Synaptic plasticity

Activin A, a member of the transforming growth factor β (TGF-β) family, is widely recognized for its neurotrophic and neuroprotective function in the developing and injured brain, respectively. Moreover, in the healthy adult brain, activin A has been shown to tune signal processing at excitatory synapses in a fashion that improves cognitive performance. Because its level in human cerebrospinal fluid rises with age, we wondered whether activin A has a role in mitigating the gradual cognitive decline that healthy individuals experience in late-life...

Brain-derived neurotrophic factor (BDNF), a key neurotrophin within the brain, by selectively activating the TrkB receptor, exerts multimodal effects on neurodevelopment, synaptic plasticity, cellular integrity and neural network dynamics. In parallel, glucocorticoids (GCs), vital steroid hormones, which are secreted by adrenal glands and rapidly diffused across the mammalian body (including the brain), activate two different groups of intracellular receptors, the mineralocorticoid and the glucocorticoid receptors, modulating a wide range of genomic, epigenomic and postgenomic events, also expressed in the neural tissue and implicated in neurodevelopment, synaptic plasticity, cellular homeostasis, cognitive and emotional processing...

AIMS: Ventral pathway circuits are constituted by the interconnected brain areas that are distributed throughout the brain. These brain circuits are primarily involved in processing of object related information in brain. However, their role in object recognition memory (ORM) enhancement remains unknown. Here, we have studied on the implication of these circuits in ORM enhancement and in reversal of ORM deficit in aging. METHODS: The brain areas interconnected to ventral pathway circuits in rat brain were activated by an expression of a protein called regulator of G-protein signaling 14 of 414 amino acids (RGS14414 )...

Alzheimer's disease (AD) is an enigmatic neurological illness that offers few treatment options. Recent exploration has highlighted the crucial connection of the Wnt signaling pathway in AD pathogenesis, shedding light on potential therapeutic targets. The present study focuses on the dual targeting of glycogen synthase kinase-3β (GSK-3β) and casein kinase-1δ (CK-1δ) within the framework of the Wnt signaling pathway as a possible technique for AD intervention. GSK-3β and CK-1δ are multifunctional kinases known for their roles in tau hyperphosphorylation, amyloid processing, and synaptic dysfunction, all of which are major hallmarks of Alzheimer's disease...

Recurrent seizures lead to accumulation of the activity-dependent transcription factor ∆FosB in hippocampal dentate granule cells in both mouse models of epilepsy and mouse models of Alzheimer's disease (AD), which is also associated with increased incidence of seizures. In patients with AD and related mouse models, the degree of ∆FosB accumulation corresponds with increasing severity of cognitive deficits. We previously found that ∆FosB impairs spatial memory in mice by epigenetically regulating expression of target genes such as calbindin that are involved in synaptic plasticity...

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng is a valuable herb in traditional Chinese medicine. Modern research has shown that it has various benefits, including tonifying vital energy, nourishing and strengthening the body, calming the mind, improving cognitive function, regulating fluids, and returning blood pressure, etc. Rg1 is a primary active component of ginseng. It protects hippocampal neurons, improves synaptic plasticity, enhances cognitive function, and boosts immunity. Furthermore, it exhibits anti-aging and anti-fatigue properties and holds great potential for preventing and managing neurodegenerative diseases (NDDs)...

Dynamical balance of excitation and inhibition is usually invoked to explain the irregular low firing activity observed in the cortex. We propose a robust nonlinear balancing mechanism for a random network of spiking neurons, which works also in the absence of strong external currents. Biologically, the mechanism exploits the plasticity of excitatory-excitatory synapses induced by short-term depression. Mathematically, the nonlinear response of the synaptic activity is the key ingredient responsible for the emergence of a stable balanced regime...

Organic memristors as promising electronic units are attracting significant attention owing to their simplicity of molecular structure design. However, fabricating high-quality organic films via novel synthetic technologies and exploring unprecedented chemical structures to achieve excellent memory performance in organic memristor devices are highly challenging. In this work, we report a cathodic electropolymerization to synthesize an ionic azulene-based memristive film (PPMAz-Py+ Br- ) under the molecular-potential and redox coregulation...

BACKGROUND: Accumulation of tau in synapses in the early stages of Alzheimer's disease (AD) has been shown to cause synaptic damage, synaptic loss, and the spread of tau pathology through trans-synaptically connected neurons. Moreover, synaptic loss correlates with a decline in cognitive function, providing an opportunity to investigate therapeutic strategies to target synapses and synaptic tau to rescue or prevent cognitive decline in AD. One of the promising synaptic targets is the 5-HT4 serotonergic receptor present postsynaptically in the brain structures involved in the memory processes...

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) is a widely used therapeutic tool in neurology and psychiatry, but its cellular and molecular mechanisms are not fully understood. Standardizing stimulus parameters, specifically electric field strength, is crucial in experimental and clinical settings. It enables meaningful comparisons across studies and facilitates the translation of findings into clinical practice. However, the impact of biophysical properties inherent to the stimulated neurons and networks on the outcome of rTMS protocols remains not well understood...

N-methyl-D-aspartate (NMDA) receptors, i.e., inotropic glutamate receptors, are important in synaptic plasticity, brain growth, memory, and learning. The activation of NMDA is done by neurotransmitter glutamate and co-agonist (glycine or D-serine) binding. However, the over-activation of NMDA elevates the intracellular calcium influx, which causes various neurological diseases and disorders. Therefore, to prevent excitotoxicity and neuronal death, inhibition of NMDA must be done using its antagonist. This review delineates the structure of subunits of NMDA and the conformational changes induced after the binding of agonists (glycine and D-serine) and antagonists (ifenprodil, etc...

Substantial progress has been made in understanding the genetic architecture of phenotypes involved in a variety of evolutionary processes. Behavioral genetics remains, however, among the least understood. We explore the genetic architecture of spatial cognitive abilities in a wild passerine bird, the mountain chickadee (Poecile gambeli). Mountain chickadees cache thousands of seeds in the fall and require specialized spatial memory to recover these caches throughout the winter. We previously showed that variation in spatial cognition has a direct effect on fitness and has a genetic basis...

The insular cortex, or insula, is a large brain region involved in the detection of thirst and the regulation of water intake. However, our understanding of the topographical, circuit, and molecular mechanisms for controlling water intake within the insula remains parcellated. We found that type-1 cannabinoid (CB1 ) receptors in the insular cortex cells participate in the regulation of water intake and deconstructed the circuit mechanisms of this control. Topographically, we revealed that the activity of excitatory neurons in both the anterior insula (aIC) and posterior insula (pIC) increases in response to water intake, yet only the specific removal of CB1 receptors in the pIC decreases water intake...

From fly to man, the Wingless (Wg)/Wnt signaling molecule is essential for both the stability and plasticity of the nervous system. The Drosophila neuromuscular junction (NMJ) has proven to be a useful system for deciphering the role of Wg in directing activity-dependent synaptic plasticity (ADSP), which, in the motoneuron, has been shown to be dependent on both the canonical and the noncanonical calcium Wg pathways. Here we show that the noncanonical planar cell polarity (PCP) pathway is an essential component of the Wg signaling system controlling plasticity at the motoneuron synapse...

INTRODUCTION: Axonal plasticity is strongly related to neuronal development as well as regeneration. It was recently demonstrated that active mechanical tension, intended as an extrinsic factor, is a valid contribution to the modulation of axonal plasticity. METHODS: In previous publications, our team validated a the "nano-pulling" method used to apply mechanical forces to developing axons of isolated primary neurons using magnetic nanoparticles (MNP) actuated by static magnetic fields...

BACKGROUND AND PURPOSE: Transient hypofunction of the NMDA receptor represents a convergence point for the onset and further development of psychiatric disorders, including schizophrenia. Although the cumulative evidence indicates dysregulation of the hippocampal formation in schizophrenia, the integrity of the synaptic transmission and plasticity conveyed by the somatosensorial inputs to the dentate gyrus, the perforant pathway synapses, have barely been explored in this pathological condition...

Small conductance Ca2+ -activated K+ (SK) channels, expressed throughout the CNS, are comprised of SK1, SK2 and SK3 subunits, assembled as homotetrameric or heterotetrameric proteins. SK channels expressed somatically modulate the excitability of neurons by mediating the medium component of the afterhyperpolarization. Synaptic SK channels shape excitatory postsynaptic potentials and synaptic plasticity. Such SK-mediated effects on neuronal excitability and activity-dependent synaptic strength likely underlie the modulatory influence of SK channels on memory encoding...

Hypertension is a major adverse effect of calcineurin inhibitors, such as tacrolimus (FK506) and cyclosporine, used clinically as immunosuppressants. Calcineurin inhibitor-induced hypertension (CIH) is linked to augmented sympathetic output from the hypothalamic paraventricular nucleus (PVN). GluA2-lacking, Ca2+ -permeable AMPA receptors (CP-AMPARs) are a key feature of glutamatergic synaptic plasticity, yet their role in CIH remains elusive. Here, we found that systemic administration of FK506 in rats significantly increased serine phosphorylation of GluA1 and GluA2 in PVN synaptosomes...

Endoplasmic reticulum-plasma membrane (ER-PM) junctions mediate Ca2+ flux across neuronal membranes. The properties of these membrane contact sites are defined by their lipid content, but little attention has been given to glycosphingolipids (GSLs). Here, we show that GM1-ganglioside, an abundant GSL in neuronal membranes, is integral to ER-PM junctions; it interacts with synaptic proteins/receptors and regulates Ca2+ signaling. In a model of the neurodegenerative lysosomal storage disease, GM1-gangliosidosis, pathogenic accumulation of GM1 at ER-PM junctions due to β-galactosidase deficiency drastically alters neuronal Ca2+ homeostasis...

Dendritic spines, the mushroom-shaped extensions along dendritic shafts of excitatory neurons, are critical for synaptic function and are one of the first neuronal structures disrupted in neurodevelopmental and neurodegenerative diseases. Microtubule (MT) polymerization into dendritic spines is an activity-dependent process capable of affecting spine shape and function. Studies have shown that MT polymerization into spines occurs specifically in spines undergoing plastic changes. However, discerning the function of MT invasion of dendritic spines requires the specific inhibition of MT polymerization into spines, while leaving MT dynamics in the dendritic shaft, synaptically connected axons and associated glial cells intact...