The present program project centers around three independent proposals aimed at understanding the development, function and plasticity of 5HT3aR interneurons (INs) in the cerebral cortex. The impetus to create this core emerged out of the recognition that a shared molecular and transgenic resource would serve the dual purpose of cost efficiency in the production and distribution of a shared set of reagents and to foster a natural setting for collaboration between the three contributing laboratories. Indeed, the use of the same genetic tools across each of the proposals provides for a solid basis by which results garnered through diverse methods and collected at different time points from both developing and mature animals can be compared. To implement these goals we recognize that two distinct considerations need to be taken into account in assembling this core. First, (in Phase 1) we need to scale up the availability of a set of existing reagents that are broadly required for the execution of the aims of each of the constituent projects. From the judicious collection of preexisting reagents, we have assembled our preliminary data. Although lacking sufficient specificity to individually target each of the five classes of 5HT3aR INs we wish to study, we already possessed the ability to label this population in its entirety using the 5HT3aRcre driver line, as well as to selectively examine the VIP+ versus VIP- subpopulations that separate the entire 5HT3aR pool into two distinct subgroups using the VIPcre driver line in conjunction with the 5HT3aR-EGFP line. In addition, the Chatcre driver allows us to;with reasonable fidelity target the VIP+/CR+ bipolar population. In combination with a series of conditional alleles, reporters and viral effectors, with the establishment of Core A, we will have in hand the tools to at a general level address all aims in our proposal. In Phase 2 of this proposal we wish to increase the fidelity of our analysis by developing a refined set of alleles and viral reagents to more specifically label and manipulate discrete subsets of the 5HT3aR+ IN population. , Hence, having produced (or collected) such reagents during the first two years of our proposal, we wish in the second portion of the core's existence (years 3-5) to utilize these tools in a finer grained analysis of these IN subtypes.

Public Health Relevance

By developing a centralized infrastructure, the efficiency in generation of these reagents can be done most economically. It also provides a centralized resource for distribution, first and foremost to the members of the PPG but ultimately to the community at large.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS074972-02
Application #
8551745
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
2018-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
2
Fiscal Year
2013
Total Cost
$304,585
Indirect Cost
$124,357
Name
New York University
Department
Type
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Tuncdemir, Sebnem N; Wamsley, Brie; Stam, Floor J et al. (2016) Early Somatostatin Interneuron Connectivity Mediates the Maturation of Deep Layer Cortical Circuits. Neuron 89:521-35
Tremblay, Robin; Lee, Soohyun; Rudy, Bernardo (2016) GABAergic Interneurons in the Neocortex: From Cellular Properties to Circuits. Neuron 91:260-92
Ma, Lei; Qiao, Qian; Tsai, Jin-Wu et al. (2016) Experience-dependent plasticity of dendritic spines of layer 2/3 pyramidal neurons in the mouse cortex. Dev Neurobiol 76:277-86
Qiao, Qian; Ma, Lei; Li, Wei et al. (2016) Long-term stability of axonal boutons in the mouse barrel cortex. Dev Neurobiol 76:252-61
Petros, Timothy J; Bultje, Ronald S; Ross, M Elizabeth et al. (2015) Apical versus Basal Neurogenesis Directs Cortical Interneuron Subclass Fate. Cell Rep 13:1090-5
Cichon, Joseph; Gan, Wen-Biao (2015) Branch-specific dendritic Ca(2+) spikes cause persistent synaptic plasticity. Nature 520:180-5
Tuncdemir, Sebnem N; Fishell, Gord; Batista-Brito, Renata (2015) miRNAs are Essential for the Survival and Maturation of Cortical Interneurons. Cereb Cortex 25:1842-57
Miyoshi, Goichi; Young, Allison; Petros, Timothy et al. (2015) Prox1 Regulates the Subtype-Specific Development of Caudal Ganglionic Eminence-Derived GABAergic Cortical Interneurons. J Neurosci 35:12869-89
De Marco García, Natalia V; Priya, Rashi; Tuncdemir, Sebnem N et al. (2015) Sensory inputs control the integration of neurogliaform interneurons into cortical circuits. Nat Neurosci 18:393-401
Mayer, Christian; Jaglin, Xavier H; Cobbs, Lucy V et al. (2015) Clonally Related Forebrain Interneurons Disperse Broadly across Both Functional Areas and Structural Boundaries. Neuron 87:989-98

Showing the most recent 10 out of 23 publications