The autism-associated loss of δ-catenin functions disrupts social behavior.

δ-catenin is expressed in excitatory synapses and functions as an anchor for the glutamatergic AMPA receptor (AMPAR) GluA2 subunit in the postsynaptic density. The glycine 34 to serine (G34S) mutation in the gene has been found in autism spectrum disorder (ASD) patients and results in loss of δ-catenin functions at excitatory synapses, which is presumed to underlie ASD pathogenesis in humans. However, how the G34S mutation causes loss of δ-catenin functions to induce ASD remains unclear.

The autism-associated loss of δ-catenin functions disrupts social behaviors.

Unlabelled: δ-catenin is expressed in excitatory synapses and functions as an anchor for the glutamatergic AMPA receptor (AMPAR) GluA2 subunit in the postsynaptic density. The glycine 34 to serine (G34S) mutation in the gene is found in autism spectrum disorder (ASD) patients and induces loss of δ-catenin functions at excitatory synapses, which is presumed to underlie ASD pathogenesis in humans. However, how the G34S mutation causes loss of δ-catenin functions to induce ASD remains unclear.

Complement Component C3 Loss leads to Locomotor Deficits and Altered Cerebellar Internal Granule Cell In Vitro Synaptic Protein Expression in C57BL/6 Mice.

Complement component 3 (C3) expression is increased in the cerebellum of aging mice that demonstrate locomotor impairments and increased excitatory synapse density. However, C3 regulation of locomotion, as well as C3 roles in excitatory synapse function, remains poorly understood. Here, we demonstrate that constitutive loss of C3 function in mice evokes a locomotor phenotype characterized by decreased speed, increased active state locomotor probability, and gait ataxia.

Novel phospho-switch function of delta-catenin in dendrite development.

In neurons, dendrites form the major sites of information receipt and integration. It is thus vital that, during development, the dendritic arbor is adequately formed to enable proper neural circuit formation and function. While several known processes shape the arbor, little is known of those that govern dendrite branching versus extension.

Mechanisms of axon polarization in pyramidal neurons.

Neurons are highly polarized cells that have specialized regions for synaptic input, the dendrites, and synaptic output, the axons. This polarity is critical for appropriate neural circuit formation and function. One of the central gaps in our knowledge is understanding how developing neurons initiate axon polarity.

δ-Catenin engages the autophagy pathway to sculpt the developing dendritic arbor.

The development of the dendritic arbor in pyramidal neurons is critical for neural circuit function. Here, we uncovered a pathway in which δ-catenin, a component of the cadherin-catenin cell adhesion complex, promotes coordination of growth among individual dendrites and engages the autophagy mechanism to sculpt the developing dendritic arbor. Using a rat primary neuron model, time-lapse imaging, immunohistochemistry, and confocal microscopy, we found that apical and basolateral dendrites are coordinately sculpted during development.

A selective role for a component of the autophagy pathway in coupling the Golgi apparatus to dendrite polarity in pyramidal neurons.

Pyramidal neurons have a characteristic morphology that is critical to their ability to integrate into functional neural circuits. In addition to axon dendrite polarity, pyramidal neurons also exhibit dendritic polarity such that apical and basolateral dendrites differ in size, structure and inputs. Dendrite polarity in pyramidal neurons coincides with polarity of the Golgi apparatus, a key feature relevant to directed secretory trafficking, both in vitro and in vivo.

Neuron-Type Specific Loss of CDKL5 Leads to Alterations in mTOR Signaling and Synaptic Markers.

CDKL5 disorder is a devastating neurodevelopmental disorder associated with epilepsy, developmental retardation, autism, and related phenotypes. Mutations in the CDKL5 gene, encoding CDKL5, have been identified in this disorder. CDKL5 is a protein with homology to the serine-threonine kinases and incompletely characterized function.

A role for proteolytic regulation of δ-catenin in remodeling a subpopulation of dendritic spines in the rodent brain.

Neural wiring and activity are essential for proper brain function and behavioral outputs and rely on mechanisms that guide the formation, elimination, and remodeling of synapses. During development, it is therefore vital that synaptic densities and architecture are tightly regulated to allow for appropriate neural circuit formation and function. δ-Catenin, a component of the cadherin-catenin cell adhesion complex, has been demonstrated to be a critical regulator of synaptic density and function in the developing central neurons.

In the Telencephalon, GluN2C NMDA Receptor Subunit mRNA is Predominately Expressed in Glial Cells and GluN2D mRNA in Interneurons.

N-methyl-D-aspartate receptors (NMDARs) are widely distributed in the brain with high concentrations in the telencephalon where they modulate synaptic plasticity, working memory, and other functions. While the actions of the predominate GluN2 NMDAR subunits, GluN2A and GluN2B are relatively well understood, the function of GluN2C and GluN2D subunits in the telencephalon is largely unknown. To better understand the possible role of GluN2C subunits, we used fluorescence in situ hybridization (FISH) together with multiple cell markers to define the distribution and type of cells expressing GluN2C mRNA.

Intracellular amyloid beta expression leads to dysregulation of the mitogen-activated protein kinase and bone morphogenetic protein-2 signaling axis.

Alzheimer's disease (AD) is a neurodegenerative syndrome classically depicted by the parenchymal accumulation of extracellular amyloid beta plaques. However, recent findings suggest intraneuronal amyloid beta (iAβ1-42) accumulation precedes extracellular deposition. Furthermore, the pathologic increase in iAβ1-42 has been implicated in dysregulation of cellular mechanisms critically important in axonal transport.

Quantitative assessment of neural outgrowth using spatial light interference microscopy.

Optimal growth as well as branching of axons and dendrites is critical for the nervous system function. Neuritic length, arborization, and growth rate determine the innervation properties of neurons and define each cell’s computational capability. Thus, to investigate the nervous system function, we need to develop methods and instrumentation techniques capable of quantifying various aspects of neural network formation: neuron process extension, retraction, stability, and branching.

Functional roles of p120ctn family of proteins in central neurons.

The cadherin-catenin complex in central neurons is associated with a variety of cytosolic partners, collectively called catenins. The p120ctn members are a family of catenins that are distinct from the more ubiquitously expressed α- and β-catenins. It is becoming increasingly clear that the functional roles of the p120ctn family of catenins in central neurons extend well beyond their functional roles in non-neuronal cells in partnering with cadherin to regulate adhesion.

Cell density modulates intracellular mass transport in neural networks.

In order to fully understand brain connectivity and elucidate the mechanisms involved in central nervous system disease, the field of neuroscience depends on quantitative studies of neuronal structure and function. Cell morphology and neurite (axonal and dendritic) arborization are typically studied by immunohistochemical and fluorescence techniques. However, dry mass content and intracellular mass transport rates have largely been under-investigated given the inherent difficulties in their measurement.

Halo-free Phase Contrast Microscopy.

We present a new approach for retrieving halo-free phase contrast microscopy (hfPC) images by upgrading the conventional PC microscope with an external interferometric module, which generates sufficient data for reversing the halo artifact. Acquiring four independent intensity images, our approach first measures haloed phase maps of the sample. We solve for the halo-free sample transmission function by using a physical model of the image formation under partial spatial coherence.

Regulation of morphine-induced synaptic alterations: Role of oxidative stress, ER stress, and autophagy.

Our findings suggest that morphine dysregulates synaptic balance in the hippocampus, a key center for learning and memory, via a novel signaling pathway involving reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, and autophagy. We demonstrate in this study that exposure of morphine to hippocampal neurons leads to a reduction in excitatory synapse densities with a concomitant enhancement of inhibitory synapse densities via activation of the μ opioid receptor. Furthermore, these effects of morphine are mediated by up-regulation of intracellular ROS from NADPH oxidase, leading, in turn, to sequential induction of ER stress and autophagy.

Age-related changes in cerebellar and hypothalamic function accompany non-microglial immune gene expression, altered synapse organization, and excitatory amino acid neurotransmission deficits.

We describe age-related molecular and neuronal changes that disrupt mobility or energy balance based on brain region and genetic background. Compared to young mice, aged C57BL/6 mice exhibit marked locomotor (but not energy balance) impairments. In contrast, aged BALB mice exhibit marked energy balance (but not locomotor) impairments.

Interplay of endoplasmic reticulum stress and autophagy in neurodegenerative disorders.

The common underlying feature of most neurodegenerative diseases such as Alzheimer disease (AD), prion diseases, Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS) involves accumulation of misfolded proteins leading to initiation of endoplasmic reticulum (ER) stress and stimulation of the unfolded protein response (UPR). Additionally, ER stress more recently has been implicated in the pathogenesis of HIV-associated neurocognitive disorders (HAND). Autophagy plays an essential role in the clearance of aggregated toxic proteins and degradation of the damaged organelles.

Differential regulation of apical-basolateral dendrite outgrowth by activity in hippocampal neurons.

Hippocampal pyramidal neurons have characteristic dendrite asymmetry, characterized by structurally and functionally distinct apical and basolateral dendrites. The ability of the neuron to generate and maintain dendrite asymmetry is vital, since synaptic inputs received are critically dependent on dendrite architecture. Little is known about the role of neuronal activity in guiding maintenance of dendrite asymmetry.

Cadherins and catenins in dendrite and synapse morphogenesis.

Neurons are highly polarized specialized cells. Neuronal integrity and functional roles are critically dependent on dendritic architecture and synaptic structure, function and plasticity. The cadherins are glycosylated transmembrane proteins that form cell adhesion complexes in various tissues.

δ-Catenin Regulates Spine Architecture via Cadherin and PDZ-dependent Interactions.

The ability of neurons to maintain spine architecture and modulate it in response to synaptic activity is a crucial component of the cellular machinery that underlies information storage in pyramidal neurons of the hippocampus. Here we show a critical role for δ-catenin, a component of the cadherin-catenin cell adhesion complex, in regulating spine head width and length in pyramidal neurons of the hippocampus. The loss of Ctnnd2, the gene encoding δ-catenin, has been associated with the intellectual disability observed in the cri du chat syndrome, suggesting that the functional roles of δ-catenin are vital for neuronal integrity and higher order functions.

Spatially selective photoconductive stimulation of live neurons.

Synaptic activity is intimately linked to neuronal structure and function. Stimulation of live cultured primary neurons, coupled with fluorescent indicator imaging, is a powerful technique to assess the impact of synaptic activity on neuronal protein trafficking and function. Current technology for neuronal stimulation in culture include chemical techniques or microelectrode or optogenetic based techniques.

Mef2 promotes spine elimination in absence of δ-catenin.

δ-Catenin is a component of the cadherin-catenin cell adhesion complex and its loss has been implicated in the mental retardation associated with the Cri du chat syndrome. We have previously demonstrated that loss of δ-catenin in a murine model during development results in excessive spine and synaptic density and function. In order to examine the role of potential molecules that might cooperate with δ-catenin to regulate spine density, we focused on Mef2.