- Neuroscience and Neuropharmacology Research
- Neural dynamics and brain function
- Tryptophan and brain disorders
- Receptor Mechanisms and Signaling
- Circadian rhythm and melatonin
- Memory and Neural Mechanisms
- RNA Research and Splicing
- Ion channel regulation and function
- Mitochondrial Function and Pathology
- Neuroendocrine regulation and behavior
- Ubiquitin and proteasome pathways
- Neuroinflammation and Neurodegeneration Mechanisms
- Retinal Development and Disorders
- Bipolar Disorder and Treatment
- Genomics and Chromatin Dynamics
- Growth Hormone and Insulin-like Growth Factors
- Functional Brain Connectivity Studies
- Photoreceptor and optogenetics research
- Genetic Associations and Epidemiology
- Bioinformatics and Genomic Networks
- Retinoids in leukemia and cellular processes
- Proteoglycans and glycosaminoglycans research
- Neurobiology and Insect Physiology Research
- Signaling Pathways in Disease
- Cholinesterase and Neurodegenerative Diseases
University of Pittsburgh
2013-2024
Lewis University
2024
Austin College
2010-2015
The University of Texas Southwestern Medical Center
2015
Southwestern Medical Center
2015
Kanazawa University
2013
Bristol-Myers Squibb (Japan)
2013
University of Virginia
2000-2003
University of Virginia Health System
2003
U.S. National Science Foundation
2001
Abstract Schizophrenia is associated with disrupted cognitive control and sleep-wake cycles. Here we identify diurnal rhythms in gene expression the human dorsolateral prefrontal cortex (dlPFC), schizophrenia subjects. We find significant (24 h) subjects, however, most of these transcripts are not rhythmic subjects schizophrenia. Instead, have a different set transcripts. The top pathways identified only mitochondrial function. Importantly, drive differential patterns several other genes...
Objective In schizophrenia, alterations in markers of cortical GABA neurotransmission are prominent parvalbumin-containing neurons. Parvalbumin neurons selectively express KCNS3, the gene encoding Kv9.3 potassium channel α-subunit. subunits present voltage-gated channels that contribute to precise detection coincident excitatory synaptic inputs parvalbumin This distinctive feature appears important for synchronization neural networks γ-oscillations. Because impaired prefrontal γ-oscillations...
In primates, working memory function depends on activity in a distributed network of cortical areas that display different patterns delay task-related activity. These differences are correlated with, and might depend on, distinctive properties the neurons located each area. For example, layer 3 pyramidal (L3PNs) differ significantly between primary visual dorsolateral prefrontal (DLPFC) cortices. However, to what extent L3PNs DLPFC other association is less clear. Hence, we compared monkey...
Decades of research have emphasized the importance dopamine (DA) D1 receptor (D1R) mechanisms to dorsolateral prefrontal cortex (dlPFC) working memory function, and hope that D1R agonists could be used treat cognitive disorders. However, existing all had high affinity for D1R, engage β-arrestin signaling, these suppressed task-related neuronal firing. The current study provides first physiological characterization a novel agonist, PF-3628, with low -more similar endogenous DA actions- as...
The shared risk factors and clinical features in schizophrenia bipolar disorder may be linked via mitochondrial dysfunction. However, the severity of dysfunction, and/or specific functional pathways affected, differ between diagnoses, especially at level individual cell types.
Deficits in fast-spiking inhibitory interneurons (FSINs) within the dorsolateral prefrontal cortex (dlPFC) are hypothesized to underlie cognitive impairment associated with schizophrenia. Though representing a minority of interneurons, this key cell type coordinates broad neural network gamma-frequency oscillations, cognition and flexibility. Here we report expression GluN2D mRNA selectively parvalbumin positive cells human postmortem dlPFC tissue, but not pyramidal neurons, little no GluN2C...
The transcription factor CCAAT/enhancer binding protein α (C/EBPα) is the DNA subunit of a multiprotein complex that regulates pituitary-specific GH promoter. C/EBPα absent from GHFT1–5 pituitary progenitor cell line in which ectopic expression leads to activation otherwise dormant Transcriptional regulatory complexes are commonly envisaged as assembling components evenly diffuse throughout nucleoplasm. We show C/EBPα, expressed cells fusion with color variants green fluorescent (GFP),...
The homeodomain protein Pit-1 cooperates with the basic-leucine zipper CCAAT/enhancer binding alpha (C/EBPalpha) to control pituitary-specific prolactin gene transcription. We previously observed that C/EBPalpha was concentrated in regions of centromeric heterochromatin pituitary GHFT1-5 cells and coexpressed redistributed subnuclear sites occupied by Pit-1. Here, we used fluorescence resonance energy transfer microscopy show when recruited Pit-1, average distance separating fluorophores...
Abstract The pituitary-specific homeodomain protein Pit-1 cooperates with other transcription factors, including CCAAT/enhancer binding α (C/EBPα), in the regulation of pituitary lactotrope gene transcription. Here, we correlate cooperative activation prolactin (PRL) by and C/EBPα changes subnuclear localization these factors living cells. Transiently expressed induced PRL GHFT1–5 cells, whereas coexpression HeLa cells demonstrated their cooperativity at promoter. Individually or C/EBPα,...
cAMP signaling has powerful, negative effects on cognitive functions of the primate dorsolateral prefrontal cortex (dlPFC), opening potassium channels to reduce firing and impair working memory, increasing tau phosphorylation in aging neurons. This contrasts with actions classic circuits, where it enhances plasticity transmitter release. PDE4 isozymes regulate actions, thus have been a focus research drug discovery. Previous work focused localization PDE4A PDE4B dlPFC, but PDE4D is also...
Abstract Schizophrenia (SCZ) and bipolar disorder (BP) share a number of features. For example, multiple transcriptome analyses have reported molecular alterations common to both diagnoses, findings supported by the considerable overlap in genetic risk for each disorder. These similarities may underlie certain clinical features that are frequently present disorders. Indeed, many individuals with BP exhibit psychosis, some SCZ prominent mood symptoms warrant diagnosis schizoaffective (SA). To...
In schizophrenia, impaired working memory is associated with transcriptome alterations in layer 3 pyramidal neurons (L3PNs) the dorsolateral prefrontal cortex (DLPFC). Distinct subtypes of L3PNs that send axonal projections to DLPFC opposite hemisphere (callosal projection [CP] neurons) or parietal same (ipsilateral [IP] play critical roles memory. However, how transcriptomes these L3PN might shift during late postnatal development when impairments emerge individuals later diagnosed...
Reciprocal connections between primate dorsolateral prefrontal (DLPFC) and posterior parietal (PPC) cortices, furnished by subsets of layer 3 pyramidal neurons (PNs), contribute to cognitive processes including working memory (WM). A different subset PNs in each region projects the homotopic contralateral hemisphere. These ipsilateral (IP) callosal (CP) projections, respectively, appear be essential for maintenance transfer information during WM. To determine if IP CP differ their...