So you think LTP is meaningless?
LTP was reported by Bliss and over 30 years ago now. Even though many labs have studied the process, there is a great deal of cynicism from many quarters about the phenomenon. The nay-sayers have often said there is no real evidence that LTP actually has anything to with memory. A paper (Science (2003) 299: 1585-8) from the Malinow lab goes some way to contradict such an idea. In a characteristically elegant series of experiments the Malinow shows that significant experience does indeed induce LTP in vivo in rodents.
They use whisker plucking as the means to deprive neurons of experience. Thus, they injected DNA for one subunit of the AMPA-R (which was also tagged with GFP to guide patching, “GluR1-GFP”) at PND 12 into the barrel cortex of mice. At PND 14 they made acute slices to test for LTP in the usual way. Since not all neurons become transfected in vivo, they have convenient in-built control neurons to give them the % rectification, along with ipsi/contralteral control populations of cells as well (transfection with GFP alone had no effect). The Malinow lab found that mice without whisker trimming (“intact”) had populations of neurons that were rectified. This was the case with whisker-trimmed animals (“deprived”) only when they analyzed ipsilateral neurons; contralateral neurons showed no rectification. Thus, significant sensory experience for the mouse (whiskers are very important for rodents’ life) increases synaptic strength. This finding was substantiated and embellished by several more experiments: (1) transfection with the cytoplasmic tail of AMPA GluR1 blocked LTP in intact but not deprived animals [ Fig 2]; (2) GluR1-GFP could be replaced by GluR2 if intact animals from PND 12 to 14 were then rendered deprived for 1 day subsequently [Fig. 3]; (3) Previously the Malinow lab had developed a very clever way of using electrophysiological tagging to assay if APMA receptors become incorporated into synapses in slices (R586Q mutant). They made a mutant channel that works in a slightly different way from endogenous receptors. Transfection of animals with GluR2-R586-GFP along with a GluR2 cytoplasmic tail showed that experience was not necessary to block GluR2 incorporation [Fig. 4]. Thus, sensory input does give rise to LTP. Perhaps it is worth studying after all.
LTP was reported by Bliss and over 30 years ago now. Even though many labs have studied the process, there is a great deal of cynicism from many quarters about the phenomenon. The nay-sayers have often said there is no real evidence that LTP actually has anything to with memory. A paper (Science (2003) 299: 1585-8) from the Malinow lab goes some way to contradict such an idea. In a characteristically elegant series of experiments the Malinow shows that significant experience does indeed induce LTP in vivo in rodents.
They use whisker plucking as the means to deprive neurons of experience. Thus, they injected DNA for one subunit of the AMPA-R (which was also tagged with GFP to guide patching, “GluR1-GFP”) at PND 12 into the barrel cortex of mice. At PND 14 they made acute slices to test for LTP in the usual way. Since not all neurons become transfected in vivo, they have convenient in-built control neurons to give them the % rectification, along with ipsi/contralteral control populations of cells as well (transfection with GFP alone had no effect). The Malinow lab found that mice without whisker trimming (“intact”) had populations of neurons that were rectified. This was the case with whisker-trimmed animals (“deprived”) only when they analyzed ipsilateral neurons; contralateral neurons showed no rectification. Thus, significant sensory experience for the mouse (whiskers are very important for rodents’ life) increases synaptic strength. This finding was substantiated and embellished by several more experiments: (1) transfection with the cytoplasmic tail of AMPA GluR1 blocked LTP in intact but not deprived animals [ Fig 2]; (2) GluR1-GFP could be replaced by GluR2 if intact animals from PND 12 to 14 were then rendered deprived for 1 day subsequently [Fig. 3]; (3) Previously the Malinow lab had developed a very clever way of using electrophysiological tagging to assay if APMA receptors become incorporated into synapses in slices (R586Q mutant). They made a mutant channel that works in a slightly different way from endogenous receptors. Transfection of animals with GluR2-R586-GFP along with a GluR2 cytoplasmic tail showed that experience was not necessary to block GluR2 incorporation [Fig. 4]. Thus, sensory input does give rise to LTP. Perhaps it is worth studying after all.
posted by graham at 3:34 PM
0 Comments:
Post a Comment
<< Home