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The Journal of Neuroscience, September 15, 2002, 22(18):8052-8062
Distally Directed Dendrotoxicity Induced by Kainic Acid in
Hippocampal Interneurons of Green Fluorescent Protein-Expressing
Transgenic Mice
Anthony A.
Oliva Jr1, 2,
Trang T.
Lam1, 3, and
John
W.
Swann1, 2, 3
1 The Cain Foundation Laboratories,
2 Division of Neuroscience, and 3 Department of
Pediatrics, Baylor College of Medicine, Houston, Texas 77030
Excitotoxicity, resulting from the excessive release of glutamate,
is thought to contribute to a variety of neurological disorders, including epilepsy. Excitotoxic damage to dendrites, i.e.,
dendrotoxicity, is often characterized by the formation of large
dendritic swellings, or "beads." Here, we show that hippocampal
interneurons that express the neuropeptide somatostatin are highly
vulnerable to the excitotoxic effects of the ionotropic glutamate
receptor agonist kainate. Brief, focal iontophoretic application of
kainate rapidly induced bead formation in dendrites of
somatostatinergic interneurons that express green fluorescent protein
(GFP) from mice of the transgenic line GIN (GFP-expressing inhibitory
neurons). Surprisingly, beads often did not form at the site of
kainate application or even in the dendritic segment to which kainate
was applied; instead, dendritic beading occurred more distally, often
encompassing all branches distal to the application site. We have
termed this phenomena, "distally directed dendrotoxicity." Distally
directed beading was induced regardless of the branch order of the site
of application and was found to be dependent on activation of
voltage-gated sodium channels. Subsequent to induction, distally
directed beading would reverse in most cells; in other cells, however,
beading irreversibly invaded proximal dendritic segments and gradually
encompassed the entire dendritic tree. These results demonstrate that
distal dendritic segments are highly vulnerable to excitotoxic injury and imply that excessive excitatory activity originating in one synaptic pathway can impact synapses at more distal dendritic segments
of the same neuron. The discovery of this phenomenon will likely be
important in understanding interneuronal dysfunction following
excitotoxic injury.
Key words:
GABAergic neurons; interneurons; green fluorescent
protein; GFP; transgenic mice; hippocampus; somatostatin; explant; organotypic; dendrotoxicity; excitotoxicity; neurotoxicity; kainate; kainic acid; dendrite; sodium; sodium channel; tetrodotoxin; lidocaine; confocal microscopy; fluorescence microscopy; beading; bead
Copyright © 2002 Society for Neuroscience 0270-6474/02/22188052-11$05.00/0
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