Cannabinoid modulation of hippocampal long-term memory is mediated by mTOR signaling (Nat Neurosci, 2009, 12:1152-1158)

報告日期: 2009/12/18
報告時間: 16:00/16:50
報告學生: 邱全秀
講評老師: 吳豐森

Cannabinoid modulation of hippocampal long-term memory is mediated by mTOR signaling

Emma Puighermanal, Giovanni Marsicano, Arnau Busquets-Garcia, Beat Lutz, Rafael Maldonado & Andrés Ozaita.

Nature neuroscience, 12: 1152-1158, 2009


Speaker: Chiuan-Shiou Chiou (邱全秀)

Commentator: Fong-Sen Wu, Ph. D. (吳豐森老師)

Time: 16:00 ~17:00 Dec. 18, 2009

Place: 602



  CB1 receptor activation induced by cannabis consumption in the hippocampus plays an important role in THC-induced memory impairment. THC-mediated CB1R stimulation transiently triggers the mammalian target of rapamycin (mTOR)/p70S6K pathway. mTOR could regulate the translational rate and the initiation step, also p70S6K could modulate ribosomal protein S6, whose phosphorylation state correlates with translation rates. To address that the involvement of mTOR pathway in the regulation of the protein synthesis machinery could relate to synaptic plasticity and memory impairment, the author demonstrated that acute administration of THC and URB597, a selective inhibitor of the fatty-acid amide hydrolase (FAAH), could produce a measurable deficit in long-term memory which was through transient phosphorylation of Akt/mTOR/p70S6K pathway and dependent on CB1R, as they were absent in CB1R constitutive knockout mice and in mice pretreated with rimonabant (RIM), the CB1R antagonist. Also they confirmed that rapamycin, mTOR inhibitor, and anisomycin, protein synthesis inhibitor, blocked THC-induced protein translation initiation and impaired cognitive responses. To determine the location of the activated subcellular sites in the hippocampus, after pretreating with antagonists for AMPA, mGluR1/5, GABAA or GABAB and NMDA receptors, only NMDA blockade avoided the amnesic-life effects of THC. To understand the specific role of CB1Rs in the different neuronal types in the hippocampus related to the behavioral and biochemical responses to acute THC administration, two lines of CB1R conditional knockout mice were used. They found CB1Rs expressed on GABAergic interneurons through glutamatergic mechanism.



1.     Jessica L. Banko, Francis Poulin, Lingfei Hou, Christine T. DeMaria, Nahum Sonenberg, and Eric Klann. (2005) The translation repressor 4E-BP2 is critical for eIF4F complex formation, synaptic plasticity and memory. J. Neurosci., 25: 9581-9590.

2.     Mauro Costa-Mattioli, Wayne S. Sossin, Eric Klann, and Nahum Sonenberg. (2009) Translational control of long-lasting synaptic plasticity and memory. Neuron, 61: 10-26.