Homer 1a Suppresses Neocortex Long-Term Depression in a Cortical Layer-Specific Manner

• Published in: Journal of neurophysiology Vol. 99; no. 2; pp. 950 - 957
• Main Authors: Ueta, Yoshifumi, Yamamoto, Ryo, Sugiura, Shigeki, Inokuchi, Kaoru, Kato, Nobuo
• Format: Journal Article
• Language: English
• Published: United States Am Phys Soc 01.02.2008
• Subjects: 2-Amino-5-phosphonovalerate - pharmacology; Animals; Animals, Newborn; Carrier Proteins - pharmacology; Dose-Response Relationship, Radiation; Electric Stimulation - methods; Electroshock - methods; Excitatory Amino Acid Antagonists - pharmacology; Fibrinolytic Agents - pharmacology; Heparin - pharmacology; Homer Scaffolding Proteins; In Vitro Techniques; Long-Term Synaptic Depression - drug effects; Long-Term Synaptic Depression - physiology; Long-Term Synaptic Depression - radiation effects; Pyramidal Cells - drug effects; Pyramidal Cells - physiology; Pyramidal Cells - radiation effects; Pyridines - pharmacology; Rats; Rats, Wistar; Visual Cortex - cytology; Visual Cortex - drug effects
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.01101.2007

1 Department of Physiology, Kanazawa Medical University, Ishikawa; 2 Department of Integrative Brain Science, Kyoto University Graduate School of Medicine, Kyoto; 3 Medical Genetics Research Center, Nara Medical University, Nara; and 4 Mitsubishi Kagaku Institute of Life Sciences (MITILS), Tokyo, Japan Submitted 3 October 2007; accepted in final form 5 December 2007 Homer1a/Vesl-1S is an activity-dependently induced member of the scaffold protein family Homer/Vesl, which is known to link group I metabotropic glutamate receptors (mGluRs) to endoplasmic calcium release channels and to regulate them. Here we studied roles of Homer 1a in inducing long-term depression (LTD) in rat visual cortex slices. Homer 1a protein was injected by diffusion from whole cell patch pipettes. In layer VI pyramidal cells, LTD was reduced in magnitude with Homer 1a. LTD in layer VI was suppressed by applying antagonists of mGluR5, a subtype of group I mGluRs expressed with higher density than mGluR1 in neocortex pyramidal cells, or inositol-1,4,5-triphosphate receptors (IP3Rs) but not that against N -methyl- D -aspartate receptors (NMDARs). In layer II/III or layer V, Homer 1a injection was unable to affect LTD, which is mostly dependent on NMDARs and not on group I mGluRs in these layers. To examine the effects of endogenous Homer 1a, electroconvulsive shock (ECS) was applied. Homer 1a thereby induced, as did Homer 1a injection, reduced LTD magnitude in layer VI pyramidal cells and failed to do so in layer II/III or layer V pyramidal cells. These results indicate that both exo- and endogenous Homer 1a suppressed LTD in a cortical layer-specific manner, and its layer-specificity may be explained by the high affinity of Homer 1a to group I mGluRs. Address for reprint requests and other correspondence: N. Kato, Dept. of Physiology, Kanazawa Medical University, 920-0293 Ishikawa, Japan (E-mail: kato{at}kanazawa-med.ac.jp )