| First Author | Maroso M | Year | 2016 |
| Journal | Neuron | Volume | 89 |
| Issue | 5 | Pages | 1059-73 |
| PubMed ID | 26898775 | Mgi Jnum | J:240160 |
| Mgi Id | MGI:5882488 | Doi | 10.1016/j.neuron.2016.01.023 |
| Citation | Maroso M, et al. (2016) Cannabinoid Control of Learning and Memory through HCN Channels. Neuron 89(5):1059-73 |
| abstractText | The mechanisms underlying the effects of cannabinoids on cognitive processes are not understood. Here we show that cannabinoid type-1 receptors (CB1Rs) control hippocampal synaptic plasticity and spatial memory through the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels that underlie the h-current (Ih), a key regulator of dendritic excitability. The CB1R-HCN pathway, involving c-Jun-N-terminal kinases (JNKs), nitric oxide synthase, and intracellular cGMP, exerts a tonic enhancement of Ih selectively in pyramidal cells located in the superficial portion of the CA1 pyramidal cell layer, whereas it is absent from deep-layer cells. Activation of the CB1R-HCN pathway impairs dendritic integration of excitatory inputs, long-term potentiation (LTP), and spatial memory formation. Strikingly, pharmacological inhibition of Ih or genetic deletion of HCN1 abolishes CB1R-induced deficits in LTP and memory. These results demonstrate that the CB1R-Ih pathway in the hippocampus is obligatory for the action of cannabinoids on LTP and spatial memory formation. |
