title: Activation of class I metabotropic glutamate receptors limits dendritic growth of Purkinje cells in organotypic slice cultures.
abstract: The development of the dendritic tree of a neuron is a complex process which is thought to be regulated strongly by signals from afferent fibers. We showed previously that the blockade of glutamatergic excitatory neurotransmission has little effect on Purkinje cell dendritic development. We have now studied the effects of glutamate receptor agonists on the development of Purkinje cell dendrites in mouse organotypic slice cultures. The activation of N-methyl-D-aspartate receptors had no major effect on Purkinje cell dendrites and the activation of (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid receptors was strongly excitotoxic so that no analysis of its effects on dendritic development was possible. The activation of metabotropic glutamate receptors led to a very strong inhibition of dendritic growth, resulting in Purkinje cells with very small stubby dendrites. This effect was specific for the activation of class I metabotropic glutamate receptors and could not be reduced by blocking synaptic transmission in the cultures, indicating that it was mediated by receptors present on Purkinje cells. Pharmacological experiments suggest that the signaling pathway involved does not require activation of phospholipase C or protein kinase C. The inhibition of dendritic growth by activation of class I metabotropic glutamate receptor could be a useful negative feedback mechanism for limiting the size of the dendritic tree of Purkinje cells after the establishment of a sufficient number of parallel fiber contacts. This developmental mechanism could protect Purkinje cells from excitotoxic death through excessive release of glutamate from an overload of parallel fiber contacts.
authors.affiliation: Anatomisches Institut, Universität Basel, Pestalozzistrasse 20, CH-4056 Basel, Switzerland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Sirzen-Zelenskaya
authors.forename: Judith
authors.initials: J
authors.lastname: Zeyse
authors.forename: Josef P
authors.initials: JP
authors.lastname: Kapfhammer
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D049108:Cell Enlargement / Q000187:drug effects; D002525:Cerebellar Cortex / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D006131:Growth Inhibitors / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D009924:Organ Culture Techniques; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D011689:Purkinje Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D010738:Type C Phospholipases / Q000187:drug effects / Q000378:metabolism
chemical_list: D018690:Excitatory Amino Acid Agonists; D006131:Growth Inhibitors; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D018698:Glutamic Acid; D011493:Protein Kinase C; D010738:Type C Phospholipases