Astrocytes mediate two forms of spike timing-dependent depression at entorhinal cortex-hippocampal synapses.

The entorhinal cortex (EC) connects to the hippocampus sending different information from cortical areas that is first processed at the dentate gyrus (DG) including spatial, limbic and sensory information. Excitatory afferents from lateral (LPP) and medial (MPP) perforant pathways of the EC connecting to granule cells of the DG play a role in memory encoding and information processing and are deeply affected in humans suffering Alzheimer's disease and temporal lobe epilepsy, contributing to the dysfunctions found in these pathologies. The plasticity of these synapses is not well known yet, as are not known the forms of long-term depression (LTD) existing at those connections.

Developmental Spike Timing-Dependent Long-Term Depression Requires Astrocyte d-Serine at L2/3-L2/3 Synapses of the Mouse Somatosensory Cortex.

Spike timing-dependent plasticity (STDP) is a learning rule important for synaptic refinement and for learning and memory during development. While different forms of presynaptic t-LTD have been deeply investigated, little is known about the mechanisms of somatosensory cortex postsynaptic t-LTD. In the present work, we investigated the requirements and mechanisms for induction of developmental spike timing-dependent long-term depression (t-LTD) at L2/3-L2/3 synapses in the juvenile mouse somatosensory cortex.

Adenosine and Cortical Plasticity.

Brain plasticity is the ability of the nervous system to change its structure and functioning in response to experiences. These changes occur mainly at synaptic connections, and this plasticity is named . During postnatal development, environmental influences trigger changes in synaptic plasticity that will play a crucial role in the formation and refinement of brain circuits and their functions in adulthood.

Cajal, the neuronal theory and the idea of brain plasticity.

This paper reviews the importance of Cajal's neuronal theory (the Neuron Doctrine) and the origin and importance of the idea of brain plasticity that emerges from this theory. We first comment on the main Cajal's discoveries that gave rise and confirmed his Neuron Doctrine: the improvement of staining techniques, his approach to morphological laws, the concepts of dynamic polarisation, neurogenesis and neurotrophic theory, his first discoveries of the nerve cell as an independent cell, his research on degeneration and regeneration and his fight against reticularism. Second, we review Cajal's ideas on brain plasticity and the years in which they were published, to finally focus on the debate on the origin of the term plasticity and its conceptual meaning, and the originality of Cajal's proposal compared to those of other authors of the time.

A Neuroligin-1 mutation associated with Alzheimer's disease produces memory and age-dependent impairments in hippocampal plasticity.

Alzheimer's disease (AD) is characterized by memory impairments and age-dependent synapse loss. Experimental and clinical studies have shown decreased expression of the glutamatergic protein Neuroligin-1 (Nlgn1) in AD. However, the consequences of a sustained reduction of Nlgn1 are unknown.

Neuronal and astrocyte determinants of critical periods of plasticity.

Windows of plasticity allow environmental experiences to produce intense activity-dependent changes during postnatal development. The reordering and refinement of neural connections occurs during these periods, significantly influencing the formation of brain circuits and physiological processes in adults. Recent advances have shed light on factors that determine the onset and duration of sensitive and critical periods of plasticity.

ARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain.

Molecular diversity of microglia, the resident immune cells in the CNS, is reported. Whether microglial subsets characterized by the expression of specific proteins constitute subtypes with distinct functions has not been fully elucidated. Here we describe a microglial subtype expressing the enzyme arginase-1 (ARG1; that is, ARG1 microglia) that is found predominantly in the basal forebrain and ventral striatum during early postnatal mouse development.

Timing to be precise? An overview of spike timing-dependent plasticity, brain rhythmicity, and glial cells interplay within neuronal circuits.

In the mammalian brain information processing and storage rely on the complex coding and decoding events performed by neuronal networks. These actions are based on the computational ability of neurons and their functional engagement in neuronal assemblies where precise timing of action potential firing is crucial. Neuronal circuits manage a myriad of spatially and temporally overlapping inputs to compute specific outputs that are proposed to underly memory traces formation, sensory perception, and cognitive behaviors.

Targeting galectin-3 to counteract spike-phase uncoupling of fast-spiking interneurons to gamma oscillations in Alzheimer's disease.

Background: Alzheimer's disease (AD) is a progressive multifaceted neurodegenerative disorder for which no disease-modifying treatment exists. Neuroinflammation is central to the pathology progression, with evidence suggesting that microglia-released galectin-3 (gal3) plays a pivotal role by amplifying neuroinflammation in AD. However, the possible involvement of gal3 in the disruption of neuronal network oscillations typical of AD remains unknown.

Adenosine and Astrocytes Control Critical Periods of Neural Plasticity.

Windows of plasticity are fundamental for the correct formation of definitive brain circuits; these periods drive sensory and motor learning during development and ultimately learning and memory in adults. However, establishing windows of plasticity also imposes limitations on the central nervous system in terms of its capacity to recover from injury. Recent evidence highlights the important role that astrocytes and adenosine seem to play in controlling the duration of these critical periods of plasticity.

Role of Group I Metabotropic Glutamate Receptors in Spike Timing-Dependent Plasticity.

Metabotropic glutamate receptors (mGluRs) are G-protein-coupled receptors that exhibit enormous diversity in their expression patterns, sequence homology, pharmacology, biophysical properties and signaling pathways in the brain. In general, mGluRs modulate different traits of neuronal physiology, including excitability and plasticity processes. Particularly, group I mGluRs located at the pre- or postsynaptic compartments are involved in spike timing-dependent plasticity (STDP) at hippocampal and neocortical synapses.

Modeling Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes Syndrome Using Patient-Derived Induced Neurons Generated by Direct Reprogramming.

Mitochondrial diseases are a heterogeneous group of rare genetic disorders caused by mutations in nuclear or mitochondrial DNA (mtDNA). These diseases are frequently multisystemic, although mainly affect tissues that require large amounts of energy such as the brain. Mutations in mitochondrial transfer RNA (mt-tRNA) lead to defects in protein translation that may compromise some or all mtDNA-encoded proteins.

Adenosine and Astrocytes Determine the Developmental Dynamics of Spike Timing-Dependent Plasticity in the Somatosensory Cortex.

During development, critical periods of synaptic plasticity facilitate the reordering and refinement of neural connections, allowing the definitive synaptic circuits responsible for correct adult physiology to be established. The L4-L2/3 synapses in the somatosensory cortex (S1) exhibit a presynaptic form of spike timing-dependent long-term depression (t-LTD) that probably fulfills a role in synaptic refinement. This t-LTD persists until the fourth postnatal week in mice, disappearing thereafter.

Vitamin E prevents lipid peroxidation and iron accumulation in PLA2G6-Associated Neurodegeneration.

Background: PLA2G6-Associated Neurodegeneration (PLAN) is a rare neurodegenerative disease with autosomal recessive inheritance, which belongs to the NBIA (Neurodegeneration with Brain Iron Accumulation) group. Although the pathogenesis of the disease remains largely unclear, lipid peroxidation seems to play a central role in the pathogenesis. Currently, there is no cure for the disease.

Long-term effect of neonatal antagonism of ionotropic glutamate receptors on dendritic spines and cognitive function in rats.

Glutamate is the most abundant excitatory neurotransmitter in the hippocampus where mediates its actions by activating glutamate receptors. The activation of these receptors is essential for the maintenance and dynamics of dendritic spines and plasticity that correlate with learning and memory processes during neurodevelopment and adulthood. We studied in adults the effect of blocking ionotropic glutamate receptors (NMDAR, AMPAR, and KAR) functions at neonatal age (PD1-PD15) with their respective antagonists D-AP5, GYKI-53655 and UBP-302.

21st century excitatory amino acid research: A Q & A with Jeff Watkins and Dick Evans.

In 1981 Jeff Watkins and Dick Evans wrote what was to become a seminal review on excitatory amino acids (EAAs) and their receptors (Watkins and Evans, 1981). Bringing together various lines of evidence dating back over several decades on: the distribution in the nervous system of putative amino acid neurotransmitters; enzymes involved in their production and metabolism; the uptake and release of amino acids; binding of EAAs to membranes; the pharmacological action of endogenous excitatory amino acids and their synthetic analogues, and notably the actions of antagonists for the excitations caused by both nerve stimulation and exogenous agonists, often using pharmacological tools developed by Jeff and his colleagues, they provided a compelling account for EAAs, especially l-glutamate, as a bona fide neurotransmitter in the nervous system. The rest, as they say, is history, but far from being consigned to history, EAA research is in rude health well into the 21st Century as this series of Special Issues of Neuropharmacology exemplifies.

Kainate receptor modulation of glutamatergic synaptic transmission in the CA2 region of the hippocampus.

Kainate (KA) receptors (KARs) are important modulators of synaptic transmission. We studied here the role of KARs on glutamatergic synaptic transmission in the CA2 region of the hippocampus where the actions of these receptors are unknown. We observed that KA depresses glutamatergic synaptic transmission at Schaffer collateral-CA2 synapses; an effect that was antagonized by NBQX (a KA/AMPA receptors antagonist) under condition where AMPA receptors were previously blocked.

Metabotropic actions of kainate receptors modulating glutamate release.

Presynaptic kainate (KA) receptors (KARs) modulate GABA and glutamate release in the central nervous system of mammals. While some of the actions of KARs are ionotropic, metabotropic actions for these receptors have also been seen to modulate both GABA and glutamate release. In general, presynaptic KARs modulate glutamate release through their metabotropic actions in a biphasic manner, with low KA concentrations producing an increase in glutamate release and higher concentrations of KA driving weaker release of this neurotransmitter.

Synaptic Plasticity and Oscillations in Alzheimer's Disease: A Complex Picture of a Multifaceted Disease.

Brain plasticity is widely accepted as the core neurophysiological basis of memory and is generally defined by activity-dependent changes in synaptic efficacy, such as long-term potentiation (LTP) and long-term depression (LTD). By using diverse induction protocols like high-frequency stimulation (HFS) or spike-timing dependent plasticity (STDP), such crucial cognition-relevant plastic processes are shown to be impaired in Alzheimer's disease (AD). In AD, the severity of the cognitive impairment also correlates with the level of disruption of neuronal network dynamics.

Kainate receptors: from synaptic activity to disease.

Kainate receptors (KARs) are glutamate receptors that participate in the postsynaptic transmission of information and in the control of neuronal excitability, as well as presynaptically modulating the release of the neurotransmitters GABA and glutamate. These modulatory effects, general follow a biphasic pattern, with low KA concentrations provoking an increase in GABA and glutamate release, and higher concentrations mediating a decrease in the release of these neurotransmitters. In addition, KARs are involved in different forms of long- and short-term plasticity.

HERC1 Ubiquitin Ligase Is Required for Hippocampal Learning and Memory.

Mutations in the human HERC1 E3 ubiquitin ligase protein develop intellectual disability. The () mouse carries a mutation characterized by cerebellar ataxia due of adult cerebellar Purkinje cells death by extensive autophagy. Our previous studies demonstrated that both the neuromuscular junction and the peripheral nerve myelin sheaths are also affected in this mutant.

Challenges in Physiological Phenotyping of hiPSC-Derived Neurons: From 2D Cultures to 3D Brain Organoids.

Neurons derived from human induced pluripotent stem cells (hiPSC-derived neurons) offer novel opportunities for the development of preclinical models of human neurodegenerative diseases (NDDs). Recent advances in the past few years have increased substantially the potential of these techniques and have uncovered new challenges that the field is facing. Here, we outline and discuss challenges related to the functional characterization of hiPSC-derived neurons and propose ways to overcome current difficulties.

Astrocyte-mediated switch in spike timing-dependent plasticity during hippocampal development.

Presynaptic spike timing-dependent long-term depression (t-LTD) at hippocampal CA3-CA1 synapses is evident until the 3 postnatal week in mice, disappearing during the 4 week. At more mature stages, we found that the protocol that induced t-LTD induced t-LTP. We characterized this form of t-LTP and the mechanisms involved in its induction, as well as that driving this switch from t-LTD to t-LTP.