Age-related enhancement of a protein synthesis-dependent late phase of LTP induced by low frequency paired-pulse stimulation in hippocampus
- Yan-You Huang2 and
- Eric R. Kandel1,2,3,4
Abstract
Protein synthesis-dependent late phase of LTP (L-LTP) is typically induced by repeated high-frequency stimulation (HFS). This form of L-LTP is reduced in the aged animal and is positively correlated with age-related memory loss. Here we report a novel form of protein synthesis-dependent late phase of LTP in the CA1 region of hippocampus induced by a brief 1-Hz paired-pulse stimulation (PP-1 Hz, 1 min). In contrast to L-LTP induced by HFS, the late phase of PP-1 Hz LTP does not exist in young adult animals. Rather, it emerges and becomes enhanced in an age-related way. Thus, in 1.5- to 2-mo-old mice, a brief PP-1 Hz stimulation induces only a short lasting LTP, decaying to baseline in about 90 min. By contrast, PP-1 Hz stimulation induces an enduring and protein synthesis dependent LTP in 12- to 18-mo-old mice. The PP-1 Hz-induced L-LTP is dependent on NMDA receptor activation, requires voltage-dependent calcium channels, and is modulated by dopamine D1/D5 receptors. Because memory ability declines with aging, the age-related enhancement of L-LTP induced by PP-1 Hz stimulation indicates that this form of L-LTP appears to be inversely correlated with memory ability.
Footnotes
- 4
↵4 Corresponding author.
↵4 E-mail ERK5{at}columbia.edu; fax (212) 543-5474.
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Article and publication are at http://www.learnmem.org/cgi/doi/10.1101/lm.166906
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- Received December 14, 2005.
- Accepted February 21, 2006.
- Cold Spring Harbor Laboratory Press