Search results for "Postsynaptic potential"

Alterations in reelin and reelin receptors in Down syndrome.

2019

Reelin is an extracellular matrix glycoprotein that modulates synaptic function and plasticity, with a crucial role in neuronal migration. Changes in the expression of this protein have been reported in neurodegenerative diseases, such as Alzheimer's disease (AD). This molecule is produced by Cajal-Retzius neurons during development and by inhibitory neurons in the adult nervous system. Individuals with Down syndrome (DS) present an early development of AD; therefore, we analyzed the alterations in this molecule and its receptors in the murine model for DS Ts65Dn as well as in human with DS. We performed immunofluorescence analysis for reelin and its receptors very-low-density lipoprotein r…

Binge-like ethanol treatment in adolescence impairs autophagy and hinders synaptic maturation: Role of TLR4.

2018

Abstract Adolescence is a developmental period of brain maturation in which remodeling and changes in synaptic plasticity and neural connectivity take place in some brain regions. A different mechanism participates in adolescent brain maturation, including autophagy processes that play a role in synaptic development and plasticity. Alcohol is a neurotoxic compound whose abuse in adolescence causes TLR4 response activation by triggering neuroinflammation, neural damage and behavioral alterations. However, the potential participation of autophagy in long-term neurochemical and cognitive dysfunctions induced by binge ethanol drinking in adolescence is uncertain. We therefore evaluated whether …

Auxiliary α2δ1 and α2δ3 Subunits of Calcium Channels Drive Excitatory and Inhibitory Neuronal Network Development

2020

VGCCs are multisubunit complexes that play a crucial role in neuronal signaling. Auxiliary α2δ subunits of VGCCs modulate trafficking and biophysical properties of the pore-forming α1 subunit and trigger excitatory synaptogenesis. Alterations in the expression level of α2δ subunits were implicated in several syndromes and diseases, including chronic neuropathic pain, autism, and epilepsy. However, the contribution of distinct α2δ subunits to excitatory/inhibitory imbalance and aberrant network connectivity characteristic for these pathologic conditions remains unclear. Here, we show that α2δ1 overexpression enhances spontaneous neuronal network activity in developing and mature cultures of …

Asymmetry Between Pre- and Postsynaptic Transient Nanodomains Shapes Neuronal Communication.

2020

Synaptic transmission and plasticity are shaped by the dynamic reorganization of signaling molecules within pre- and postsynaptic compartments. The nanoscale organization of key effector molecules has been revealed by single-particle trajectory (SPT) methods. Interestingly, this nanoscale organization is highly heterogeneous. For example, presynaptic voltage-gated calcium channels (VGCCs) and postsynaptic ligand-gated ion channels such as AMPA receptors (AMPARs) are organized into so-called nanodomains where individual molecules are only transiently trapped. These pre- and postsynaptic nanodomains are characterized by a high density of molecules but differ in their molecular organization an…

Astrocyte sodium signaling and the regulation of neurotransmission.

2015

The transmembrane Na(+) concentration gradient is an important source of energy required not only to enable the generation of action potentials in excitable cells, but also for various transmembrane transporters both in excitable and non-excitable cells, like astrocytes. One of the vital functions of astrocytes in the central nervous system (CNS) is to regulate neurotransmitter concentrations in the extracellular space. Most neurotransmitters in the CNS are removed from the extracellular space by Na(+) -dependent neurotransmitter transporters (NeuTs) expressed both in neurons and astrocytes. Neuronal NeuTs control mainly phasic synaptic transmission, i.e., synaptically induced transient pos…

2018

Haplotypes of the Gabra2 gene encoding the α2-subunit of the GABAA receptor (GABAAR) are associated with drug abuse, suggesting that α2-GABAARs may play an important role in the circuitry underlying drug misuse. The genetic association of Gabra2 haplotypes with cocaine addiction appears to be evident primarily in individuals who had experienced childhood trauma. Given this association of childhood trauma, cocaine abuse and the Gabra2 haplotypes, we have explored in a mouse model of early life adversity (ELA) whether such events influence the behavioral effects of cocaine and if, as suggested by the human studies, α2-GABAARs in the nucleus accumbens (NAc) are involved in these perturbed beha…

PTEN recruitment controls synaptic and cognitive function in Alzheimer's models

2016

Dyshomeostasis of amyloid-β peptide (Aβ) is responsible for synaptic malfunctions leading to cognitive deficits ranging from mild impairment to full-blown dementia in Alzheimer's disease. Aβ appears to skew synaptic plasticity events toward depression. We found that inhibition of PTEN, a lipid phosphatase that is essential to long-term depression, rescued normal synaptic function and cognition in cellular and animal models of Alzheimer's disease. Conversely, transgenic mice that overexpressed PTEN displayed synaptic depression that mimicked and occluded Aβ-induced depression. Mechanistically, Aβ triggers a PDZ-dependent recruitment of PTEN into the postsynaptic compartment. Using a PTEN kno…

Endogenous β-neurexins on axons and within synapses show regulated dynamic behavior

2021

Summary: Neurexins are key organizer molecules that regulate synaptic function and are implicated in autism and schizophrenia. β-neurexins interact with numerous cell adhesion and receptor molecules, but their neuronal localization remains elusive. Using single-molecule tracking and high-resolution microscopy to detect neurexin1β and neurexin3β in primary hippocampal neurons from knockin mice, we demonstrate that endogenous β-neurexins are present in fewer than half of excitatory and inhibitory synapses. Moreover, we observe a large extrasynaptic pool of β-neurexins on axons and show that axonal β-neurexins diffuse with higher surface mobility than those transiently confined within synapses…

Putative Role of Taurine as Neurotransmitter During Perinatal Cortical Development

2017

Neurotransmitters and neuronal activity affect neurodevelopmental events like neurogenesis, neuronal migration, apoptosis and differentiation. Beside glutamate and gamma-amino butyric acid, the aminosulfonic acid taurine has been considered as possible neurotransmitter that influences early neuronal development. In this article I review recent studies of our group which demonstrate that taurine can affect a variety of identified neuronal populations in the immature neocortex and directly modulates neuronal activity. These experiments revealed that taurine evoke dose-dependent membrane responses in a variety of neocortical neuron populations, including Cajal-Retzius cells, subplate neurons a…

Extrinsic and intrinsic mechanisms of axon regeneration: the need for spinal cord injury treatment strategies to address both

2016

Spinal cord injury (SCI) causes disturbances in motor and sensory functions leading to paralysis, the severity of which depends on the spinal level of the injury. Traumatic lesions of spinal cord axon projection tracts are untreatable in human patients, although numerous research groups worldwide are studying putative treatment strategies. Both extrinsic factors in the environment of the axons as well as intrinsic factors in the neurons themselves play important roles in the regeneration process (Chew et al., 2012). The peripheral nervous system (PNS) provides a good example where the extrinsic and intrinsic factors play optimally together to allow regeneration. Schwann cells dedifferentiat…