Single-nucleotide polymorphism analysis accurately predicts multiple impairments in hippocampal activity and memory performance in a murine model of idiopathic autism.

Autism spectrum disorder (ASD) comprises alterations in brain anatomy and physiology that ultimately affect information processing and behavior. In most cases, autism is considered idiopathic, involving alterations in numerous genes whose functions are not extensively documented. We evaluated the C58/J mouse strain as an idiopathic model of ASD, emphasizing synaptic transmission as the basis of information processing.

Maternal immune activation alters temporal Precision of spike generation of CA1 pyramidal neurons by Unbalancing GABAergic inhibition intheOffspring.

Infection during pregnancy represents a risk factor for neuropsychiatric disorders associated with neurodevelopmental alterations. A growing body of evidence from rodents and non-human primates shows that maternal inflammation induced by viral or bacterial infections results in several neurobiological alterations in the offspring. These changes may play an important role in the pathophysiology of psychiatric disorders like schizophrenia and autism spectrum disorders, whose clinical features include impairments in cognitive processing and social performance.

Dopamine D1 receptors activation rescues hippocampal synaptic plasticity and cognitive impairments in the MK-801 neonatal schizophrenia model.

Schizophrenia is a disorder with a higher cognitive decline in early adulthood, causing impaired retention of episodic memories. However, the physiological and behavioral functions that underlie cognitive deficits with a potential mechanism to ameliorate and improve cognitive performance are unknown. In this study, we used the MK-801 neurodevelopmental schizophrenia-like model.

The bidirectional role of GABAA and GABAB receptors during the differentiation process of neural precursor cells of the subventricular zone.

The intricate process of neuronal differentiation integrates multiple signals to induce transcriptional, morphological, and electrophysiological changes that reshape the properties of neural precursor cells during their maturation and migration process. An increasing number of neurotransmitters and biomolecules have been identified as molecular signals that trigger and guide this process. In this sense, taurine, a sulfur-containing, non-essential amino acid widely expressed in the mammal brain, modulates the neuronal differentiation process.

Postnatal hypofunction of N-methyl-D-aspartate receptors alters perforant path synaptic plasticity and filtering and impairs dentate gyrus-mediated spatial discrimination.

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.

Experimental Approach: We identified a series of synaptic alterations of the lateral and medial perforant paths in animals postnatally treated with the NMDA antagonist MK-801.

Cannabidiol Modifies the Glutamate Over-Release in Brain Tissue of Patients and Rats with Epilepsy: A Pilot Study.

Drug-resistant epilepsy (DRE) is associated with high extracellular levels of glutamate. Studies support the idea that cannabidiol (CBD) decreases glutamate over-release. This study focused on investigating whether CBD reduces the evoked glutamate release in cortical synaptic terminals obtained from patients with DRE as well as in a preclinical model of epilepsy.

BDNF and Lactate as Modulators of Hippocampal CA3 Network Physiology.

Growing evidence supports the notion that brain-derived neurotrophic factor (BDNF) and lactate are potent modulators of mammalian brain function. The modulatory actions of those biomolecules influence a wide range of neuronal responses, from the shaping of neuronal excitability to the induction and expression of structural and synaptic plasticity. The biological actions of BDNF and lactate are mediated by their cognate receptors and specific transporters located in the neuronal membrane.

5-HT Receptors Control GABAergic Transmission and CA1 Pyramidal Cell Output of Dorsal Hippocampus.

The blockade of 5-HT receptors represents an experimental approach that might ameliorate the memory deficits associated with brain disorders, including Alzheimer's disease and schizophrenia. However, the synaptic mechanism by which 5-HT receptors control the GABAergic and glutamatergic synaptic transmission is barely understood. In this study, we demonstrate that pharmacological manipulation of 5-HT receptors with the specific agonist EMD 386088 (7.

Symbiotic Supplementation ( and Agave Inulin) Improves Spatial Memory and Increases Plasticity in the Hippocampus of Obese Rats: A Proof-of-Concept Study.

Obesity has been linked to cognitive impairment through systemic low-grade inflammation. High fat and sugar diets (HFSDs) also induce systemic inflammation, either by induced Toll-like receptor 4 response, or by causing dysbiosis. This study aimed to evaluate the effect of symbiotics supplementation on spatial and working memory, butyrate concentration, neurogenesis, and electrophysiological recovery of HFSD-fed rats.

NMDA receptor activity during postnatal development determines intrinsic excitability and mossy fiber long-term potentiation of CA3 pyramidal cells.

Experimental manipulations that interfere with the functional expression of N-methyl-D-aspartate receptors (NMDARs) during prenatal neurodevelopment or critical periods of postnatal development are models that mimic behavioral and neurophysiological abnormalities of schizophrenia. Blockade of NMDARs with MK-801 during early postnatal development alters glutamate release and impairs the induction of NMDAR-dependent long-term plasticity at the CA1 area of the hippocampus. However, it remains unknown if other forms of hippocampal plasticity, such as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated short- and long-term potentiation, are compromised in response to neonatal treatment with MK-801.

Taurine Promotes Differentiation and Maturation of Neural Stem/Progenitor Cells from the Subventricular Zone via Activation of GABA Receptors.

Neurogenesis, the formation of new neurons in the brain, occurs throughout the lifespan in the subgranular zone of the dentate gyrus and subventricular zone (SVZ) lining the lateral ventricles of the mammal brain. In this process, gamma-aminobutyric acid (GABA) and its ionotropic receptor, the GABA receptor (GABAR), play a critical role in the proliferation, differentiation, and migration process of neural stem/progenitor cells (NPC). Taurine, a non-essential amino acid widely distributed throughout the central nervous system, increases the proliferation of SVZ progenitor cells by a mechanism that may involve GABAR activation.

Maternal immune activation increases excitability via downregulation of A-type potassium channels and reduces dendritic complexity of hippocampal neurons of the offspring.

The epidemiological association between bacterial or viral maternal infections during pregnancy and increased risk for developing psychiatric disorders in offspring is well documented. Numerous rodent and non-human primate studies of viral- or, to a lesser extent, bacterial-induced maternal immune activation (MIA) have documented a series of neurological alterations that may contribute to understanding the pathophysiology of schizophrenia and autism spectrum disorders. Long-term neuronal and behavioral alterations are now ascribed to the effect of maternal proinflammatory cytokines rather than the infection itself.

Systemic administration of lipopolysaccharide induces hyperexcitability of prelimbic neurons via modulation of sodium and potassium currents.

In C57BL/6 J mice, systemic inflammation was induced by administering bacterial LPS (1 mg/kg) intraperitoneally. In response, animals exhibited hypokinesia, piloerection, and a slight decrease in body temperature accompanied by increased serum levels of the proinflammatory cytokine TNF-α. 24 h after the immunogenic challenge, acute cortical slices were prepared, and whole-cell patch-clamp recordings were performed in morphologically identified prelimbic neurons of the mice's prefrontal cortex.

Long-Term Functional and Cytoarchitectonic Effects of the Systemic Administration of the Histamine H Receptor Antagonist/Inverse Agonist Chlorpheniramine During Gestation in the Rat Offspring Primary Motor Cortex.

The transient histaminergic system is among the first neurotransmitter systems to appear during brain development in the rat mesencephalon/rhombencephalon. Histamine increases FOXP2-positive deep-layer neuron differentiation of cortical neural stem cells through H receptor activation . The or systemic administration of chlorpheniramine (H receptor antagonist/inverse agonist) during deep-layer cortical neurogenesis decreases FOXP2 neurons in the developing cortex, and HR- or histidine decarboxylase-knockout mice show impairment in learning and memory, wakefulness and nociception, functions modulated by the cerebral cortex.

Biophysical and synaptic properties of regular spiking interneurons in hippocampal area CA3 of aged rats.

Neuronal processing from the dentate gyrus to the hippocampus is critical for storage and recovery of new memory traces. In area CA3, GABAergic interneurons form a strong barrage of inhibition that modulates pyramidal cells. A well-established feature of aging is decreased GABAergic inhibition, a phenomenon that contributes to the exacerbated excitability of aged pyramidal cells.

Activation of D1/D5 receptors ameliorates decreased intrinsic excitability of hippocampal neurons induced by neonatal blockade of N-methyl-d-aspartate receptors.

Background And Purpose: Dysregulation of dopaminergic transmission combined with transient hypofunction of N-methyl-d-aspartate receptors (NMDARs) is a key mechanism that may underlie cognitive symptoms of schizophrenia.

Experimental Approach: Therefore, we aimed to identify electrophysiologic alterations in animals neonatally treated with the NMDA receptor antagonist, MK-801, or with saline solution.

Key Results: Patch-clamp whole-cell recordings from MK-801-treated animals revealed altered passive and active electrophysiologic properties compared with CA1 pyramidal cells from saline-treated animals, including up-regulation of the K inward-rectifier conductance and fast-inactivating and slow/non-inactivating K currents.

Lactate induces synapse-specific potentiation on CA3 pyramidal cells of rat hippocampus.

Neuronal activity within the physiologic range stimulates lactate production that, via metabolic pathways or operating through an array of G-protein-coupled receptors, regulates intrinsic excitability and synaptic transmission. The recent discovery that lactate exerts a tight control of ion channels, neurotransmitter release, and synaptic plasticity-related intracellular signaling cascades opens up the possibility that lactate regulates synaptic potentiation at central synapses. Here, we demonstrate that extracellular lactate (1-2 mM) induces glutamatergic potentiation on the recurrent collateral synapses of hippocampal CA3 pyramidal cells.

Functional expression of TrkB receptors on interneurones and pyramidal cells of area CA3 of the rat hippocampus.

The dentate gyrus and hippocampal area CA3 region of the mammalian brain contains the highest levels of brain-derived neurotrophic factor (BDNF) and its canonical membrane receptor, tropomyosin-related kinase B (TrkB). Therefore, the present study examines the expression and physiological responses triggered by activation of TrkB on hippocampal area CA3 interneurones and pyramidal cells of the rat hippocampus. Triple immunolabelling for TrkB, glutamate decarboxylase 67, and the calcium-binding proteins parvalbumin, calbindin or calretinin confirms the somatic expression of TrkB in all CA3 sublayers.

Impaired Cortical Cytoarchitecture and Reduced Excitability of Deep-Layer Neurons in the Offspring of Diabetic Rats.

Maternal diabetes has been related to low verbal task scores, impaired fine and gross motor skills, and poor performance in graphic and visuospatial tasks during childhood. The primary motor cortex is important for controlling motor functions, and embryos exposed to high glucose show changes in cell proliferation, migration, and differentiation during corticogenesis. However, the existing studies do not discriminate between embryos with or without neural tube defects, making it difficult to conclude whether the reported changes are related to neural tube defects or other anomalies.

Minocycline prevents neuronal hyperexcitability and neuroinflammation in medial prefrontal cortex, as well as memory impairment caused by repeated toluene inhalation in adolescent rats.

Toluene can be intentionally misused by adolescents to experience psychoactive effects. Toluene has a complex mechanism of action and broad behavioral effects, among which memory impairment is reported consistently. We have previously reported that repeated toluene inhalation (8000 ppm) increases layer 5 prelimbic pyramidal cells' excitability in the medial prefrontal cortex (mPFC) of adolescent rats.

Metabotropic Glutamate Receptors at the Aged Mossy Fiber - CA3 Synapse of the Hippocampus.

Metabotropic glutamate receptors (mGluRs) are a group of G-protein-coupled receptors that exert a broad array of modulatory actions at excitatory synapses of the central nervous system. In the hippocampus, the selective activation of the different mGluRs modulates the intrinsic excitability, the strength of synaptic transmission, and induces multiple forms of long-term plasticity. Despite the relevance of mGluRs in the normal function of the hippocampus, we know very little about the changes that mGluRs functionality undergoes during the non-pathological aging.

Repeated toluene exposure alters the synaptic transmission of layer 5 medial prefrontal cortex.

Toluene is an organic solvent commonly misused by inhalation among adolescents to experience psychoactive effects. Repeated toluene exposure produces several cognitive deficits, including working memory impairment in which the medial prefrontal cortex (mPFC) plays a central role. Among other effects, toluene antagonizes NMDA receptors, enhance GABA receptor-mediated responses and increases dopamine release.

Progressive Alterations in Synaptic Transmission and Plasticity of Area CA1 Precede the Cognitive Impairment Associated with Neonatal Administration of MK-801.

Transient hypofunction of NMDA receptors during brain maturation has been linked to cellular and behavioral alterations that mirror symptoms of schizophrenia. In line with this notion, neonatal administration of the non-competitive NMDA receptor antagonist, MK-801, mimics the negative and cognitive symptoms of schizophrenia. By combining behavioral evaluations with extracellular recordings in acute hippocampal slices, we uncovered a progressive alteration of synaptic transmission of animals neonatally treated with MK-801.

Probiotics and Prebiotics as a Therapeutic Strategy to Improve Memory in a Model of Middle-Aged Rats.

Aging is associated with morphological, physiological and metabolic changes, leading to multiorgan degenerative pathologies, such as cognitive function decline. It has been suggested that memory loss also involves a decrease in neurotrophic factors, including brain-derived neurotrophic factor (BDNF). In recent years, microbiota has been proposed as an essential player in brain development, as it is believed to activate BDNF secretion through butyrate production.