine kinase inhibitor k-252a prevented the effect of BDNF on coincident dendritic Ca(2+) signals, suggesting the involvement of neurotrophin Trk receptors. These results indicate that long-term exposure to BDNF enhances Ca(2+) signaling during coincident pre- and postsynaptic activity in small spiny dendrites of CA1 pyramidal neurons, representing a potential functional consequence of neurotrophin-mediated dendritic remodeling in developing neurons.
Pozzo-Miller
Lucas
L
Department of Neurobiology and Civitan International Research Center, University of Alabama at Birmingham, 1825 University Blvd. Birmingham, AL 35294-2182, Alabama, USA. lucaspm@uab.edu
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001676:Biofeedback, Psychology / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects*; D002227:Carbazoles / Q000494:pharmacology; D003712:Dendrites / Q000187:drug effects*; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D006624:Hippocampus / Q000166:cytology*; D026121:Indole Alkaloids; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques / Q000379:methods; D017966:Pyramidal Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D026121:Indole Alkaloids; D015763:2-Amino-5-phosphonovalerate; C049985:staurosporine aglycone