RT journal article
T1 Cannabinoid agonists rearrange synaptic vesicles at excitatory synapses and depress motoneuron activity in vivo.
A1 García Morales, Victoria
A1 Montero, F.
A1 Moreno López, Bernardo
A2 BiomedicinaBiotecnología y Salud Pública
K1 Receptor CB1
K1 depresión a corto plazo
K1 neurotransmisión alérgica
AB Impairment of motor skills is one of the most common acute adverse effects of cannabis. Related studieshave focused mainly on psychomotor alterations, and little is known about the direct impact of cannabinoids(CBs) on motoneuron physiology. As key modulators of synaptic function, CBs regulate multipleneuronal functions and behaviors. Presynaptic CB1 mediates synaptic strength depression by inhibitingneurotransmitter release, via a poorly understood mechanism. The present study examined the effect ofCB agonists on excitatory synaptic inputs incoming to hypoglossal motoneurons (HMNs) in vitro andin vivo. The endocannabinoid anandamide (AEA) and the synthetic CB agonist WIN 55,212-2 rapidly andreversibly induced short-term depression (STD) of glutamatergic synapses on motoneurons by a presynapticmechanism. Presynaptic effects were fully reversed by the CB1-selective antagonist AM281.Electrophysiological and electron microscopy analysis showed that WIN 55,212-2 reduced the number ofsynaptic vesicles (SVs) docked to active zones in excitatory boutons. Given that AM281 fully abolisheddepolarization-induced depression of excitation, motoneurons can be feasible sources of CBs, which inturn act as retrograde messengers regulating synaptic function. Finally, microiontophoretic application ofthe CB agonist O-2545 reversibly depressed, presumably via CB1, glutamatergic inspiratory-related activityof HMNs in vivo. Therefore, evidence support that CBs, via presynaptic CB1, induce excitatory STDby reducing the readily releasable pool of SVs at excitatory synapses, then attenuating motoneuronactivity. These outcomes contribute a possible mechanistic basis for cannabis-associated motor performancedisturbances such as ataxia, dysarthria and dyscoordination.
PB Elsevier
SN 0028-3908
YR 2015
FD 2015-01
LK http://hdl.handle.net/10498/30958
UL http://hdl.handle.net/10498/30958
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 21-sep-2026