The vestibulo-cerebellum regulates ocular movements and controls head and trunk posture, thus contributing to the correct positioning of the body in space. The cellular network involved is analogous to that of other cerebellar regions, except for the dense presence in the granular layer of unipolar brush cells (UBCs). UBCs are excitatory glutamatergic interneurons endowed with AMPA and NMDA glutamate receptors. It has been shown that each individual UBC receives a single input from one mossy fiber (MF), which forms a giant synapse with the UBC brush-like structure composed of several dendrioles. By using the patch-clamp technique in combination with the rat vestibulo-cerebellum slice preparation, we have investigated the voltage responses of UBCs to MFs excitation. In most UBCs, MFs stimulation evoked an all-or-none response consisting of a burst of action potentials elicited within a short delay (few ms) from the stimulus. Consistent with the literature, this response was blocked by AMPA/NMDA glutamate receptor antagonists APV and NBQX. However, in a significant number of UBCs a different type of postsynaptic response was found, characterized by a very slow membrane depolarization. As a consequence, the time required to reach the voltage threshold for the action potential discharge was considerably long (tens to hundreds of ms). By increasing stimulus intensity to the MFs, the delay of the postsynaptic response decreased, while its duration increased. The delayed response therefore is not an all-or-none phenomenon. Moreover, it was not blocked by APV and NBQX. A basic pharmacological screening revealed that neither metabotropic glutamate, nor GABA or acetylcholine receptors are involved. Additional experiments with ZD 7288 revealed that the slow depolarization depends on Ih, whose level of activation is increased by MFs stimulation. Thus, by setting the slope of the slow depolarization, Ih regulates the time required to fire. The present findings reveal a new modality of synaptic transmission in the vestibulo-cerebellum, characterized by a tunable delay and duration, which may play an important role for vestibular reflexes.
UBCs introduce a tunable delay in vestibolo-cerebellar circuits which depends upon Ih
LOCATELLI, FRANCESCA;MASETTO, SERGIO;D'ANGELO, EGIDIO UGO
2010-01-01
Abstract
The vestibulo-cerebellum regulates ocular movements and controls head and trunk posture, thus contributing to the correct positioning of the body in space. The cellular network involved is analogous to that of other cerebellar regions, except for the dense presence in the granular layer of unipolar brush cells (UBCs). UBCs are excitatory glutamatergic interneurons endowed with AMPA and NMDA glutamate receptors. It has been shown that each individual UBC receives a single input from one mossy fiber (MF), which forms a giant synapse with the UBC brush-like structure composed of several dendrioles. By using the patch-clamp technique in combination with the rat vestibulo-cerebellum slice preparation, we have investigated the voltage responses of UBCs to MFs excitation. In most UBCs, MFs stimulation evoked an all-or-none response consisting of a burst of action potentials elicited within a short delay (few ms) from the stimulus. Consistent with the literature, this response was blocked by AMPA/NMDA glutamate receptor antagonists APV and NBQX. However, in a significant number of UBCs a different type of postsynaptic response was found, characterized by a very slow membrane depolarization. As a consequence, the time required to reach the voltage threshold for the action potential discharge was considerably long (tens to hundreds of ms). By increasing stimulus intensity to the MFs, the delay of the postsynaptic response decreased, while its duration increased. The delayed response therefore is not an all-or-none phenomenon. Moreover, it was not blocked by APV and NBQX. A basic pharmacological screening revealed that neither metabotropic glutamate, nor GABA or acetylcholine receptors are involved. Additional experiments with ZD 7288 revealed that the slow depolarization depends on Ih, whose level of activation is increased by MFs stimulation. Thus, by setting the slope of the slow depolarization, Ih regulates the time required to fire. The present findings reveal a new modality of synaptic transmission in the vestibulo-cerebellum, characterized by a tunable delay and duration, which may play an important role for vestibular reflexes.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.