How Cultured Hippocampal Neurons And Proteins And Rna Transport

In the Summer of 2015 I had the opportunity of accomplishing my own research project. With the help of my graduate student, I led us to better understand the neural pathway

My laboratory focuses on understanding the basic mechanisms of memory storage and aging associated cognitive dysfunction and we are actively trying to develop novel therapeutics for Alzheimer’s disease. Bella is involved in a project that is aimed at elucidating the molecular underpinnings of the establishment and maintenance of excitatory and inhibitory synapses. The molecular mechanisms underlying this process remain elusive. Bella’s goal is to determine whether a specific family of molecular motor proteins, kinesins, plays a critical role in this process. There are about 40 different kinesins and she wanted to identify a specific kinesin that is responsible for the establishment and maintenance of components of excitatory and

Many scientists hypothesize that protein dysfunction plays a role in the progressive damage and death of nerve cells. The nerve cells may be blocked from communication

We assume that if encoding of contextual fear memories require protein synthesis at both hippocampus and PFC, we will be able to identify translationally active mRNAs in hippocampus and PFC. Because RNAs associated with polyribosomes indicate translational activation, we first isolated polyribosomes from mPFC and hippocampus at two time points (one hour and six hours, hereafter T1 and T2

To further understand new protein synthesis at PFC, we asked whether other subregions of PFC are also critical for encoding of contextual fear memories. To address this question, we studied the role of cingulate cortex 1 (CG1) region of PFC in encoding. We injected anisomycin to inhibit protein synthesis at CG1. Four separate groups of animals received anisomycin and saline infusions into the adjacent CG1 (Saline, n= 8; ANI, n=6; Figure 2 C and D). As in the case of Prl cortex, anisomicyn was injected shortly after CFC training. Measurements of freezing at 24 hours

C. APPROACH: Based on our preliminary data on lncRNA changes in specific regions of the brain associated with contextual fear, we hypothesize that specific lncRNAs mediate consolidation and extinction of fear memories. To test this hypothesis, the Puthanveettil and Stackman laboratories will bring together their strong expertise in genomics, bioinformatics, noncoding RNAs, genetics, behavioral models, non-coding RNAs, bioinformatics and functional, in vivo manipulations of novel molecular players. We will employ a research strategy that starts with an unbiased, genome-wide analysis of lncRNAs and funnel down to key players, at which point mechanisms of action will be identified. First, unbiased expression analysis of lncRNAs will be carried out with contextual fear conditioning following extinction of contextual fear memory. Second, we will then carry out in vivo manipulation of specific lncRNAs in specific regions of the brain to determine necessity of the expression of specific lncRNAs in consolidation and extinction of fear memory. We anticipate that our studies will establish the functional importance of candidate lncRNAs in consolidation and extinction and provide novel insights into the novel molecular regulators and mechanisms underlying development of PTSDs. All of the genomics, bioinformatics and rodent behavior analyses will be carried out locally, at Scripps Florida and FAU, with confocal imaging experiments being performed across the street at the Max Planck

During normal development of the mammalian central nervous system (CNS), neural stem cells (NSC) give rise to neurons via process of neurogenesis (Kempermann et al., 2004; Zhao et al., 2008). Neurogenesis normally occurs in dentate gyrus (DG) region of the hippocampus and lateral ventricle of sub-ventricular zone (SVZ) (Zhao et al., 2008). Hippocampal neurogenesis plays pivotal role in neurologic and psychiatric disorder like epilepsy, depression, schizophrenia and mood disorders (Antonova et al., 2004; Keller and Roberts, 2008; Lucassen et al., 2006; Zhao et al., 2008). Development of the nervous system is complex, and includes multistep dynamic processes such as proliferation, differentiation, migration, expansion of axons and dendrites, synapse formation, myelination and programmed cell death (Rice and Barone, 2000). These processes required the coordinated expression of cellular and molecular events in a spatial and temporal manner during the brain development (Rice and Barone, 2000; Rodier, 1994). Several growth factors and signal transduction cascades have been implicated in controlling NSC behavior in the developing brain (Faigle and Song, 2013). Among these, members of the Wnt family of secreted glycoprotein thought to be variably influence proliferation and lineage decisions of NSC and their progeny (Clevers et al., 2014).

We have discovered that contextual fear memories, reliant on synaptic plasticity, altered the expression of specific lncRNAs in two regions of the mouse brain implicated in PTSD, the medial prefrontal cortex (mPFC), and CA1 sub-region of hippocampus. Among the nine lncRNAs we measured, one (GM11549) was upregulated in mPFC and two lncRNAs are regulated in CA1. Our working hypothesis is that the consolidation of contextual fear memory is dependent upon a subset of lncRNAs within the circuit governing fear memories. To test this hypothesis, we will focus on the CA1 region of hippocampus that is critically involved in memory consolidation. We will employ two relevant behavioral model, contextual fear conditioning to achieve the following: (1) Identify specific changes in lncRNAs transcriptome profiles in the CA1 by RNAseq analyses at 30 min, 1 and 6 hrs after training and validate specific changes in lncRNAs by quantitative PCR and confocal imaging. (2) Assess the ability of in vivo intra-CA1 manipulations of specific lncRNAs identified by RNAseq to interfere with the consolidation of fear memory. For these functional studies, we will select the top five lncRNAs based on a fold change of >1.5 (p<0.05) and their sequence homology to humans. (3) Elucidate the mechanism(s) of action of the lncRNAs in the consolidation of fear memory. We anticipate that these studies

Finally, the advent of electron microscopy allowed us to visualise anatomical details at the nano scale. It confirmed the synaptic gap that Sherrington theorised exists, provided incontrovertible validation of the neuron theory, and became a crucial element in many neuroanatomical research that followed (Shepherd, 1991). From these developments, it is hard to deny that the understanding of the anatomy of the neuron and its

families, and that genes likely play a role in the development of the disorder. [...] (IOCDF.)”

Neurological disorders such as Alzheimer’s disease, autism spectrum disorders (ASD), and schizophrenia impact behavior and cognitive processes. While the symptoms for these diseases vary, they share disruptions in synapse development and spine formation. In the mammalian nervous system, dendritic spines are small, dynamic protrusions on neurons that develop in response to increased presynaptic activity. Although spine dynamics throughout development have been well studied, very little is known about the genes involved in spine formation. A recent study in our laboratory discovered spiny projections on a group of inhibitory neurons called DD neurons in C. elegans. Using C. elegans as a model system, the goal of this project is to identify genes responsible for dendritic spine formation. Specifically, I will 1) conduct a forward genetic screen and examine candidate axon guidance molecules to identify genes involved in dendritic spine formation, and 2) examine the effect hyper- and hypo-presynaptic activity has on the development of spines using locomotory changes, such as thrashing and microfluidic assays, and cell-specific changes using channel rhodopsin and temperature sensitive alleles. Given the strong homology between C. elegans and mammalian genes, this research will help identify conserved mechanisms underlying spine formation and maintenance. Ultimately, understanding spine development will help shape the treatment and prevention of

Elly Nedivi, an Associate Professor of Neurobiology at the Picower Institute for Learning and Memory, with the help of her colleagues, discovered that a certain type of brain cell can remodel lost connections, or neural pathways. Previously, researchers had found large-scale changes in dendrite-length, but more importantly, they found that this dendrite growth was limited to a specific type of cell: the interneuron. The cortical neurons they studied showed no significant changes. Unlike sensory or motor neurons that perform specialized functions, interneurons are neurons that form connections between other neurons within the brain.

FMRP is found attached to ribosomes (both free in cytoplasm and attached to endoplasmic reticulum), at the bases of dendrites and within dendritic spines. This is indicative that FMRP may play a role in synaptic function and plasticity.

KD is a very rare disorder, the prevalence thought to be 2 per 100,000 people according to the Cell and Tissue Research article. It is thought that KD is often misdiagnosis as amyotrophic lateral sclerosis (ALS). The first case ever recorded of KD came from a patient who was previously diagnosis with ALS and wanted a seconded opinion. The onset for KD is usually midlife, the range being from 30-60 years of age. The onset is often preceded by non-specific

I have elected to pursue research in the field of neuroscience because I relish the approach of logical thinking to satisfy the curiosity of knowing things about me and the world around me. Neuroscience is a fascinating area with a limitless possibility of understanding and uncovering to resolve so many unanswered and unimagined questions. Although, in recent years, a large number of breakthroughs research have been done in the area of neuroscience, still, there is a lot more to discover and untangle in this area. Such an enormous amount of research work in this area has led open to the advancement in the diagnosis and therapeutic approaches to several neurological disorders and cancer such as glioma. Therefore, I decided