| First Author | Sugaya Y | Year | 2013 |
| Journal | J Neurosci | Volume | 33 |
| Issue | 8 | Pages | 3588-601 |
| PubMed ID | 23426686 | Mgi Jnum | J:195134 |
| Mgi Id | MGI:5476572 | Doi | 10.1523/JNEUROSCI.3141-12.2013 |
| Citation | Sugaya Y, et al. (2013) The endocannabinoid 2-arachidonoylglycerol negatively regulates habituation by suppressing excitatory recurrent network activity and reducing long-term potentiation in the dentate gyrus. J Neurosci 33(8):3588-601 |
| abstractText | Endocannabinoids are known to mediate retrograde suppression of synaptic transmission, modulate synaptic plasticity, and influence learning and memory. The 2-arachidonoylglycerol (2-AG) produced by diacylglycerol lipase alpha (DGLalpha) is regarded as the major endocannabinoid that causes retrograde synaptic suppression. To determine how 2-AG signaling influences learning and memory, we subjected DGLalpha knock-out mice to two learning tasks. We tested the mice using habituation and odor-guided transverse patterning tasks that are known to involve the dentate gyrus and the CA1, respectively, of the hippocampus. We found that DGLalpha knock-out mice showed significantly faster habituation to an odor and a new environment than wild-type littermates with normal performance in the transverse patterning task. In freely moving animals, long-term potentiation (LTP) induced by theta burst stimulation was significantly larger at perforant path-granule cell synapses in the dentate gyrus of DGLalpha knock-out mice. Importantly, prior induction of synaptic potentiation at this synapse caused a significant retardation of habituation in DGLalpha knock-out but not in wild-type littermates. The excitability of granule cells became higher in DGLalpha knock-out mice after they generated action potentials. Since no differences were found in intrinsic membrane properties and responses to odor stimuli in granule cells, the elevated excitability is considered to result from enhanced activity of an excitatory recurrent network composed of granule cells and mossy cells. These results suggest that retrograde 2-AG signaling negatively regulates habituation by suppressing excitatory recurrent network activity and reducing LTP in the dentate gyrus. |
