Eighth nerve activity regulates intracellular calcium concentration of avian cochlear nucleus neurons via a metabotropic glutamate receptor.
1. Neurons in the cochlear nucleus, nucleus magnocellularis (NM), of embryonic and neonatal chicks are dependent on eighth nerve activity for their maintenance and survival. Removing this input results in the death of 20-40% of the NM neurons and profound changes in the morphology and metabolism of surviving neurons. 2. One of the first changes in NM neurons after an in vivo cochlea removal is an increase in intracellular calcium concentration ([Ca2+]i). Increased [Ca2+]i has been implicated in a number of neuropathologic conditions. 3. In this study, we orthodromically and antidromically stimulated NM neurons in an in vitro brain stem slice preparation and monitored NM field potentials while simultaneously assessing the [Ca2+]i of NM neurons using fura-2. 4. During continuous orthodromic stimulation, [Ca2+]i of NM neurons remained constant at 80 nM. In the absence of stimulation, NM neuron [Ca2+]i increased steadily to 230 nM by 90 min. Antidromic and contralateral stimulation produced a [Ca2+]i increase in NM neurons that was similar in magnitude but slightly more rapid than that observed in the absence of stimulation. 5. Addition of the metabotropic glutamate receptor (mGluR) antagonists (R,S)-alpha-methyl-4-carboxyphenylglycine or 2-amino-3-phosphonopropionic acid to the superfusate during continued orthodromic stimulation resulted in a dose-dependent, rapid, and dramatic increase in NM neuron [Ca2+]i without affecting the postsynaptic field potentials recorded from NM. 6. The ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione and 2-amino-5-phosphonovalerate eliminated NM field potentials during continued orthodromic stimulation but did not result in an increase in [Ca2+]i. 7. Continuous superfusion of trans-(+/-)-aminocyclopentane dicarboxylate, but not glutamate, prevented the increase in [Ca2+]i in the absence of stimulation. 8. These results suggest that NM neurons rely on eighth nerve activity-dependent activation of a mGluR to maintain physiological [Ca2+]i. Removal of this mGluR activation results in an increase in [Ca2+]i that may contribute to the early stages of degeneration and eventual death of these neurons.
Zirpel
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Virginia Merrill Bloedel Hearing Research Center, University of Washington School of Medicine, Seattle 98195-7923, USA.
Rubel
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D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002642:Chick Embryo; D017626:Cochlear Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004558:Electric Stimulation; D005072:Evoked Potentials, Auditory / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000502:physiology*; D000159:Vestibulocochlear Nerve / Q000187:drug effects / Q000502:physiology*
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D005456:Fluorescent Dyes; D017470:Receptors, Glutamate; D018094:Receptors, Metabotropic Glutamate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D002118:Calcium; D016257:Fura-2