Age-related enhancement of a protein synthesis-dependent late phase of LTP induced by low frequency paired-pulse stimulation in hippocampus.
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.
Huang
Yan-You
YY
Kavli Institute for Brain Science, New York, New York, USA.
Kandel
Eric R
ER
D000375:Aging / Q000502:physiology*; D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014176:Protein Biosynthesis / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology
D015220:Calcium Channels; D016194:Receptors, N-Methyl-D-Aspartate