Post on 18-Mar-2016
description
Optical controlling reveals time-dependent roles for adult-born
dentate granule cellsYan Gu, Maithe Arruda-Carvalho, Jia Wang, Stephen
R Janoschka, Sheena A Josselyn,Paul W Frankland & Shaoyu Ge
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Background
The adult hippocampus continues to give rise to several thousand new dentate granule cells everyday.
Studies using global perturbation or ablation of adult hippocampal neurogenesis has revealed deficits in some forms of hippocampal memory.
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As the morphological and physiological phenotypes of adult-born cells change markedly as they mature, they may have distinct roles at different stages following integration into hippocampal circuits.
Adult-born dentate granule cells (DGCs) extend dendrites receive functional input from the existing neural circuits as early as 2 weeks after birth.
Input (dendritic) synapses of adult-born neurons show enhanced plasticity between 4–6 weeks after birth compared with other stages.
Background
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What is the precise timing for these adult-born functional output synapse formation and maturation?
Whether do output synapses, if formed and functional, also exhibit heightened plasticity around the same time?
What is its functional role?
Questions
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Methods
Optogenetic stimulation
Water mazeClassical fear conditioning
Retroviral birth-dating + Gene delivery(EGFP+ Light gated ion channels)
Electrophysiological experiments
Behavioral experiments
Synaptic transmission efficiency, Capability of LTP
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Results
Birth-dating and labeling newborn DGCs
Experimental timeline
Labeling specificity of newborn DGCs with high-titer retrovirusNo mature DGC-like cells at 1 and 2 wpi
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Results
Adult-born DGCs fully integrate into the hippocampal trisynaptic circuits by ~4 wpi
Adult-born neurons form functional synapses on CA3 pyramidal neurons
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Results
Heightened synaptic plasticity of young adult-born neurons
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Results
Output synapses of mature newborn DGCs remain plastic, but have a higher induction threshold
Young newborn neurons exhibit heightened plasticity that peaks at ~4 wpi9
Conclusion 1
• Adult-born DGCs fully incorporate into the hippocampal trisynaptic neural circuit around 4 wpi and DGCs at this age have more excitable membranes and enhanced input/output synaptic plasticity.
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ResultsOptical silencing of newborn DGCs does not
influence acquisition of spatial memory
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ResultsSilencing young newborn neurons affects
spatial memory retrieval
labeled ~4-week-old adult-born DGCs regulate spatial memory retrieval. 12
ResultsSilencing young newborn neurons impairs
retrival of contextural fear memory
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ResultsThe behavioral role for newborn DGCs relies on their age
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Results
Heightened plasticity in young newborn neurons may be important for memory retrieval
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Results
Silencing newborn neurons at 4 wpi, but not 8 wpi, disrupted memory retrieval in both tasks
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Conclusion 2
• Adult-born neurons may be transiently critical for memory retrieval, but the effect, at least in spatial and contextual memory retrieval, may decline as these adult-born neurons continue to mature.
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Thank you
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