Neuromodulation via conditional release of endocannabinoids in the spinal locomotor network.
Endocannabinoids act as retrograde signals to modulate synaptic transmission. Little is known, however, about their significance in integrated network activity underlying motor behavior. We have examined the physiological effects of endocannabinoids in a neuronal network underlying locomotor behavior using the isolated lamprey spinal cord. Our results show that endocannabinoids are released during locomotor activity and participate in setting the baseline burst rate. They are released in response to mGluR1 activation and act as retrograde messengers. This conditional release of endocannabinoids can transform motoneurons and crossing interneurons into modulatory neurons by enabling them to regulate their inhibitory synaptic inputs and thus contribute to the modulation of the locomotor burst frequency. These results provide evidence that endocannabinoid retrograde signaling occurs within the locomotor network and contributes to motor pattern generation and regulation in the spinal cord.
Kettunen
Petronella
P
Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
Kyriakatos
Alexandros
A
Hallén
Kristofer
K
El Manira
Abdeljabbar
A
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D002186:Cannabinoids / Q000494:pharmacology; D063388:Endocannabinoids; D007798:Lampreys; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D009415:Nerve Net / Q000187:drug effects / Q000378:metabolism*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D043882:Receptors, Cannabinoid / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D063388:Endocannabinoids; D018377:Neurotransmitter Agents; D043884:Receptor, Cannabinoid, CB1; D043882:Receptors, Cannabinoid; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1