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Lipid Transporter TMEM24/C2CD2L Plays Essential Roles in Retinal Photoreceptor Survival by Regulating Calcium Signaling and Synaptic Transmission.

Retinal neurotransmission is fundamental to vision, relying on the precise calcium-dependent release of glutamate at photoreceptor ribbon synapses. Disruptions in this pathway underlie multiple visual disorders in humans. TMEM24/C2CD2L, an SMP domain-containing phospholipid transporter enriched at endoplasmic reticulum (ER)-plasma membrane (PM) contact sites, regulates phosphoinositide homeostasis and calcium signaling. However, its role in the retina remains unknown. Here, we show that C2CD2L is predominantly expressed in retinal photoreceptors. Using a rod-specific conditional knockout mouse

Enhanced axonal mitochondrial motility and neural activity-induced energy deficits destabilize synaptic transmission in models of bipolar disorder.

Synaptic communication requires mitochondria to supply ATP and buffer calcium at presynaptic terminals. In bipolar disorder, manic episodes are associated with elevated mood and neural activity, but the underlying cellular mechanisms remain unclear. Here we show that hiPSC-derived cortical neurons from donors with bipolar disorder exhibit increased axonal mitochondrial motility and frequent mitochondrial entry-exit transitions, reducing stable mitochondrial retention at presynaptic terminals. This destabilizes local ATP maintenance and calcium buffering, increasing synaptic variability without

Ivabradine reduces neuropathic pain after spinal cord injury by inhibiting excitatory synaptic transmission in the spinal dorsal horn.

Spinal cord injuries (SCIs) can lead to severe neuropathic pain and increased risk of myocardial infarction and heart failure; therefore, th … ts/group; p < 0.01). We concluded that ivabradine reduces SCI-induced pain by inhibiting excitatory synaptic transmission in the spinal dorsal horn.

Обезвоживание, вызванное Cuprizone, вызывает аномальные внутренние свойства и эксцизитационную синапическую трансмиссию в коре головного мозга самца мыши.

Множественный склероз (MS) — демиелионирующее заболевание центральной нервной системы (CNS). Демиэлизация в CNS вызывает гиперальгезию, негативные эмоции и/или когнитивное расстройство. Cuprizone (CPZ), вызванное демиелинацией, является одной из основных моделей обезвоживания грызунов. Передняя кора головного мозга (ACC) — область мозга, которая отвечает за более высокие функции мозга, связанные с симптомами MS. Однако мало что известно о том, приводит ли воздействие CPZ к обезвоживанию в ACC к изменениям присущих нейронам свойств и синаптической передачи. В этом исследовании мы впервые изучил

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). Demyelination in the CNS provokes hyperalgesia, nega … exposure induces demyelination in the ACC coincides with changes to intrinsic neuron properties and synaptic transmission. In this study, we first examined if CPZ exposure induces demyelination in the male mouse ACC. CPZ exposure induced demyelination in the ACC and decreased body weight. In addition, demyelination altered intrinsic properties and excitatory synaptic t …

Interplay between metabotropic glutamate type 4 and adenosine type 1 receptors modulate synaptic transmission in the cerebellar cortex.

The synapses between parallel fibers and Purkinje cells play a pivotal role in cerebellar function. They are intricately governed by a variety of presynaptic receptors, notably by type 4 metabotropic glutamate (mGlu4) receptors and type 1 adenosine (A1) receptors both of which curtail glutamate release upon activation. Despite their pivotal role in regulating synaptic transmission within the cerebellar cortex, functional interactions between mGlu4 and A1 receptors have remained relatively unexplored. To bridge this gap, our study delves into how mGlu4 receptor activity influences A1 receptor-m…

Developmental changes in GABAergic and glycinergic synaptic transmission to rat motoneurons innervating jaw-closing and jaw-opening muscles.

Trigeminal motoneurons (MNs) innervating the jaw-closing and jaw-opening muscles receive numerous inhibitory synaptic inputs from GABAergic and glycinergic neurons, which are essential for oromotor functions, such as the orofacial reflex, suckling, and mastication. The properties of the GABAergic and glycinergic inputs of these MNs undergo developmental alterations during the period in which their feeding behavior proceeds from suckling to mastication; however, the detailed characteristics of the developmental patterns of GABAergic and glycinergic transmission in these neurons remain to be elu

Cortical Seizures in FoxG1+/- Mice are Accompanied by Akt/S6 Overactivation, Excitation/Inhibition Imbalance and Impaired Synaptic Transmission.

The correct morphofunctional shaping of the cerebral cortex requires a continuous interaction between intrinsic (genes/molecules expressed within the tissue) and extrinsic (e.g., neural activity) factors at all developmental stages. Forkhead Box G1 (FOXG1) is an evolutionarily conserved transcription factor, essential for the cerebral cortex patterning and layering. FOXG1-related disorders, including the congenital form of Rett syndrome, can be caused by deletions, intragenic mutations or duplications. These genetic alterations are associated with a complex phenotypic spectrum, spanning from i

The role of gamma-aminobutyric acid/glycinergic synaptic transmission in mediating bilirubin-induced hyperexcitation in developing auditory neurons.

Hyperbilirubinemia is a common clinical phenomenon observed in human newborns. A high level of bilirubin can result in severe jaundice and bilirubin encephalopathy. However, the cellular mechanisms underlying bilirubin excitotoxicity are unclear. Our previous studies showed the action of gamma-aminobutyric acid (GABA)/glycine switches from excitatory to inhibitory during development in the ventral cochlear nucleus (VCN), one of the most sensitive auditory nuclei to bilirubin toxicity. In the present study, we investigated the roles of GABAA/glycine receptors in the induction of bilirubin hyper

Dynamic effects of TNF-α on synaptic transmission in mice over time following sciatic nerve chronic constriction injury.

Nerve injury-induced central sensitization can manifest as an increase in excitatory synaptic transmission and/or as a decrease in inhibitory synaptic transmission in spinal dorsal horn neurons. Cytokines such as tumor necrosis factor-α (TNF-α) are induced in the spinal cord under various injury conditions and contribute to neuropathic pain. In this study we examined the effect of TNF-α in modulating excitatory and inhibitory synaptic input to spinal substantia gelatinosa (SG) neurons over time in mice following chronic constriction injury (CCI) of the sciatic nerve. Whole cell patch-clamp stu…

Impact of the leaner P/Q-type Ca2+ channel mutation on excitatory synaptic transmission in cerebellar Purkinje cells.

Loss-of-function mutations in the gene encoding P/Q-type Ca(2+) channels cause cerebellar ataxia in mice and humans, but the underlying mechanism(s) are unknown. These Ca(2+) channels play important roles in regulating both synaptic transmission and intrinsic membrane properties, and defects in either could contribute to ataxia. Our previous work described changes in intrinsic properties and excitability of cerebellar Purkinje cells (PCs) resulting from the leaner mutation, which is known to reduce whole-cell Ca(2+) currents in PCs and cause severe ataxia. Here we describe the impact of this m…

Activation of adenosine A1 and A2 receptors differentially modulates calcium channels and glycinergic synaptic transmission in rat brainstem.

Multiple types of calcium channels are responsible for calcium influx that triggers transmitter release in the mammalian CNS. To test the co … mega-agatoxin IVA-sensitive) channels. At the presynaptic terminal, N- and P-type channels mediated synaptic transmission. omega-CgTx occluded synaptic inhibition by A1 receptor activation, suggesting that synaptic inhibition was mediated predominantly by N-type channel inhibition. A2 receptor activation facilitated synaptic transmission, probably through potentiation …

Treatment with perampanel alleviates depression-like behavior in mice via modulating GluN2B expression to improve excitatory synaptic transmission.

Antidepressants that target the glutamatergic system, such as ketamine, have shown promising results. However, the contribution of other pot … ion of the AMPA receptor subunit GluA1 (Gria1), and improve the functional impairment of excitatory synaptic transmission in the mPFC in depression susceptible mice. Meanwhile, Naïve mice (non-stressed controls) administered perampanel would rapidly exhibit depression-like behaviors. This is because perampanel inhibits the function of excitatory synaptic transmission i …

The glioma metabolite, D-2-hydroxyglutarate (D-2-HG), reduces synaptic transmission and epileptiform bursts in neocortical slices.

80% of patients with low-grade gliomas containing mutations of the metabolic enzyme isocitrate dehydrogenase (IDH) experience seizures, of w … e to D-2-HG inhibits seizure-like activity in neocortical slices possibly by suppressing excitatory synaptic transmission. Thus, these data do not support the initial hypothesis that D-2-HG may excite neurons and promote seizures by mimicking glutamate actions.

Oleanolic acid-3-glucoside, a synthetic oleanane-type saponin, ameliorates methylmercury-induced dysfunction of synaptic transmission in mice.

Methylmercury (MeHg) is widely distributed in nature and is known to cause neurotoxic effects. This study aimed to examine the anti-MeHg activity of oleanolic acid-3-glucoside (OA3Glu), a synthetic oleanane-type saponin derivative, by evaluating its effects on motor function, pathology, and electrophysiological properties in a mouse model of MeHg poisoning. Mice were orally administered 2 or 4 mg·kg-1·d-1 MeHg with or without 100 µg·kg-1·d-1 OA3Glu 5x/week for four weeks. Motor function was evaluated using beam-walking and dynamic weight-bearing (DWB) tests. High-dose MeHg exposure significant

Mechanisms of delta opioid receptor inhibition of parallel fibers-purkinje cell synaptic transmission in the mouse cerebellar cortex.

Delta opioid receptors (DORs) are widely expressed throughout the central nervous system, including the cerebellum, where they play a regulatory role in neurogenesis. In the cerebellar cortex, Purkinje cells (PCs), the sole output neurons, receive glutamatergic synaptic input from parallel fibers (PFs)-the axonal extensions of granule cells-forming PF-PC synapses. However, the precise distribution of DORs within these synapses and their impact on synaptic transmission remain unclear. In this study, we utilized whole-cell patch-clamp recordings and neuropharmacological approaches to explore the…

Autism spectrum disorder-like behavior caused by reduced excitatory synaptic transmission in pyramidal neurons of mouse prefrontal cortex.

Autism spectrum disorder (ASD) is thought to result from deviation from normal development of neural circuits and synaptic function. Many genes with mutation in ASD patients have been identified. Here we report that two molecules associated with ASD susceptibility, contactin associated protein-like 2 (CNTNAP2) and Abelson helper integration site-1 (AHI1), are required for synaptic function and ASD-related behavior in mice. Knockdown of CNTNAP2 or AHI1 in layer 2/3 pyramidal neurons of the developing mouse prefrontal cortex (PFC) reduced excitatory synaptic transmission, impaired social interac…

Mutation of the Dyslexia-Associated Gene Dcdc2 Enhances Glutamatergic Synaptic Transmission Between Layer 4 Neurons in Mouse Neocortex.

Variants in DCDC2 have been associated with reading disability in humans, and targeted mutation of Dcdc2 in mice causes impairments in both learning and sensory processing. In this study, we sought to determine whether Dcdc2 mutation affects functional synaptic circuitry in neocortex. We found mutation in Dcdc2 resulted in elevated spontaneous and evoked glutamate release from neurons in somatosensory cortex. The probability of release was decreased to wild-type level by acute application of N-methyl-d-aspartate receptor (NMDAR) antagonists when postsynaptic NMDARs were blocked by intracellula

N-type voltage gated calcium channels mediate excitatory synaptic transmission in the anterior cingulate cortex of adult mice.

Voltage gated calcium channels (VGCCs) are well known for its importance in synaptic transmission in the peripheral and central nervous system. However, the role of different VGCCs in the anterior cingulate cortex (ACC) has not been studied. Here, we use a multi-electrode array recording system (MED64) to study the contribution of different types of calcium channels in glutamatergic excitatory synaptic transmission in the ACC. We found that only the N-type calcium channel blocker ω-conotoxin-GVIA (ω-Ctx-GVIA) produced a great inhibition of basal synaptic transmission, especially in the superfi…

Impaired neural transmission and synaptic plasticity in superior cervical ganglia from β-amyloid rat model of Alzheimer's disease.

Basal synaptic transmission and activity-dependent synaptic plasticity were evaluated in superior cervical sympathetic ganglia (SCG) of amyloid-β rat model of Alzheimer's disease (Aβ rat) using electrophysiological and molecular techniques. Rats were administered Aβ peptides (a mixture of 1:1 Aβ1-40 and Aβ1-42) by chronic intracerebroventricular infusion via 14-day mini-osmotic pumps (300 pmol/day). Control rats received Aβ40-1 (inactive reverse peptide: 300 pmol/day). Ganglionic compound action potentials were recorded before (basal) and after repetitive stimulation. In isolated SCG, ganglion…