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You searched for +publisher:"University of Alabama – Birmingham" +contributor:("Sweatt, J. David<br>"). Showing records 1 – 3 of 3 total matches.

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1. Rubio, Maria Dolores. Myosin II in hippocampal synapses: regulation of synaptic plasticity, strength and actin dynamics by two distinct isoforms.

Degree: PhD, 2011, University of Alabama – Birmingham

Cytoskeletal actin filaments underlie dendritic spine plasticity, critical for several forms of learning and memory. Therefore, understanding the mechanisms that regulate actin dynamics is essential to elucidate memory formation pathways. Myosins, a superfamily of actin binding proteins, have emerged as candidates for regulation of actin dynamics in the brain. Several myosin class II isoforms have been identified in brain, but their individual contribution to synaptic activity is still unknown. Based on the finding that myosin IIB regulates actin polymerization in the growth cone of developing neurons and that it is necessary for maintenance of dendritic spine structure, I hypothesized that in dendritic spines myosin IIB regulates actin dynamics, affecting synaptic transmission. I show that in addition to basal transmission, myosin IIB affects the maintenance of long term potentiation through a mechanism leading to reorganization and de novo synthesis of actin filaments. I further show that myosin IIB activity on actin filaments is critical for long-term memory consolidation. In addition to advancing our understanding of myosin IIB function in neurons, I was also able to characterize and identify a distinct muscle isoform of myosin II, MyH7B, in brain. The effects on dendritic spine morphology and synaptic strength of this isoform are different from those of myosin IIB. MyH7B acts as a structural myosin that maintains synaptic morphology and regulates trafficking of AMPA receptors to the synaptic surface through its activity on actin filament dynamics. Through my research I was able to identify a novel function for two distinct myosin II isoforms in brain, finding them critical for synaptic activity.

1 online resource (viii, 205 p. : ill., digital, PDF file)

Neurobiology;

Joint Health Sciences;

actin myosin dendritic spine synaptic transmission AMPA receptors plasticity

UNRESTRICTED

Advisors/Committee Members: Rumbaugh, Gavin, McMahon, Lori L.<br>, Sontheimer, Harald<br>, Sweatt, J. David<br>, Wilson, Scott.

Subjects/Keywords: Actins  – metabolism<; br>; Cardiac Myosins  – physiology<; br>; Long-Term Potentiation  – physiology<; br>; Memory  – physiology<; br>; Myosin Heavy Chains  – physiology<; br>; Neurons  – metabolism<; br>; Nonmuscle Myosin Type IIB  – metabolism<; br>; Synapses  – physiology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Rubio, M. D. (2011). Myosin II in hippocampal synapses: regulation of synaptic plasticity, strength and actin dynamics by two distinct isoforms. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,878

Chicago Manual of Style (16th Edition):

Rubio, Maria Dolores. “Myosin II in hippocampal synapses: regulation of synaptic plasticity, strength and actin dynamics by two distinct isoforms.” 2011. Doctoral Dissertation, University of Alabama – Birmingham. Accessed October 19, 2019. http://contentdm.mhsl.uab.edu/u?/etd,878.

MLA Handbook (7th Edition):

Rubio, Maria Dolores. “Myosin II in hippocampal synapses: regulation of synaptic plasticity, strength and actin dynamics by two distinct isoforms.” 2011. Web. 19 Oct 2019.

Vancouver:

Rubio MD. Myosin II in hippocampal synapses: regulation of synaptic plasticity, strength and actin dynamics by two distinct isoforms. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2011. [cited 2019 Oct 19]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,878.

Council of Science Editors:

Rubio MD. Myosin II in hippocampal synapses: regulation of synaptic plasticity, strength and actin dynamics by two distinct isoforms. [Doctoral Dissertation]. University of Alabama – Birmingham; 2011. Available from: http://contentdm.mhsl.uab.edu/u?/etd,878

2. Funk, Adam J. Intracellular signaling abnormalities in schizophrenia.

Degree: PhD, 2011, University of Alabama – Birmingham

The pathophysiology of schizophrenia is complex and diverse, with many classes of receptors, neurotransmitters, and brain regions implicated in this illness. The many hypotheses proposed have yet to fully explain the heterogeneity of the genetic, postmor-tem, and clinical evidence. It is the goal of this dissertation to integrate the current hy-potheses of schizophrenia into a unified hypothesis of abnormal intracellular signaling and signal integration. Inconsistencies in genetic and postmortem findings suggest that the development of schizophrenia is multifaceted, and the heterogeneity of symptoms supports the hypothesis of any number of intracellular signaling abnormalities as the pre-cipitating factor in the development of this devastating illness. In this dissertation I ex-amined conserved intracellular signaling pathways for activation (via phosphorylation of kinases) and functional outcome (via phosphorylation of proteins with known functional consequences). Abnormal protein expression in the MAPK pathway includes decreased SynGAP, Rap2, JNK1/2, and PSD-95 in the anterior cingulate cortex (ACC). Abnormal activation, determined by phosphorylation, of the MAPK pathway includes decreased pThr183/Tyr185 JNK1/2 and pSer295 PSD-95 in the ACC in schizophrenia. Abnormal protein expression in the cAMP pathway includes increased RACK1, Fyn, and Cdk5 in the dorsolateral prefrontal cortex (DLPFC) in schizophrenia. Abnormal function, deter-mined by phosphorylation, of the cAMP pathway includes increased pTyr1336 NR2B and pSer295 PSD-95 in the DLPFC in schizophrenia. Signaling through G protein coupled receptors (GPCRs) is regulated by G protein-coupled receptor kinases (GRKs). I measured the protein and mRNA expression of GRKs 2-6 in the anterior cingulate cortex. I found increased transcript expression for GRK2 and GRK5, and increased protein ex-pression for GRK5. The abnormalities in GPCR regulation, coupled with alterations of signaling cascades downstream of these proteins suggest that dysfunction of intracellular signaling and signal integration contribute to the pathophysiology of schizophrenia.

1 online resource (xii, 158 p.) : ill., digital, PDF file.

Neurobiology

Joint Health Sciences

Schizophrenia signaling MAPK cAMP GRK phosphorylation

UNRESTRICTED

Advisors/Committee Members: McCullumsmith, Robert E., Sweatt, J. David<br>, Thiebert, Anne<br>, Cowell, Rita<br>, Meador-Woodruff, James H..

Subjects/Keywords: Carrier Proteins  – metabolism<; br>; GTPase-Activating Proteins  – metabolism<; br>; Gyrus Cinguli  – metabolism<; br>; Intracellular Signaling Peptides and Proteins  – metabolism<; br>; Membrane Proteins  – metabolism<; br>; Prefrontal Cortex  – metabolism<; br>; Schizophrenia  – metabolism

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APA (6th Edition):

Funk, A. J. (2011). Intracellular signaling abnormalities in schizophrenia. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,1151

Chicago Manual of Style (16th Edition):

Funk, Adam J. “Intracellular signaling abnormalities in schizophrenia.” 2011. Doctoral Dissertation, University of Alabama – Birmingham. Accessed October 19, 2019. http://contentdm.mhsl.uab.edu/u?/etd,1151.

MLA Handbook (7th Edition):

Funk, Adam J. “Intracellular signaling abnormalities in schizophrenia.” 2011. Web. 19 Oct 2019.

Vancouver:

Funk AJ. Intracellular signaling abnormalities in schizophrenia. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2011. [cited 2019 Oct 19]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,1151.

Council of Science Editors:

Funk AJ. Intracellular signaling abnormalities in schizophrenia. [Doctoral Dissertation]. University of Alabama – Birmingham; 2011. Available from: http://contentdm.mhsl.uab.edu/u?/etd,1151

3. Gavin, Cristin. Myosin Ii Regulates Actin Dynamics Critical For Structural Plasticity And Fear Memory Formation.

Degree: PhD, 2012, University of Alabama – Birmingham

Dynamic changes to the actin cytoskeleton are required for synaptic plasticity and long-term memory formation. However, the molecular mechanisms that mediate filamentous actin (F-actin) dynamics during both activity-dependent synaptic potentiation and long-term memory encoding are poorly understood. Myosin II motor proteins are highly expressed in actin-rich growth structures in neurons, including dendritic spines. Recent work demonstrates that these molecular machines mobilize F-actin in response to synaptic stimulation and are required for memory encoding in CA1 hippocampus of rodents. The aims of this project were two-fold. First, we sought to establish if myosin II regulates actin filament polymerization necessary for structural plasticity at individual synapses. To test this, we targeted single hippocampal spines in acute slices from GFP M line mice. Using 2-photon laser scanning microscopy (LSM) combined with targeted glutamate uncaging, we were able to evaluate the effects of myosin II motor activity on activity-dependent single spine plasticity. We found that myosin II potently regulates an early cytoskeletal-dependent processes that is critical for inducing and later stabilizing changes in spine volume. These studies provide a critical mechanistic link between glutamate receptor activation and de novo F-actin polymerization known to regulate dendritic spine structural plasticity, a process believed to underlie aspects of memory and cognition. The hippocampus and lateral amygdala (LA) share many molecular mechanisms of synaptic potentiation and memory formation. Because myosin II-dependent actin regulation is critical for structural and functional plasticity at CA1 synapses, as well as for long-term fear memory formation (LTM), we hypothesized that myosin II regulates an actin-dependent mechanism required for amygdala-dependent fear memory formation. To test this, we trained rats using a cued-fear conditioning paradigm combined with targeted intra-cranial infusions of small molecule inhibitors at different time points. We found that myosin II motors are critical for an early actin-dependent process that selectively facilitates long-term fear memory consolidation. Furthermore, using viral-mediated in vivo knockdown, we identified the IIB isoform of myosin as the critical regulator of this process. Taken together, these data support the idea that myosin II-dependent actin regulation is a general mechanism that supports memory consolidation in the mammalian CNS.

PhD

1 online resource (xi, 136 p.) :ill., digital, PDF file.

Neurobiology

Joint Health Sciences

actin long term memory myosin II single spine glutamate uncaging structural plasticity

UNRESTRICTED

Advisors/Committee Members: Gavin Rumbaugh, McMahon,Lori Sweatt,J. David Wadiche, Jacques I. Wilson,Scott.

Subjects/Keywords: Bone Neoplasms – secondary<; br>; Breast Neoplasms – pathology<; br>; Cell Communication<; br>; Cyclic AMP-Dependent Protein Kinases – metabolism.<; br>; Gap Junctions – metabolism.<; br>; Osteoblasts – cytology.<; br>; Phosphatidylinositol 3-Kinases – metabolism.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Gavin, C. (2012). Myosin Ii Regulates Actin Dynamics Critical For Structural Plasticity And Fear Memory Formation. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,1396

Chicago Manual of Style (16th Edition):

Gavin, Cristin. “Myosin Ii Regulates Actin Dynamics Critical For Structural Plasticity And Fear Memory Formation.” 2012. Doctoral Dissertation, University of Alabama – Birmingham. Accessed October 19, 2019. http://contentdm.mhsl.uab.edu/u?/etd,1396.

MLA Handbook (7th Edition):

Gavin, Cristin. “Myosin Ii Regulates Actin Dynamics Critical For Structural Plasticity And Fear Memory Formation.” 2012. Web. 19 Oct 2019.

Vancouver:

Gavin C. Myosin Ii Regulates Actin Dynamics Critical For Structural Plasticity And Fear Memory Formation. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2012. [cited 2019 Oct 19]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,1396.

Council of Science Editors:

Gavin C. Myosin Ii Regulates Actin Dynamics Critical For Structural Plasticity And Fear Memory Formation. [Doctoral Dissertation]. University of Alabama – Birmingham; 2012. Available from: http://contentdm.mhsl.uab.edu/u?/etd,1396

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