Biology subjects

Kawaguchi, S.-y.

Publications and source records attributed to Kawaguchi, S.-y..

4 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↗

bioRxiv2023

Asymmetric spread of excitatory synaptic potentialin hippocampal neuronal dendrites revealed by voltage imaging

Processing of synaptic signals in somatodendritic compartments determines the neuronal computation. Although amplification of excitatory signals by local voltage-dependent cation channels has been extensively studied, its spatio-temporal dynamics in elaborate dendritic branches remains obscure because of technical limitation. Using fluorescent voltage imaging throughout dendritic arborizations in hippocampal pyramidal neurons, here we demonstrate a unique Cl--dependent remote computation mechanism equipped in distal branches. Local laser photolysis of caged-glutamate triggered excitatory postsynaptic potentials spreading along dendrites with gradual amplification toward the distal end whereas with attenuation toward the soma. Tour-de-force subcellular patch-clamp recordings from thin branches complemented with biophysical model simulation revealed that the asymmetric augmentation of excitation relies on the TTX-resistant Na+ channels and Cl--conductances accompanied with deeper dendritic resting potential. Taken together, the present study unveils cooperative voltage-dependent actions of cation and anion conductances for dendritic supralinear computation which can locally decode the spatio-temporal context of synaptic inputs.

neuroscience↗

bioRxiv2022

Analogue signaling of somato-dendritic synaptic activity to axon enhances GABA release in young cerebellar molecular layer interneurons

Axons are equipped with the digital signaling capacity by which they generate and faithfully propagate action potentials (APs), and also with the analogue signaling capacity by which subthreshold activity in dendrites and soma is transmitted down the axon. Despite intense work, the extent and physiological role for subthreshold synaptic activity reaching the axonal boutons has remained elusive because of the technical limitation to record from them. To address this issue, we made simultaneous patch-clamp recordings from the axonal varicosities of cerebellar GABAergic interneurons together with their parent soma or postsynaptic target cells in young rat slices and/or primary cultures. Our tour-de-force direct functional dissection indicates that the somatodendritic spontaneous EPSPs are transmitted down the axon for significant distances, depolarizing presynaptic boutons. These analogously transmitted EPSPs augment presynaptic Ca++ influx upon arrival of an immediately following AP through a mechanism that involves a voltage-dependent priming of the Ca++ channels, leading to an increase in GABA release, without any modification in the axonal AP waveform or residual Ca++. Our work highlights the role of the axon in synaptic integration.

neuroscience↗