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Dopamine-dependent facilitation of LTP induction in hippocampal CA1 by exposure to spatial novelty

Abstract

In addition to its role in memory formation, the hippocampus may act as a novelty detector. Here we investigated whether attention to novel events can promote the associative synaptic plasticity mechanisms believed to be necessary for storing those events in memory. We therefore examined whether exposure to a novel spatial environment promoted the induction of activity-dependent persistent increases in glutamatergic transmission (long-term potentiation, LTP) at CA1 synapses in the rat hippocampus. We found that brief exposure to a novel environment lowered the threshold for the induction of LTP. This facilitatory effect was present for a short period following novelty exposure but was absent in animals that explored a familiar environment. Furthermore, the facilitation was dependent on activation of D1/D5 receptors. These findings support an important role for dopamine-regulated synaptic plasticity in the storage of unpredicted information in the CA1 area.

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Figure 1: Exposure to a novel environment facilitates the induction of LTP at hippocampal CA1 synapses in freely behaving rats.
Figure 2: Time window for facilitated induction of LTP by novelty exposure.
Figure 3: Dopamine-dependence of the facilitation of the induction of LTP by novelty exposure.
Figure 4: Pharmacological activation of D1/D5 dopamine receptors mimics the effect of novelty exploration on LTP induction.

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Acknowledgements

The authors wish to thank D. Balschun for help with the i.c.v. injection method. This research was funded by the Wellcome Trust, the Health Research Board of Ireland, Enterprise Ireland, the Irish Higher Education Authority (Programme for Research in Third-Level Institutions), European Union and Science Foundation Ireland.

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Correspondence to Michael J. Rowan.

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Li, S., Cullen, W., Anwyl, R. et al. Dopamine-dependent facilitation of LTP induction in hippocampal CA1 by exposure to spatial novelty. Nat Neurosci 6, 526–531 (2003). https://doi.org/10.1038/nn1049

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