Biology subjects

Inoshita, T.

Publications and source records attributed to Inoshita, T..

2 recordsLinked to original sources

bioRxiv2024

Increased reluctant vesicles underlie synaptic depression by GPR55 in axon terminals of cerebellar Purkinje cells

Control of synaptic transmission efficacy by neuronal activity and neuromodulators is pivotal for brain function. Synaptic suppression by cannabinoids activating CB1 receptors has been extensively studied at the molecular and cellular levels to understand the neuronal basis for effects of cannabis intake. Here, we focused on GPR55, non-canonical type of cannabinoid receptor, which shows sensitivity to cannabidiol included in cannabis, aiming to highlight its actions on presynaptic function. Taking advantage of direct patch-clamp recordings from axon terminals of cerebellar Purkinje cells together with fluorescent imaging of vesicular exocytosis using synapto-pHluorin, we show that GPR55 suppresses synaptic transmission as CB1 receptor does, but through a distinct presynaptic modulation of release machinery. Activation of GPR55 reduced transmitter release by changing neither presynaptic action potential waveform nor Ca2+ influx, but by making a large population of Ca2+-responsive synaptic vesicles insensitive to Ca2+ influx through voltage-gated Ca2+ channels, leading to substantial reduction of the readily releasable pool of vesicles. Thus, the present study identifies a unique mechanism to suppress presynaptic transmitter release by an atypical cannabinoid receptor GPR55, which would enable subtype-specific modulation of neuronal computation by cannabinoid receptors.

neuroscience↗

bioRxiv2023

Timing Control of Purkinje Cell Outputs by Dual cAMP Actions on Axonal Action Potential and Transmitter Release

All-or-none digital signaling based on high-fidelity action potentials (APs) in neuronal axons is pivotal for the temporally precise sending of identical outputs rapidly to widespread multiple target cells. However, technical limitation to directly measure the signaling in small size of intact axonal structures has hindered the evaluation of high-fidelity signal propagation. Here, using direct recordings from axonal trunks and/or terminals of cerebellar Purkinje cells in culture and slice, we demonstrate that the timing of axonal output is delayed by the second messenger cAMP without clear changes of transmission efficacy. Slowed axonal signaling upon cAMP increase was ascribed to negative control of axonal Na+ channels, leading to smaller and hence slower conduction of APs specifically at an axon. On the other hand, a facilitatory effect of cAMP on presynaptic transmitter release, which generally operates at various CNS synapses, was also evident as augmented release probability in Purkinje cell axon terminals, compensating for weakening of release by the reduction of Ca2+ influx upon smaller AP. Taken these results together, our tour-de-force functional dissection of inhibitory axonal signaling unveiled a dynamic control of synaptic output timing by cAMP keeping output strength constant.

neuroscience↗