PMID- 12843269 OWN - NLM STAT- MEDLINE DCOM- 20030814 LR - 20200225 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 23 IP - 13 DP - 2003 Jul 2 TI - Brain-derived neurotrophic factor mediates activity-dependent dendritic growth in nonpyramidal neocortical interneurons in developing organotypic cultures. PG - 5662-73 AB - Brain-derived neurotrophic factor (BDNF) promotes postnatal maturation of GABAergic inhibition in the cerebral and cerebellar cortices, and its expression and release are enhanced by neuronal activity, suggesting that it acts in a feedback manner to maintain a balance between excitation and inhibition during development. BDNF promotes differentiation of cerebellar, hippocampal, and neostriatal inhibitory neurons, but its effects on the dendritic development of neocortical inhibitory interneurons remain unknown. Here, we show that BDNF mediates depolarization-induced dendritic growth and branching in neocortical interneurons. To visualize inhibitory interneurons, we biolistically transfected organotypic cortical slice cultures from neonatal mice with green fluorescent protein (GFP) driven by the glutamic acid decarboxylase (GAD)67 promoter. Nearly all GAD67-GFP-expressing neurons were nonpyramidal, many contained GABA, and some expressed markers of neurochemically defined GABAergic subtypes, indicating that GAD67-GFP-expressing neurons were GABAergic. We traced dendritic trees from confocal images of the same GAD67-GFP-expressing neurons before and after a 5 d growth period, and quantified the change in total dendritic length (TDL) and total dendritic branch points (TDBPs) for each neuron. GAD67-GFP-expressing neurons growing in control medium exhibited a 20% increase in TDL, but in 200 ng/ml BDNF or 10 mm KCl, this increase nearly doubled and was accompanied by a significant increase in TDBPs. Blocking action potentials with TTX did not prevent the BDNF-induced growth, but antibodies against BDNF blocked the growth-promoting effect of KCl. We conclude that BDNF, released by neocortical pyramidal neurons in response to depolarization, enhances dendritic growth and branching in nearby inhibitory interneurons. FAU - Jin, Xiaoming AU - Jin X AD - Department of Neurobiology and Anatomy, West Virginia University, Morgantown, West Virginia 26506-9128, USA. FAU - Hu, Hang AU - Hu H FAU - Mathers, Peter H AU - Mathers PH FAU - Agmon, Ariel AU - Agmon A LA - eng GR - R01 EY012152/EY/NEI NIH HHS/United States GR - R29 EY012152/EY/NEI NIH HHS/United States GR - EY12152/EY/NEI NIH HHS/United States GR - HD33463/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Isoenzymes) RN - 0 (Luminescent Proteins) RN - 0 (Nerve Growth Factors) RN - 145172-44-7 (neurotrophin 5) RN - 147336-22-9 (Green Fluorescent Proteins) RN - 56-12-2 (gamma-Aminobutyric Acid) RN - EC 4.1.1.15 (Glutamate Decarboxylase) RN - EC 4.1.1.15 (glutamate decarboxylase 1) RN - P658DCA9XD (neurotrophin 4) SB - IM MH - Animals MH - Animals, Newborn MH - Biolistics MH - Brain-Derived Neurotrophic Factor/antagonists & inhibitors/pharmacology/*physiology MH - Cell Division/drug effects/physiology MH - Cells, Cultured MH - Dendrites/drug effects/*physiology MH - Glutamate Decarboxylase/genetics MH - Green Fluorescent Proteins MH - Immunohistochemistry MH - In Vitro Techniques MH - Interneurons/cytology/drug effects/*physiology MH - Isoenzymes/genetics MH - Luminescent Proteins/biosynthesis/genetics MH - Mice MH - Neocortex/cytology/*growth & development/*physiology MH - Nerve Growth Factors/pharmacology MH - Neural Inhibition/physiology MH - Promoter Regions, Genetic MH - Time Factors MH - gamma-Aminobutyric Acid/metabolism PMC - PMC6741232 EDAT- 2003/07/05 05:00 MHDA- 2003/08/15 05:00 PMCR- 2004/01/02 CRDT- 2003/07/05 05:00 PHST- 2003/07/05 05:00 [pubmed] PHST- 2003/08/15 05:00 [medline] PHST- 2003/07/05 05:00 [entrez] PHST- 2004/01/02 00:00 [pmc-release] AID - 23/13/5662 [pii] AID - 10.1523/JNEUROSCI.23-13-05662.2003 [doi] PST - ppublish SO - J Neurosci. 2003 Jul 2;23(13):5662-73. doi: 10.1523/JNEUROSCI.23-13-05662.2003.