Nihon Yakurigaku Zasshi
March 2023
Dendrites receive excitatory synaptic inputs from upstream cell ensembles to trigger action potentials at the cell body. The efficiency of excitatory synaptic inputs on neuronal output depends on the spatiotemporal pattern of synaptic inputs. However, technical limitations still make it unclear how synaptic inputs are organized along dendrites in both space and time.
View Article and Find Full Text PDFCerebral edema is a major contributor to the mortality associated with ischemic stroke and traumatic brain injuries; however, limited therapeutic strategies are available for cerebral edema. Aquaporin-4 (AQP4), the main water channel in the brain plays a key role in water homeostasis and edema formation in the central nervous system. Therefore, regulation of AQP4 function or expression is considered a possible target for treatment of edema.
View Article and Find Full Text PDFMost excitatory inputs arrive at dendritic spines in a postsynaptic neuron. To understand dendritic information processing, it is critical to scrutinize the spatiotemporal dynamics of synaptic inputs along dendrites. This protocol combines spinning-disk confocal imaging with whole-cell patch-clamp recording to perform wide-field, high-speed optical recording of synaptic inputs in a neuron loaded with a calcium indicator in cultured networks.
View Article and Find Full Text PDFTwo-photon imaging is a major recording technique used in neuroscience. However, it suffers from several limitations, including a low sampling rate, the nonlinearity of calcium responses, the slow dynamics of calcium dyes and a low SNR, all of which severely limit the potential of two-photon imaging to elucidate neuronal dynamics with high temporal resolution. We developed a hyperacuity algorithm (HA_time) based on an approach that combines a generative model and machine learning to improve spike detection and the precision of spike time inference.
View Article and Find Full Text PDFCa2+ is one of the most important second messengers in cells. A far-red to near-infrared (NIR) Ca2+ fluorescent probe is useful for multi-color imaging in GFP or YFP-expressing biosamples. Here we developed a cytosolically localized far-red to NIR rhodamine-based fluorescent probe for Ca2+, CaSiR-2 AM, while rhodamine dyes are basically localized to mitochondria or lysosomes in cells.
View Article and Find Full Text PDFThe sequential reactivation of memory-relevant neuronal ensembles during hippocampal sharp-wave (SW) ripple oscillations reflects cognitive processing. However, how a downstream neuron decodes this spatiotemporally organized activity remains unexplored. Using subcellular calcium imaging from CA1 pyramidal neurons in ex vivo hippocampal networks, we discovered that neighboring spines are activated serially along dendrites toward or away from cell bodies.
View Article and Find Full Text PDFBackground: A method that promotes the retrieval of lost long-term memories has not been well established. Histamine in the central nervous system is implicated in learning and memory, and treatment with antihistamines impairs learning and memory. Because histamine H receptor inverse agonists upregulate histamine release, the inverse agonists may enhance learning and memory.
View Article and Find Full Text PDFThe effect of excitatory synaptic input on the excitation of the cell body is believed to vary depending on where and when the synaptic activation occurs in dendritic trees and the spatiotemporal modulation by inhibitory synaptic input. However, few studies have examined how individual synaptic inputs influence the excitability of the cell body in spontaneously active neuronal networks mainly because of the lack of an appropriate method. We developed a calcium imaging technique that monitors synaptic inputs to hundreds of spines from a single neuron with millisecond resolution in combination with whole-cell patch-clamp recordings of somatic excitation.
View Article and Find Full Text PDFThe specific effects of sleep on synaptic plasticity remain unclear. We report that mouse hippocampal sharp-wave ripple oscillations serve as intrinsic events that trigger long-lasting synaptic depression. Silencing of sharp-wave ripples during slow-wave states prevented the spontaneous down-regulation of net synaptic weights and impaired the learning of new memories.
View Article and Find Full Text PDFFunctional multineuron calcium imaging (fMCI) provides a useful experimental platform to simultaneously capture the spatiotemporal patterns of neuronal activity from a large cell population in situ. However, fMCI often suffers from low signal-to-noise ratios (S/N). The main factor that causes the low S/N is shot noise that arises from photon detectors.
View Article and Find Full Text PDFThe dynamic interactions between synaptic excitation and inhibition (E/I) shape membrane potential fluctuations and determine patterns of neuronal outputs; however, the spatiotemporal organization of these interactions within a single cell is poorly understood. Here, we investigated the relationship between local synaptic excitation and global inhibition in hippocampal pyramidal neurons using functional dendrite imaging in combination with whole-cell recordings of inhibitory postsynaptic currents. We found that the sums of spine inputs over dendritic trees were counterbalanced by a proportional amount of somatic inhibitory inputs.
View Article and Find Full Text PDFBackground: Calcium imaging has become a fundamental modality for studying neuronal circuit dynamics both in vitro and in vivo. However, identifying calcium events (CEs) from spectral data remains laborious and difficult, especially since the signal-to-noise ratio (SNR) often falls below 2. Existing automated signal detection methods are generally applied at high SNRs, leaving a large need for an automated algorithm that can accurately extract CEs from fluorescence intensity data of SNR 2 and below.
View Article and Find Full Text PDFActivity patterns of neural population are constrained by underlying biological mechanisms. These patterns are characterized not only by individual activity rates and pairwise correlations but also by statistical dependencies among groups of neurons larger than two, known as higher-order interactions (HOIs). While HOIs are ubiquitous in neural activity, primary characteristics of HOIs remain unknown.
View Article and Find Full Text PDFCrosstalk between neurons and glia may constitute a significant part of information processing in the brain. We present a novel method of statistically identifying interactions in a neuron-glia network. We attempted to identify neuron-glia interactions from neuronal and glial activities via maximum-a-posteriori (MAP)-based parameter estimation by developing a generalized linear model (GLM) of a neuron-glia network.
View Article and Find Full Text PDFSpontaneous neuronal activity is present in virtually all brain regions, but neither its function nor spatiotemporal patterns are fully understood. Ex vivo organotypic slice cultures may offer an opportunity to investigate some aspects of spontaneous activity, because they self-restore their networks that collapsed during slicing procedures. In hippocampal networks, we compared the levels and patterns of in vivo spontaneous activity to those in acute and cultured slices.
View Article and Find Full Text PDFHippocampal sharp wave (SW)/ripple complexes are thought to contribute to memory consolidation. Previous studies suggest that behavioral rewards facilitate SW occurrence in vivo. However, little is known about the precise mechanism underlying this enhancement.
View Article and Find Full Text PDFAstrocytes are thought to detect neuronal activity in the form of intracellular calcium elevations; thereby, astrocytes can regulate neuronal excitability and synaptic transmission. Little is known, however, about how the astrocyte calcium signal regulates the activity of neuronal populations. In this study, we addressed this issue using functional multineuron calcium imaging in hippocampal slice cultures.
View Article and Find Full Text PDFCortical microcircuits are nonrandomly wired by neurons. As a natural consequence, spikes emitted by microcircuits are also nonrandomly patterned in time and space. One of the prominent spike organizations is a repetition of fixed patterns of spike series across multiple neurons.
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