Understanding OLM interneurons: Characterization, circuitry, and significance in memory and navigation.

Understanding the intricate mechanisms underlying memory formation and retention relies on unraveling how the hippocampus, a structure fundamental for memory acquisition, is organized. Within the complex hippocampal network, interneurons play a crucial role in orchestrating memory processes. Among these interneurons, Oriens-Lacunosum Moleculare (OLM) cells emerge as key regulators, governing the flow of information to CA1 pyramidal cells.

Kainate receptors regulate synaptic integrity and plasticity by forming a complex with synaptic organizers in the cerebellum.

Kainate (KA)-type glutamate receptors (KARs) are implicated in various neuropsychiatric and neurological disorders through their ionotropic and metabotropic actions. However, compared to AMPA- and NMDA-type receptor functions, many aspects of KAR biology remain incompletely understood. Our study demonstrates an important role of KARs in organizing climbing fiber (CF)-Purkinje cell (PC) synapses and synaptic plasticity in the cerebellum, independently of their ion channel or metabotropic functions.

Adenosine A receptors control synaptic remodeling in the adult brain.

The molecular mechanisms underlying circuit re-wiring in the mature brain remains ill-defined. An eloquent example of adult circuit remodelling is the hippocampal mossy fiber (MF) sprouting found in diseases such as temporal lobe epilepsy. The molecular determinants underlying this retrograde re-wiring remain unclear.

Losing balance: Kainate receptors and psychiatric disorders comorbidities.

Cognition and behavior are tightly linked to synaptic function. A growing body of evidence suggests that aberrant neurotransmission, caused by changes in synaptic protein expression levels, may be a major cause underlying different brain disorders. These changes in expression result in abnormal synaptic organization or function, leading to impaired neurotransmission and unbalanced circuit operations.

Diffusion-weighted MRI in neurodegenerative and psychiatric animal models: Experimental strategies and main outcomes.

Preclinical MRI approaches constitute a key tool to study a wide variety of neurological and psychiatric illnesses, allowing a more direct investigation of the disorder substrate and, at the same time, the possibility of back-translating such findings to human subjects. However, the lack of consensus on the optimal experimental scheme used to acquire the data has led to relatively high heterogeneity in the choice of protocols, which can potentially impact the comparison between results obtained by different groups, even using the same animal model. This is especially true for diffusion-weighted MRI data, where certain experimental choices can impact not only on the accuracy and precision of the extracted biomarkers, but also on their biological meaning.

Kainate Receptors, Homeostatic Gatekeepers of Synaptic Plasticity.

Extensive research over the past decades has characterized multiple forms of synaptic plasticity, identifying them as key processes that allow the brain to operate in a dynamic manner. Within the wide variety of synaptic plasticity modulators, kainate receptors are receiving increasing attention, given their diversity of signaling mechanisms and cellular expression profile. Here, we summarize the experimental evidence about the involvement of kainate receptor signaling in the regulation of short- and long-term plasticity, from the perspective of the regulation of neurotransmitter release.

Unbalanced dendritic inhibition of CA1 neurons drives spatial-memory deficits in the Ts2Cje Down syndrome model.

Overinhibition is assumed one of the main causes of cognitive deficits (e.g. memory impairment) in mouse models of Down syndrome (DS).

-(7-(1-Imidazol-1-yl)-2,3-dioxo-6-(trifluoromethyl)-3,4-dihydroquinoxalin-1(2)-yl)benzamide, a New Kainate Receptor Selective Antagonist and Analgesic: Synthesis, X-ray Crystallography, Structure-Affinity Relationships, and in Vitro and in Vivo Pharmacology.

Selective pharmacological tool compounds are invaluable for understanding the functions of the various ionotropic glutamate receptor subtypes. For the kainate receptors, these compounds are few. Here we have synthesized nine novel quinoxaline-2,3-diones with substitutions in the 7-position to investigate the structure-activity relationship at kainate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors.

Increased Grik4 Gene Dosage Causes Imbalanced Circuit Output and Human Disease-Related Behaviors.

Altered glutamatergic neurotransmission is thought to contribute to mental disorders and neurodegenerative diseases. Copy-number variation in genes associated with glutamatergic synapses represents a source of genetic variability, possibly underlying neurological and mental disease susceptibility. The GRIK4 gene encodes a high-affinity kainate receptor subunit of essentially unknown function, although de novo duplication of the 11q23.

Glutamate-induced and NMDA receptor-mediated neurodegeneration entails P2Y1 receptor activation.

Despite the characteristic etiologies and phenotypes, different brain disorders rely on common pathogenic events. Glutamate-induced neurotoxicity is a pathogenic event shared by different brain disorders. Another event occurring in different brain pathological conditions is the increase of the extracellular ATP levels, which is now recognized as a danger and harmful signal in the brain, as heralded by the ability of P2 receptors (P2Rs) to affect a wide range of brain disorders.

Antimicrobial peptide-gold nanoscale therapeutic formulation with high skin regenerative potential.

Chronic skin wounds affect ≈3% of persons aged >60years (Davies et al., 2007) [1]. These wounds are typically difficult to heal by conventional therapies and in many cases they get infected making even harder the regeneration process.

Non-canonical Signaling, the Hidden Life of Ligand-Gated Ion Channels.

Neurotransmitter receptors are responsible for the transfer of information across the synapse. While ionotropic receptors form ion channels and mediate rapid membrane depolarization, so-called metabotropic receptors exert their action though slower, less direct intracellular signaling pathways. Glutamate, GABA, and acetylcholine can activate both ionotropic and metabotropic receptors, yet the distinction between these "canonical" signaling systems has become less clear since ionotropic receptors were proposed to also activate second messenger systems, defining a "non-canonical" signaling pathway.

Optical control of endogenous receptors and cellular excitability using targeted covalent photoswitches.

Light-regulated drugs allow remotely photoswitching biological activity and enable plausible therapies based on small molecules. However, only freely diffusible photochromic ligands have been shown to work directly in endogenous receptors and methods for covalent attachment depend on genetic manipulation. Here we introduce a chemical strategy to covalently conjugate and photoswitch the activity of endogenous proteins and demonstrate its application to the kainate receptor channel GluK1.

Coccydynia related to the use of a contraceptive vaginal ring.

Coccydynia is a syndrome that rheumatologists encounter frequently in the form of tailbone pain, which is usually worse when sitting. Although the most common origin is trauma, there are several other possible causes of pain in the coccyx. We present an unusual case in which coccydynia developed shortly after the insertion of a contraceptive vaginal ring and remitted completely upon removal of this system.

Increased Dosage of High-Affinity Kainate Receptor Gene grik4 Alters Synaptic Transmission and Reproduces Autism Spectrum Disorders Features.

Unlabelled: The understanding of brain diseases requires the identification of the molecular, synaptic, and cellular disruptions underpinning the behavioral features that define the disease. The importance of genes related to synaptic function in brain disease has been implied in studies describing de novo germline mutations and copy number variants. Indeed, de novo copy number variations (deletion or duplication of a chromosomal region) of synaptic genes have been recently implicated as risk factors for mental retardation or autism.

A proteomic analysis reveals the interaction of GluK1 ionotropic kainate receptor subunits with Go proteins.

Kainate receptors (KARs) are found ubiquitously in the CNS and are present presynaptically and postsynaptically regulating synaptic transmission and excitability. Functional studies have proven that KARs act as ion channels as well as potentially activating G-proteins, thus indicating the existance of a dual signaling system for KARs. Nevertheless, it is not clear how these ion channels activate G-proteins and which of the KAR subunits is involved.

Synaptic Targeting of Kainate Receptors.

When native and recombinant kainate receptors (KARs) are compared, there is a mismatch in several of their functional properties. While both generate currents, synaptic responses mediated by KARs have rarely observed in cultured hippocampal neurons. The recent discovery of auxiliary proteins for KARs, such as Netos, offers an explanation for these discrepancies.

Epilog: Cajal's unique and legitimated school.

Santiago Ramón y Cajal is recognized as the founder of modern neuroscience, his discoveries representing the fundamental pillars of our current understanding of the nervous system. As Cajal's career spanned a critical period in Spanish history, he witnessed strong social demands for progress in culture, education, and science. Indeed, the life of Santiago Ramón y Cajal can be considered to reflect the gradual development of Spanish science from the last third of the 19th century.

CRMP2 tethers kainate receptor activity to cytoskeleton dynamics during neuronal maturation.

The CRMP2 and CRMP4 proteins are strongly expressed in the developing nervous system, mediating neurite outgrowth, neuronal polarity, and axon guidance. In the present study, we demonstrate the interaction of the CRMP2 and CRMP4 proteins with the GluK5 subunit of the kainate (KA) receptor (KAR) and investigated the role of KARs in modulating the development of cultured mouse DRG neurons. We found that KARs modulate neuronal maturation and neurite outgrowth in a bidirectional manner.

Kainate receptors in health and disease.

Our understanding of the molecular properties of kainate receptors and their involvement in synaptic physiology has progressed significantly over the last 30 years. A plethora of studies indicate that kainate receptors are important mediators of the pre- and postsynaptic actions of glutamate, although the mechanisms underlying such effects are still often a topic for discussion. Three clear fields related to their behavior have emerged: there are a number of interacting proteins that pace the properties of kainate receptors; their activity is unconventional since they can also signal through G proteins, behaving like metabotropic receptors; they seem to be linked to some devastating brain diseases.

Amelioration of ischemic brain damage by peritoneal dialysis.

Ischemic stroke is a devastating condition, for which there is still no effective therapy. Acute ischemic stroke is associated with high concentrations of glutamate in the blood and interstitial brain fluid. The inability of the tissue to retain glutamate within the cells of the brain ultimately provokes neuronal death.

Spontaneous activity regulates Robo1 transcription to mediate a switch in thalamocortical axon growth.

Developing axons must control their growth rate to follow the appropriate pathways and establish specific connections. However, the regulatory mechanisms involved remain elusive. By combining live imaging with transplantation studies in mice, we found that spontaneous calcium activity in the thalamocortical system and the growth rate of thalamocortical axons were developmentally and intrinsically regulated.