Project 1 (P1) provides molecular tests at the cell type-specific level for the following aspects of the Central Hypothesis: 1) a core cortical pathology in schizophrenia affects layer 3 pyramidal cells, and 2) the impact of this pathology on gene expression is moderated by factors that differ across cortical regions. Layer 3 pyramidal cells will be collected using laser microdissection in postmortem samples from subjects with schizophrenia or schizoaffective disorder and healthy comparison subjects (Aim 1). Within-region analyses will inform on the cell autonomous pathology of layer 3 pyramidal cells in schizophrenia. Across-region analyses will characterize molecular regional specificities in control subjects and how they impact the pathology of layer 3 pyramidal cells in schizophrenia. A secondary goal is to gain insight into potential molecular targets to restore functional balance along the visual working memory and attention network. Accordingly, since layer 3 pyramidal cell alterations are predicted to induce transcriptional responses in the parvalbumin (PV)-containing GABA neurons that they innervate, similar analyses will be performed in PV neurons (Aim 2). To provide a comprehensive molecular perspective on coordinated local circuit alterations, expression of genes (mRNA) and gene regulatory micro-RNAs (miRNA) will be investigated in parallel (Aims 1-2) and biological modules implicated in healthy control and pathological conditions will be identified by changes in coordinated expression across cell types, regions and cohorts (Aim 3). Results from PI will inform all other Center projects on the molecular and cellular bases in regards to the Central Hypothesis that regional differences moderate the serverity of layer 3 PC alterations in schizophrenia. PI will also provide molecular leads for protein marker studies in P2, and for layer 3 PC regional differences in electrophysiological properties in P3. Together Projects 1-3 will provide the molecular, cellular and circuitry bases for the functional connectivity studies in monkey (P4), and in imaging studies of healthy controls and subjects with schizophrenia (P5).
This project will characterize at the cellular level the core molecular pathology in cortical layer 3 pyramidal cells in schizophrenia and determine how this pathology is moderated by factors that include regional specificity in the expression of mRNAs and miRNA regulatory elements. Project 1 will also provide insight into potential targets to restore functional balance along the visual cortical network.
|Yan, Zhen; Kim, Eunjoon; Datta, Dibyadeep et al. (2016) Synaptic Actin Dysregulation, a Convergent Mechanism of Mental Disorders? J Neurosci 36:11411-11417|
|Murty, Vishnu P; Calabro, Finnegan; Luna, Beatriz (2016) The role of experience in adolescent cognitive development: Integration of executive, memory, and mesolimbic systems. Neurosci Biobehav Rev 70:46-58|
|Ramachandran, Suchitra; Meyer, Travis; Olson, Carl R (2016) Prediction suppression in monkey inferotemporal cortex depends on the conditional probability between images. J Neurophysiol 115:355-62|
|Datta, Dibyadeep; Arion, Dominique; Roman, Kaitlyn M et al. (2016) Altered Expression of ARP2/3 Complex Signaling Pathway Genes in Prefrontal Layer 3 Pyramidal Cells in Schizophrenia. Am J Psychiatry :appiajp201616020204|
|Chung, Daniel W; Fish, Kenneth N; Lewis, David A (2016) Pathological Basis for Deficient Excitatory Drive to Cortical Parvalbumin Interneurons in Schizophrenia. Am J Psychiatry 173:1131-1139|
|Hall, Nathan J; Colby, Carol L (2016) Express saccades and superior colliculus responses are sensitive to short-wavelength cone contrast. Proc Natl Acad Sci U S A 113:6743-8|
|Chung, Daniel W; Volk, David W; Arion, Dominique et al. (2016) Dysregulated ErbB4 Splicing in Schizophrenia: Selective Effects on Parvalbumin Expression. Am J Psychiatry 173:60-8|
|Aminoff, Elissa M; Li, Yuanning; Pyles, John A et al. (2016) Associative hallucinations result from stimulating left ventromedial temporal cortex. Cortex 83:139-44|
|Hoftman, Gil D; Datta, Dibyadeep; Lewis, David A (2016) Layer 3 Excitatory and Inhibitory Circuitry in the Prefrontal Cortex: Developmental Trajectories and Alterations in Schizophrenia. Biol Psychiatry :|
|Chen, Cho-Yi; Logan, Ryan W; Ma, Tianzhou et al. (2016) Effects of aging on circadian patterns of gene expression in the human prefrontal cortex. Proc Natl Acad Sci U S A 113:206-11|
Showing the most recent 10 out of 17 publications