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ARTICLE

Mechanism of Cannabinoid Effects on Long-Term Potentiation and Depression in Hippocampal CA1 Neurons

Dinah L. Misner and Jane M. Sullivan
Journal of Neuroscience 15 August 1999, 19 (16) 6795-6805; https://doi.org/10.1523/JNEUROSCI.19-16-06795.1999
Dinah L. Misner
1Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, California 92037
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Jane M. Sullivan
1Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, California 92037
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Abstract

Cannabinoids, the active constituents of marijuana, are known to impair learning and memory. Receptors for cannabinoids are highly expressed in the hippocampus, a brain region that is believed to play an important role in certain forms of learning and memory. To investigate the possible contribution of cannabinoid receptor-mediated deficits in hippocampal function to the learning and memory impairments produced by marijuana, we studied the effects of cannabinoid receptor activation on two models of learning and memory, long-term potentiation (LTP) and long-term depression (LTD), in hippocampal slices. Although LTP and LTD of CA1 field potentials were blocked by cannabinoid receptor activation in the presence of Mg2+, they could be induced after Mg2+ was removed. Similarly, LTP and LTD of whole-cell EPSCs were unimpaired in the presence of cannabinoid receptor agonist when the postsynaptic membrane was depolarized during the LTP or LTD induction protocol. Cannabinoid receptor activation also reduced EPSCs and enhanced paired-pulse facilitation, while having no effect on the amplitude of spontaneous miniature EPSCs. Finally, as with cannabinoid receptor activation, inhibition of LTP by adenosine receptor activation could be overcome by removal of Mg2+ or depolarization of the postsynaptic membrane during tetanus. Our results indicate that cannabinoid receptor activation does not directly inhibit the molecular mechanisms responsible for long-term synaptic plasticity but instead impairs LTP and LTD by reducing presynaptic neurotransmitter release to a level below that required to depolarize the postsynaptic membrane to relieve Mg2+ blockade of NMDA receptors.

  • cannabinoids
  • cannabinoid receptors
  • hippocampus
  • synaptic transmission
  • long-term potentiation
  • long-term depression
  • learning and memory
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The Journal of Neuroscience: 19 (16)
Journal of Neuroscience
Vol. 19, Issue 16
15 Aug 1999
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Mechanism of Cannabinoid Effects on Long-Term Potentiation and Depression in Hippocampal CA1 Neurons
Dinah L. Misner, Jane M. Sullivan
Journal of Neuroscience 15 August 1999, 19 (16) 6795-6805; DOI: 10.1523/JNEUROSCI.19-16-06795.1999

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Mechanism of Cannabinoid Effects on Long-Term Potentiation and Depression in Hippocampal CA1 Neurons
Dinah L. Misner, Jane M. Sullivan
Journal of Neuroscience 15 August 1999, 19 (16) 6795-6805; DOI: 10.1523/JNEUROSCI.19-16-06795.1999
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Keywords

  • cannabinoids
  • cannabinoid receptors
  • hippocampus
  • synaptic transmission
  • long-term potentiation
  • long-term depression
  • learning and memory

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