PAIRING THE CHOLINERGIC AGONIST CARBACHOL WITH PATTERNED SCHAFFER COLLATERAL STIMULATION INITIATES PROTEIN-SYNTHESIS IN HIPPOCAMPAL CA1 PYRAMIDAL CELL DENDRITES VIA A MUSCARINIC, NMDA-DEPENDENT MECHANISM

被引:0
作者
FEIG, S
LIPTON, P
机构
[1] UNIV WISCONSIN,SCH MED,DEPT PHYSIOL,1300 UNIV AVE,MADISON,WI 53706
[2] UNIV WISCONSIN,SCH MED,DEPT ANAT,MADISON,WI 53706
[3] UNIV WISCONSIN,SCH MED,CTR NEUROSCI,MADISON,WI 53706
关键词
ACH; DENDRITES; HIPPOCAMPUS; LEARNING; NMDA; PROTEIN SYNTHESIS;
D O I
暂无
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Effects of afferent stimulation on local synthesis of protein in CA1 pyramidal cell dendrites were studied using light microscope autoradiography. Tissue was fixed with paraformaldehyde immediately after 3 min exposure to H-3-leucine in order to trap H-3 associated with macromolecules. The rate of H-3-leucine incorporation into dendrites of resting hippocampal slices was 10% the rate of incorporation into cell somata. Ninety percent of the incorporation into the somata was inhibited by cycloheximide (300 mum); none of the incorporation into dendrites was blocked by cycloheximide. Thus, there is no measurable extramitochondrial synthesis of protein in the dendrites of the resting slice. Slices were exposed to 50 mum carbachol and the Schaffer collateral afferents to the CA1 pyramidal cells were stimulated intermittently at 10 Hz over a 20 min period. In this case, H-3 incorporation into dendrites was increased almost threefold over resting levels, with no effect on label over the cell somata. There was no associated increase in uptake of free H-3-leucine, and the increase in label was completely blocked by cycloheximide. Thus, associating carbachol and afferent stimulation appears to activate de novo protein synthesis in the dendrites. Neither the carbachol alone nor the Schaffer collateral stimulation alone increased synthesis. The activation of dendrite synthesis was completely blocked by 5 mum atropine, and also by 50 muM D-aminophosphonovalerate. It did not occur when carbachol was paired with steady stimulation of the Schaffer collaterals at 1 Hz for 20 min, rather than with the patterned high-frequency stimulation. Thus, associating a cholinergic agonist with a level of neural activity that occurs in CA3 and CA 1 pyramidal cells during exploratory behavior (Muller et al., 1987) initiates local protein synthesis in target dendrites. This effect is dependent on muscarinic cholinergic receptors and NMDA-type glutamate receptors. The possible relationship of this phenomenon to mechanisms of learning is discussed.
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页码:1010 / 1021
页数:12
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