The Journal of Neurophysiology Vol. 77 No. 4 April 1997, pp. 1889-1905
Copyright ©1997 The American Physiological Society

Evidence for Functional Metabotropic Glutamate Receptors in the Dorsal Cochlear Nucleus

Scott C. Molitor¹ and Paul B. Manis^{1, 2, 3}

¹ Department of Biomedical Engineering, ² Department of Neuroscience, and ³ Department of Otolaryngology, Head and Neck Surgery, and The Center for Hearing and Balance, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205

Molitor, Scott C. and Paul B. Manis. Evidence for functional metabotropic glutamate receptors in the dorsal cochlear nucleus. J. Neurophysiol. 77: 1889-1905, 1997. The parallel fibers (PFs) of the dorsal cochlear nucleus (DCN) molecular layer use glutamate as a neurotransmitter. Although metabotropic glutamate receptors (mGluRs) have been identified on cells postsynaptic to the PFs, little is known about the effects of mGluR activation in PF synaptic transmission in the DCN. To investigate these effects, PF-evoked field potentials were recorded from the DCN in guinea pig brain stem slice preparations. The -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated components of the field response were reversibly depressed by bathing the slice in the mGluR agonists (±)-aminocyclopentane-1,3-dicarboxylic acid (trans-ACPD) or (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD]. A similar depression was produced by the mGluR1/5 agonist (RS)-3,5-dihydroxyphenylglycine, but not by the mGluR2/3 agonist (2S,1S,2S)-2-(carboxycyclopropyl)glycine or by the mGluR4/6/7/8 agonist L(+)-2-amino-4-phosphonobutyric acid. In addition to the AMPA component, an N-methyl-D-aspartate (NMDA) receptor-dependent component of the field potentials could be identified when the slices were bathed in a low magnesium solution. Under these conditions, the ACPD-induced depression of the AMPA component did not completely recover, whereas the depression of the NMDA component usually recovered and potentiated in some slices. Intracellular recordings of PF-evoked responses were obtained to ascertain which neuronal populations were affected by mGluR activation. Activation of mGluRs produced a reversible depression of PF-evoked responses in cartwheel cells that was not accompanied by any changes in paired-pulse facilitation. The PF-evoked responses recorded from pyramidal cells were unaffected by mGluR activation. Both cell types exhibited a reversible depolarization during (1S,3R)-ACPD application. Subsequent experiments explored the involvement of protein kinases in mediating the effects of mGluRs. The protein kinase C (PKC) activator phorbol-12,13-diacetate partially inhibited the mGluR-mediated depression of the field response;however, the PKC inhibitor 2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)-maleimide or the protein kinaseA inhibitor N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide had little effect on the actions of (1S,3R)-ACPD. These results demonstrate that functional mGluRs are present at PF synapses and are capable of modulating PF synaptic transmission in the DCN.

This article has been cited by other articles:

				F. A. Ene, P. H. M. Kullmann, D. C. Gillespie, and K. Kandler Glutamatergic Calcium Responses in the Developing Lateral Superior Olive: Receptor Types and Their Specific Activation by Synaptic Activity Patterns J Neurophysiol, October 1, 2003; 90(4): 2581 - 2591. [Abstract] [Full Text] [PDF]

				K. Fujino and D. Oertel Bidirectional synaptic plasticity in the cerebellum-like mammalian dorsal cochlear nucleus PNAS, January 7, 2003; 100(1): 265 - 270. [Abstract] [Full Text] [PDF]

				J. A. Kaltenbach, J. D. Rachel, T. A. Mathog, J. Zhang, P. R. Falzarano, and M. Lewandowski Cisplatin-Induced Hyperactivity in the Dorsal Cochlear Nucleus and Its Relation to Outer Hair Cell Loss: Relevance to Tinnitus J Neurophysiol, August 1, 2002; 88(2): 699 - 714. [Abstract] [Full Text] [PDF]

				S. C. Molitor and P. B. Manis Voltage-Gated Ca2+ Conductances in Acutely Isolated Guinea Pig Dorsal Cochlear Nucleus Neurons J Neurophysiol, March 1, 1999; 81(3): 985 - 998. [Abstract] [Full Text] [PDF]

				D. H. Sanes, J. McGee, and E. J. Walsh Metabotropic Glutamate Receptor Activation Modulates Sound Level Processing in the Cochlear Nucleus J Neurophysiol, July 1, 1998; 80(1): 209 - 217. [Abstract] [Full Text] [PDF]