| Title: | Protein kinase Calpha mediates a novel form of plasticity in the accessory olfactory bulb |
| Author(s): | Dong C; Godwin DW; Brennan PA; Hegde AN; |
| Address: | "Department of Neurobiology and Anatomy, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157-0001, USA" |
| DOI: | 10.1016/j.neuroscience.2009.06.069 |
| ISSN/ISBN: | 1873-7544 (Electronic) 0306-4522 (Print) 0306-4522 (Linking) |
| Abstract: | "Modification of synapses in the accessory olfactory bulb (AOB) is believed to underlie pheromonal memory that enables mate recognition in mice. The memory, which is acquired with single-trial learning, forms only with coincident noradrenergic and glutamatergic inputs to the AOB. The mechanisms by which glutamate and norepinephrine (NE) alter the AOB synapses are not well understood. Here we present results that not only reconcile the earlier, seemingly contradictory, observations on the role of glutamate and NE in changing the AOB synapses, but also reveal novel mechanisms of plasticity. Our studies suggest that initially, glutamate acting at Group II metabotropic receptors and NE acting at alpha(2)-adrenergic receptors inhibit N-type and R-type Ca(2+) channels in mitral cells via a G-protein. The N-type and R-type Ca(2+) channel inhibition is reversed by activation of alpha(1)-adrenergic receptors and protein kinase Calpha (PKCalpha). Based on these results, we propose a hypothetical model for a new kind of synaptic plasticity in the AOB that accounts for the previous behavioral data on pheromonal memory. According to this model, initial inhibition of the Ca(2+) channels suppresses the GABAergic inhibitory feedback to mitral cells, causing disinhibition and Ca(2+) influx. NE also activates phospholipase C (PLC) through alpha(1)-adrenergic receptors generating inositol 1,4,5-trisphosphate and diacylglycerol (DAG). Calcium and DAG together activate PKCalpha which switches the disinhibition to increased inhibition of mitral cells. Thus, PKCalpha is likely to be a coincidence detector integrating glutamate and NE input in the AOB and bridging the short-term signaling to long-term structural changes resulting in enhanced inhibition of mitral cells that is thought to underlie memory formation" |
| Keywords: | "Animals Calcium/physiology Calcium Channels, N-Type/physiology Calcium Channels, R-Type/physiology Female GTP-Binding Proteins/physiology Glutamic Acid/pharmacology/physiology In Vitro Techniques Inhibitory Postsynaptic Potentials/drug effects Isoenzymes/;" |
| Notes: | "MedlineDong, C Godwin, D W Brennan, P A Hegde, A N eng R21 DC006856/DC/NIDCD NIH HHS/ R21 DC006856-01/DC/NIDCD NIH HHS/ R21DC006856/DC/NIDCD NIH HHS/ R21 EY018159/EY/NEI NIH HHS/ R21EY0018159/EY/NEI NIH HHS/ R21 DC006856-02/DC/NIDCD NIH HHS/ R01AA016852/AA/NIAAA NIH HHS/ R01 AA016852/AA/NIAAA NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2009/07/08 Neuroscience. 2009 Oct 20; 163(3):811-24. doi: 10.1016/j.neuroscience.2009.06.069. Epub 2009 Jul 4" |
