Antisense DNA against calcineurin facilitates memory in contextual fear conditioning by lowering the threshold for hippocampal long-term potentiation induction

Learning and memory as well as long-term potentiation (LTP) depend on Ca2+ influx through the NMDA-type glutamate receptor (NMDAR) and the resulting activation of the Ca2+ and calmodulin-dependent protein kinase (CaMKII). Ca2+ influx via the NMDAR triggers CaMKII binding to the NMDAR for enhanced CaMKII accumulation at post-synaptic sites that experience heightened activity as occurring during LTP. Previously, we generated knock-in (KI) mice in which we replaced two residues in the NMDAR GluN2B subunit to impair CaMKII binding to GluN2B. Various forms of LTP at the Schaffer collateral synapses in CA1 are reduced by 50%. Nevertheless, working memory in the win-shift 8 arm maze and learning of the Morris water maze (MWM) task was normal in the KI mice although recall of the task was impaired in these mice during the period of early memory consolidation. We now show that massed training in the MWM task within a single day resulted in impaired learning. However, learning and recall of the Barnes maze task and contextual fear conditioning over one or multiple days were surprisingly unaffected. The differences observed in the MWM compared to the Barnes maze and contextual fear conditioning suggest a differential involvement of CaMKII and the specific interaction with GluN2B, probably depending on varying degrees of stress, cognitive demand or even potentially different plasticity mechanisms associated with the diverse tasks.

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Improved learning and memory of contextual fear conditioning and hippocampal CA1 long-term potentiation in histidine decarboxylase knock-out mice

Hippocampus ◽

10.1002/hipo.20305 ◽

2007 ◽

Vol 17 (8) ◽

pp. 634-641 ◽

Cited By ~ 37

Author(s):

Luying Liu ◽

Shihong Zhang ◽

Yongping Zhu ◽

Qiuli Fu ◽

Yuanyuan Zhu ◽

...

Keyword(s):

Histidine Decarboxylase ◽

Long Term Potentiation ◽

Contextual Fear Conditioning ◽

Knock Out ◽

Contextual Fear ◽

Term Potentiation ◽

Hippocampal Ca1 ◽

Improved Learning ◽

Knock Out Mice

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Adult Neurogenesis Conserves Hippocampal Learning Capacity

10.1101/200253 ◽

2017 ◽

Author(s):

Md Jahangir Alam ◽

Takashi Kitamura ◽

Yoshito Saitoh ◽

Noriaki Ohkawa ◽

Takashi Kondo ◽

...

Keyword(s):

Adult Neurogenesis ◽

Long Term Potentiation ◽

Underlying Mechanism ◽

Contextual Fear Conditioning ◽

Contextual Fear ◽

X Ray ◽

Learning Capacity ◽

Term Potentiation ◽

Memory Circuits

AbstractMemory coding strengthens synaptic efficacy in the hippocampus via a long-term potentiation (LTP)-like mechanism. Given that animals are able to store memories of everyday experiences, hippocampal circuits should be able to avoid saturation of overall synaptic weight to preserve learning capacity. However, the underlying mechanism for this is still poorly understood. Here, we show that adult neurogenesis in rats plays a crucial role in the maintenance of the hippocampal learning capacity for learning. Artificial saturation with hippocampal LTP impaired learning capacity in contextual fear conditioning, which then completely recovered after 14 days, when LTP had decayed to the basal level. Ablation of neurogenesis by X-ray irradiation delayed the recovery of learning capacity, while enhancement of neurogenesis using running wheel sped up the recovery. Thus, one benefit of ongoing adult neurogenesis is the maintenance of hippocampal learning capacity through homeostatic renewing of hippocampal memory circuits. Decreased neurogenesis in aged animals may underlie declines in cognitive function with aging.

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