Functions of naturally diverse inhibitory networks in neocortex

Summary

Principal Investigator: Shane R Crandall
Abstract: DESCRIPTION (provided by applicant): Inhibitory neurons play a critical role in normal information processing in the neocortex. Moreover, their dysfunction may contribute to the pathophysiology underlying certain disorders. To date, most of our understanding of the diverse functions of inhibitory neurons and their synapses has been revealed through studies of sensory cortices. My long range goal is to determine if dramatic regional differences in local inhibitory networks result in distinct inhibitory and network mechanisms in the neocortex. My work will specifically focus on the medial prefrontal cortex (mPFC) and ventral postrhinal cortex (vPOR), brain areas with remarkably few parvalbumin- (PV) expressing interneurons compared to sensory cortices. The PFC and POR are essential in cognitive control and visuospatial attention, respectively, and their lack of PV- interneurons could play a pivotal role in how these areas normally process information. There are three specific aims in this proposal: 1) To characterize and compare the local inhibitory networks within the mPFC and vPOR;2) To dissect the cellular mechanisms underlying thalamocortical feedforward inhibition in the mPFC and vPOR;3) To determine the cellular mechanisms underlying gamma oscillations in the mPFC and vPOR. All my data will be compared to data I obtain from the primary somatosensory cortex (SI), a leading model for studying the structure and physiology of neocortical circuits. To address these aims I will use a combination of in vitro patch clamp techniques, various optogenetic approaches, quantitative histological methods, and multiple transgenic lines of mice to identify, select, and manipulate activity of specific neurons. My research will illuminate the basic physiology and diversity of neural circuits in the neocortex. It also may shed light on certain neuropsychiatric conditions in which inhibition is compromised.
Funding Period: 2013-07-01 - 2016-06-30
more information: NIH RePORT

Top Publications

  1. pmc Patch clamp electrophysiology and capillary electrophoresis-mass spectrometry metabolomics for single cell characterization
    Jordan T Aerts
    Beckman Institute for Advanced Science and Technology, Department of Pharmacology, Department of Molecular and Integrative Physiology, Department of Chemistry, and Neuroscience Program, University of Illinois at Urbana Champaign, Urbana, Illinois 61801, United States
    Anal Chem 86:3203-8. 2014

Detail Information

Publications1

  1. pmc Patch clamp electrophysiology and capillary electrophoresis-mass spectrometry metabolomics for single cell characterization
    Jordan T Aerts
    Beckman Institute for Advanced Science and Technology, Department of Pharmacology, Department of Molecular and Integrative Physiology, Department of Chemistry, and Neuroscience Program, University of Illinois at Urbana Champaign, Urbana, Illinois 61801, United States
    Anal Chem 86:3203-8. 2014
    ..The observed differences in the metabolome of these neurons underscore the striking cell to cell heterogeneity in the brain. ..

Research Grants31

  1. Alcoholic liver disease: Biochemical, cellular and systemic responses to ethanol
    Laura E Nagy; Fiscal Year: 2013
    ....
  2. Activity-Dependent Synaptic and Circuit Plasticity
    Robert C Malenka; Fiscal Year: 2013
    ..Such information will lead to a better understanding of the causes of mental illness and eventually to the development of more efficacious treatments. ..
  3. Enduring Effects of Early-Life Serotonin Signaling
    Randy D Blakely; Fiscal Year: 2013
    ..abstract_text> ..
  4. Regulation of CNS viral persistence
    Cornelia Bergmann; Fiscal Year: 2013
    ..Importantly, it will provide valuable information on the interactions of specific CNS cells involved in viral persistence and demyelination and the cellular and soluble mediators of the host immune response...
  5. Cellular mechanisms of GABAergic inhibition in neocortical dendrites
    MICHAEL JAMES HIGLEY; Fiscal Year: 2013
    ..We expect our results will als highlight new avenues into the investigation of the pathophysiology underlying neuropsychiatric disorders resulting from perturbation of both GABAergic and dopaminergic signaling. ..
  6. Genetic targeting of cortical pyramidal neuron subtypes
    Z Josh Huang; Fiscal Year: 2013
    ..1 ..
  7. Inhibitory Circuits Underlying Long-range Sensorimotor Integration
    QIANQUAN SUN; Fiscal Year: 2013
    ..Therefore, unveiling the cortical interneuronal circuit organization will also help o build the groundwork for future dissection of specific interneuronal types, synapses and circuits altered by mental diseases. ..
  8. Functions of conditional Cx36-dependent electrical synapses in the neocortex
    Arthur U Sugden; Fiscal Year: 2013
    ....
  9. Inhibitory regulation of dendritic calcium signals in the prefrontal cortex
    Chiayu Chiu; Fiscal Year: 2013
    ....
  10. Prefrontal anatomic pathways in executive control
    Helen Barbas; Fiscal Year: 2013
    ....
  11. Morphogenesis and function of the cerebral cortex
    Flora M Vaccarino; Fiscal Year: 2013
    ..Both aspects may offer promising leads to correct or reverse the excitatory and inhibitory neuron imbalances that are present in the cerebral cortex of neuropsychiatric and impulse control disorders. ..
  12. Alzheimer's Disease Research Center
    Douglas R Galasko; Fiscal Year: 2013
    ..It will provide an environment and core resources to enhance research, foster professional and community training, and coordinate interdisciplinary research. ..
  13. Functional integration of inhibitory interneuron progenitors in the adult brain
    Robert F Hunt; Fiscal Year: 2013
    ..This study will provide detailed information about the synaptic connectivity of GABAergic progenitor cells after transplant into the adult brain. ..
  14. Molecular Mechanisms of SOD1-linked ALS (P01)
    Joan Selverstone Valentine; Fiscal Year: 2013
    ..This project addresses this question for ALS in particular using some of the best advanced biophysical and biochemical methods available. ..
  15. Epigenome Mapping in Cortical Interneurons
    Schahram Akbarian; Fiscal Year: 2013
    ....
  16. Epigenetic Mechanisms of Depression
    Eric J Nestler; Fiscal Year: 2013
    ..An improved understanding of the molecular basis of depression will lead to improved treatments and diagnostic tests - a high priority for the National Institutes of Health. ..
  17. ENDOTHELIN CONTROL OF RENAL HEMODYNAMIC AND EXCRETORY FUNCTION
    David M Pollock; Fiscal Year: 2013
    ..In particular, this Program will investigate a full range of mechanisms that control ET-1 release and receptor specific actions in order to provide clinically relevant information. ..
  18. Functions of distinct interneuron subtypes in cortical dynamics and behavior
    Adam Kepecs; Fiscal Year: 2013
    ....
  19. Plasticity at the Excitatory Synapse
    Richard L Huganir; Fiscal Year: 2013
    ..Understanding these basic mechanisms of synaptic transmission and plasticity will provide insight into normal and abnormal brain function. ..
  20. Neurocircuitry Underlying DBS Effects in OCD: A Window Into Mechanisms of Action
    Suzanne N Haber; Fiscal Year: 2013
    ..Results from these studies will also make important new contributions to our understanding of the basic mechanisms of DBS. ..
  21. Adolescent marijuana use and maturation of cortical functions
    SYLVINA MULLINS RAVER; Fiscal Year: 2013
    ....
  22. The Role of 5HT3aR GABAergic interneuron in sensory-motor integration in cortex
    SooHyun Lee; Fiscal Year: 2013
    ..These studies will contribute to understanding circuit mechanisms of sensorimotor computation, and serve as a prototype of interareal communication in neocortex. ! ..