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Blocking brain‐derived neurotrophic factor inhibits injury‐induced hyperexcitability of hippocampal CA 3 neurons
Author(s) -
Gill Raminder,
Chang Philip K.Y.,
Prenosil George A.,
Deane Emily C.,
McKinney Rebecca A.
Publication year - 2013
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12367
Subject(s) - tropomyosin receptor kinase b , neuroscience , hippocampal formation , neurotrophic factors , brain derived neurotrophic factor , neurotrophin , hippocampus , sprouting , schaffer collateral , excitatory postsynaptic potential , biology , inhibitory postsynaptic potential , medicine , receptor , botany
Brain trauma can disrupt synaptic connections, and this in turn can prompt axons to sprout and form new connections. If these new axonal connections are aberrant, hyperexcitability can result. It has been shown that ablating tropomyosin‐related kinase B ( T rk B ), a receptor for brain‐derived neurotrophic factor ( BDNF ), can reduce axonal sprouting after hippocampal injury. However, it is unknown whether inhibiting BDNF ‐mediated axonal sprouting will reduce hyperexcitability. Given this, our purpose here was to determine whether pharmacologically blocking BDNF inhibits hyperexcitability after injury‐induced axonal sprouting in the hippocampus. To induce injury, we made S chaffer collateral lesions in organotypic hippocampal slice cultures. As reported by others, we observed a 50% reduction in axonal sprouting in cultures treated with a BDNF blocker ( T rk B ‐ F c) 14 days after injury. Furthermore, lesioned cultures treated with T rk B ‐ F c were less hyperexcitable than lesioned untreated cultures. Using electrophysiology, we observed a two‐fold decrease in the number of CA 3 neurons that showed bursting responses after lesion with T rk B ‐ F c treatment, whereas we found no change in intrinsic neuronal firing properties. Finally, evoked field excitatory postsynaptic potential recordings indicated an increase in network activity within area CA 3 after lesion, which was prevented with chronic T rk B ‐ F c treatment. Taken together, our results demonstrate that blocking BDNF attenuates injury‐induced hyperexcitability of hippocampal CA 3 neurons. Axonal sprouting has been found in patients with post‐traumatic epilepsy. Therefore, our data suggest that blocking the BDNF –TrkB signaling cascade shortly after injury may be a potential therapeutic target for the treatment of post‐traumatic epilepsy.