RT journal article
T1 Endogenous Rho-kinase signaling maintains synaptic strength by stabilizing the size of the readily releasable pool of synaptic vesicles
A1 González Forero, David
A1 Montero, Fernando
A1 García Morales, Victoria
A1 Domínguez, Germán
A1 Gómez Pérez, Laura
A1 García Verdugo, José Manuel
A1 Moreno López, Bernardo
A2 BiomedicinaBiotecnología y Salud Pública
K1 Rho quinasa
K1 motoneurona
AB Rho-associated kinase (ROCK) regulates neural cell migration, proliferation and survival, dendritic spine morphology, and axon guidanceand regeneration. There is, however, little information about whether ROCK modulates the electrical activity and informationprocessing of neuronal circuits. At neonatal stage, ROCK  is expressed in hypoglossal motoneurons (HMNs) and in their afferent inputs,whereasROCK  is found in synaptic terminals on HMNs, but not in their somata. Inhibition of endogenousROCKactivity in neonatal ratbrainstem slices failed to modulate intrinsic excitability of HMNs, but strongly attenuated the strength of their glutamatergic andGABAergic synaptic inputs. The mechanism acts presynaptically to reduce evoked neurotransmitter release. ROCK inhibition increasedmyosin light chain (MLC) phosphorylation, which is known to trigger actomyosin contraction, and reduced the number of synapticvesicles docked to active zones in excitatory boutons. Functional and ultrastructural changes induced by ROCK inhibition were fullyprevented/reverted by MLC kinase (MLCK) inhibition. Furthermore, ROCK inhibition drastically reduced the phosphorylated form ofp21-associated kinase (PAK), which directly inhibits MLCK. We conclude that endogenous ROCK activity is necessary for the normalperformance of motor output commands, because it maintains afferent synaptic strength, by stabilizing the size of the readily releasablepool of synaptic vesicles. The mechanism of action involves a tonic inhibition of MLCK, presumably through PAK phosphorylation. Thismechanism might be present in adults since unilateral microinjection of ROCK or MLCK inhibitors into the hypoglossal nucleus reducedor increased, respectively, whole XIIth nerve activity.
SN 0270-6474
YR 2012
FD 2012-01-04
LK http://hdl.handle.net/10498/30955
UL http://hdl.handle.net/10498/30955
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 21-sep-2026