Distally directed dendrotoxicity induced by kainic Acid in hippocampal interneurons of green fluorescent protein-expressing transgenic mice
| Autor: | Trang T. Lam, John W. Swann, Anthony A. Oliva |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Kainic acid
Green Fluorescent Proteins Excitotoxicity Kainate receptor Mice Transgenic Tetrodotoxin Hippocampal formation Biology In Vitro Techniques Inhibitory postsynaptic potential medicine.disease_cause Transfection Hippocampus Sodium Channels chemistry.chemical_compound Mice Interneurons medicine Excitatory Amino Acid Agonists Animals Receptors AMPA ARTICLE Kainic Acid Dose-Response Relationship Drug General Neuroscience Pyramidal Cells Glutamate receptor Lidocaine Neural Inhibition Dendrites Biolistics Iontophoresis Calcium Channel Blockers Luminescent Proteins medicine.anatomical_structure chemistry Ionotropic glutamate receptor Neuron Somatostatin Neuroscience Excitatory Amino Acid Antagonists Sodium Channel Blockers |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 22(18) |
| ISSN: | 1529-2401 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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