PERSISTENT LONG TERM DEPRESSION IN YOUNG CA3-CA1 SYNAPSES FROM VGLUT2DEFICIENT MICE IMPAIRS SYNAPTIC REFINEMENT AND SPATIAL LEARNING IN ADULTS
Document Type
Presentation
Start Date
22-10-2010 1:30 PM
End Date
22-10-2010 1:45 PM
Description
It is known that VGLUT1 and VGLUT2 display complimentary distribution in the brain, with VGLUT1 predominant in cortex and hippocampus and VGLUT2 mainly in subcortical areas. However, during postnatal development, VGLUT2 is transiently expressed in cortical pyramidal neurons for unknown reasons. Here, we have generated conditional VGLUT2-deficient mice and targeted deletion of VGLUT2 to cortical-limbic areas of the developing brain using by Emx1 ere knockin mice. Using electrophysiological field recordings, we find an impaired LTD (but intact LTP), a reduction in basal transmission and increased paired-pulse ration (PPR) in young (P1214) CA3-CA1 synapses. In adult mice, we also find a reduction in basal transmission but an impaired L TP (with unchanged LTD). We used the Golgi-Cox method to assess dendrite morphology and find reductions in the total number of spines and in the density of spines per unit length of dendrite. In addition, while dendritic segments are as numerous as controls, these do not extent to normal lengths when the level of VGLUT2 is reduced. Morris water maze was used to assess hippocampal-dependent spatial memory in adult wild type and VGLUT2-deficient mice. We find that VGLUT2-deficient mice exhibited a loss of spatial learning but no differences in swimming speeds. We conclude that VGLUT2-encoded synaptic vesicles have high release probability in pyramidal neurons that contribute to mechanisms of LTD induction in young mice. We propose that the loss of VGLUT2 in cortical-limbic circuits results in persistent LTD during the critical developmental window of functional maturation of CA3-CA1 connections and results in excessive synaptic pruning and impaired spine formation, reduced LTP, and impaired spatial learning in adult.
Recommended Citation
He, Hongbo; Mahnke, A. H.; Doyle, S.; and Fan, N., "PERSISTENT LONG TERM DEPRESSION IN YOUNG CA3-CA1 SYNAPSES FROM VGLUT2DEFICIENT MICE IMPAIRS SYNAPTIC REFINEMENT AND SPATIAL LEARNING IN ADULTS" (2010). Dr. Joseph M. Moerschbaecher, III Graduate Research Day. 3.
https://digitalscholar.lsuhsc.edu/grad_rs/2010/presentation2/3
PERSISTENT LONG TERM DEPRESSION IN YOUNG CA3-CA1 SYNAPSES FROM VGLUT2DEFICIENT MICE IMPAIRS SYNAPTIC REFINEMENT AND SPATIAL LEARNING IN ADULTS
It is known that VGLUT1 and VGLUT2 display complimentary distribution in the brain, with VGLUT1 predominant in cortex and hippocampus and VGLUT2 mainly in subcortical areas. However, during postnatal development, VGLUT2 is transiently expressed in cortical pyramidal neurons for unknown reasons. Here, we have generated conditional VGLUT2-deficient mice and targeted deletion of VGLUT2 to cortical-limbic areas of the developing brain using by Emx1 ere knockin mice. Using electrophysiological field recordings, we find an impaired LTD (but intact LTP), a reduction in basal transmission and increased paired-pulse ration (PPR) in young (P1214) CA3-CA1 synapses. In adult mice, we also find a reduction in basal transmission but an impaired L TP (with unchanged LTD). We used the Golgi-Cox method to assess dendrite morphology and find reductions in the total number of spines and in the density of spines per unit length of dendrite. In addition, while dendritic segments are as numerous as controls, these do not extent to normal lengths when the level of VGLUT2 is reduced. Morris water maze was used to assess hippocampal-dependent spatial memory in adult wild type and VGLUT2-deficient mice. We find that VGLUT2-deficient mice exhibited a loss of spatial learning but no differences in swimming speeds. We conclude that VGLUT2-encoded synaptic vesicles have high release probability in pyramidal neurons that contribute to mechanisms of LTD induction in young mice. We propose that the loss of VGLUT2 in cortical-limbic circuits results in persistent LTD during the critical developmental window of functional maturation of CA3-CA1 connections and results in excessive synaptic pruning and impaired spine formation, reduced LTP, and impaired spatial learning in adult.
Comments
See abstract book page 39