Editors' ChoiceNeuroscience

Inhaling Your Food

Sci. Signal.  11 Mar 2014:
Vol. 7, Issue 316, pp. ec70
DOI: 10.1126/scisignal.2005247

Cannabinoid consumption increases hunger and the sense of smell (olfaction). The cannabinoid type 1 receptor (CB1) suppresses glutamatergic neurotransmission in mesolimbic brain regions. Using mice lacking CB1 in cortical glutamatergic neurons (Glu-CB1–/– mice), Soria-Gómez et al. investigated the neuronal network that links cannabinoid-induced food craving and olfaction (see also Maldonado-Avilés and DiLeone). Whereas CB1 abundance did not differ between Glu-CB1–/– and wild-type mice in other brain regions, CB1 abundance was lower in the granule cell layer (GCL) of the main olfactory bulb (MOB) in Glu-CB1–/– mice than in that of wild-type mice. Glu-CB1–/– mice ate less food after fasting than wild-type mice. In wild-type mice, fasting increased the amount of the endocannabinoid anandamide in the MOB as well as in the hypothalamus (a mesolimbic region). Infusion of the CB1 antagonist AM251 into the GCL before refeeding decreased food intake in wild-type mice, whereas intra-GCL infusion with the N-methyl-D-aspartate (NMDA) receptor antagonist MK801 increased food intake in both wild-type mice and Glu-CB1–/– mice. In mice lacking expression of CB1 (Stop-CB1 mice, which were created with a loxP-flanked stop cassette), conditional reexpression of CB1 in neurons of the anterior olfactory nucleus (AON) and anterior piriform cortex (APC), which project to the MOB, increased food intake after fasting. Treatment with the plant-derived CB1 agonist THC enhanced fasting-induced food intake (as expected), impaired olfactory habituation, and increased olfactory sensitivity in wild-type mice but not in Glu-CB1–/– mice or those that had an intra-GCL infusion of an allosteric NMDA receptor agonist. Optogenetic techniques in vivo showed that induction of CB1 activity in presynaptic AON/APC neurons reduced glutamatergic excitation of postsynaptic inhibitory granule cells in the MOB. Together, the findings indicate that hunger-induced food intake is mediated by cannabinoid-mediated suppression of glutamatergic neurotransmission from the AON/APC to the MOB in the olfactory circuit.

E. Soria-Gómez, L. Bellocchio, L. Reguero, G. Lepousez, C. Martin, M. Bendahmane, S. Ruehle, F. Remmers, T. Desprez, I. Matias, T. Wiesner, A. Cannich, A. Nissant, A. Wadleigh, H. -C. Pape, A. P. Chiarlone, C. Quarta, D. Verrier, P. Vincent, F. Massa, B. Lutz, M. Guzmán, H. Gurden, G. Ferreira, P. -M. Lledo, P. Grandes, G. Marsicano, The endocannabinoid system controls food intake via olfactory processes. Nat. Neurosci. 17, 407–415 (2014).[PubMed]

J. G. Maldonado-Avilés, R. J. DiLeone, Inhaling: Endocannabinoids and food intake. Nat. Neurosci. 17, 336–337 (2014). [PubMed]