Objective: Assessment of contextual fear conditioning as a measure of hippocampal-dependent learning and memory, specifically to evaluate the contribution of adult-born hippocampal neurons to this behavior
Materials & Equipment Checklist
3 items3 from ConductScience
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Equipment3
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Protocol Steps
View Abstract
Although hippocampal neurogenesis has been described in many adult mammals, the functional impact of this process on physiology and behavior remains unclear. In the present study, we used two independent methods to ablate hippocampal neurogenesis and found that each procedure caused a limited behavioral deficit and a loss of synaptic plasticity within the dentate gyrus. Specifically, focal X irradiation of the hippocampus or genetic ablation of glial fibrillary acidic protein-positive neural progenitor cells impaired contextual fear conditioning but not cued conditioning. Hippocampal-dependent spatial learning tasks such as the Morris water maze and Y maze were unaffected. These findings show that adult-born neurons make a distinct contribution to some but not all hippocampal functions. In a parallel set of experiments, we show that long-term potentiation elicited in the dentate gyrus in the absence of GABA blockers requires the presence of new neurons, as it is eliminated by each of our ablation procedures. These data show that new hippocampal neurons can be preferentially recruited over mature granule cells in vitro and may provide a framework for how this small cell population can influence behavior.
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Hippocampal neurogenesis ablation - Method 1
Focal X irradiation of the hippocampus to ablate hippocampal neurogenesis
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Note: This is one of two independent methods used to ablate hippocampal neurogenesis
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“focal X irradiation of the hippocampus or genetic ablation of glial fibrillary acidic protein-positive neural progenitor cells impaired contextual fear conditioning”
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Hippocampal neurogenesis ablation - Method 2
Genetic ablation of glial fibrillary acidic protein-positive neural progenitor cells to ablate hippocampal neurogenesis
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Note: This is one of two independent methods used to ablate hippocampal neurogenesis
View evidence from paper
“focal X irradiation of the hippocampus or genetic ablation of glial fibrillary acidic protein-positive neural progenitor cells impaired contextual fear conditioning”
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Contextual fear conditioning
Subjects are exposed to a context paired with an unconditioned stimulus to assess hippocampal-dependent learning and memory
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Note: This task was impaired by both ablation procedures
View evidence from paper
“focal X irradiation of the hippocampus or genetic ablation of glial fibrillary acidic protein-positive neural progenitor cells impaired contextual fear conditioning but not cued conditioning.”
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Cued fear conditioning
Subjects are exposed to a cue paired with an unconditioned stimulus to assess non-hippocampal dependent learning
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Note: This task was NOT impaired by ablation procedures, indicating specificity of the effect
View evidence from paper
“focal X irradiation of the hippocampus or genetic ablation of glial fibrillary acidic protein-positive neural progenitor cells impaired contextual fear conditioning but not cued conditioning.”
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Morris water maze task
Hippocampal-dependent spatial learning task to assess spatial memory
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Note: This task was unaffected by ablation procedures
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“Hippocampal-dependent spatial learning tasks such as the Morris water maze and Y maze were unaffected.”
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Y maze task
Hippocampal-dependent spatial learning task to assess spatial memory
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Note: This task was unaffected by ablation procedures
View evidence from paper
“Hippocampal-dependent spatial learning tasks such as the Morris water maze and Y maze were unaffected.”
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Long-term potentiation recording in dentate gyrus
Electrophysiological assessment of synaptic plasticity in the dentate gyrus in vitro
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Note: Long-term potentiation elicited in the dentate gyrus in the absence of GABA blockers requires the presence of new neurons
View evidence from paper
“long-term potentiation elicited in the dentate gyrus in the absence of GABA blockers requires the presence of new neurons, as it is eliminated by each of our ablation procedures.”
Subjects / Specimens
Species
mouse
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Two independent ablation methods were used: focal X irradiation of hippocampus or genetic ablation of glial fibrillary acidic protein-positive neural progenitor cells
