Regulation of the activity of hippocampal stratum oriens interneurons by α7 nicotinic acetylcholine receptors
Section snippets
Whole-cell recording
Housing and treatment of all animals were in accordance with protocols approved by the University of Colorado Animal Care and Use Committee, and were designed to minimize any animal suffering as well as the number of animals used in this study. Unanesthetized young (18–27 day old) male Sprague–Dawley rats (Charles River Laboratories, Wilmington, MA, USA) were decapitated and 300 μM thick coronal slices were made of their hippocampi using a Vibratome (Pelco, Ted Pella, Redding, CA, USA). Slices
Stratum oriens interneurons respond to ACh application with nAChR-mediated responses
Brief pressure application of ACh to the cell bodies of visually identified interneurons in stratum oriens elicited fast inward currents in 49 out of 61 cells tested under voltage clamp conditions. These responses were generally of large amplitude (−243±30 pA; n=49), decayed rapidly (Fig. 1A–D), and were uniformly blocked by bath application of the α7 nAChR selective antagonists MLA (75 nM; 95±3% block; n=9) or BTX (100 nM; 88±5% block; n=5). Antagonists selective for non-α7 nAChRs did not
Pharmacological characteristics of stratum oriens layer interneurons
Although most previous studies of nicotinic responses in hippocampal interneurons have focused on those located in stratum radiatum, the interneurons found in stratum oriens include subtypes that play unique roles in regulating hippocampal activity (Buckmaster and Soltesz, 1996, Freund and Buzsaki, 1996). Nevertheless, the present study has demonstrated that there are considerable similarities in the nicotinic responsiveness of interneurons in the stratum oriens and stratum radiatum. Both the
Conclusion
These experiments demonstrate that most major anatomical subtypes of inhibitory cells in the CA1 stratum oriens respond to pressure application of ACh with α7 nAChR-mediated responses. This suggests that alterations in nicotinic function in the hippocampus could have a substantial impact on synaptic inhibition through activation of several major classes of GABAergic interneurons. Furthermore, the rapid desensitization of α7 nAChR currents that has been described in various systems plays a
Note added in proof
Tom Dunwiddie, scientist, mentor and friend, was killed July 12th in a climbing accident in Yosemite National Park. We will miss him greatly.
Acknowledgements
We thank K. Svoboda for his assistance with electrophysiological techniques, and R. Levinson and R. Cloues for their assistance and use of equipment for the confocal imaging. We also thank C. Adams for expert technical assistance and insightful comments. This work was supported by the Veterans Administration Medical Research Service and by Grants MH44212 and MH61617 from the National Institute of Mental Health.
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