Synaptic Protein Networks, Genetic Risk, and Spine Loss in Schizophrenia

Project: Research project

Project Details

Description

Dr. Kozorovitskiy, Assistant Professor of Neurobiology at Northwestern University will oversee the work pertaining to AIM 2. To test the effects of top-candidate Sz Phos alterations on Al layer 3 spine density, size, formation, and stability. We will assist in the design of vectors to manipulate phosophorylation of candidate hits from proteomic analyses, provide any necessary viral vector plasmids for cloning new constructs, carry out the injection of AAVs to deliver viral vectors to mouse primary auditory cortex, and carry out all experiments proposed in AIM 2B, using dual-laser 2-photon uncaging and imaging systems, integrated with whole cell electrophysiology. Mice sparsely expressing one of several candidate phosphomimics or phosphonulls, fluorophore controls, or native gene controls will be used to evaluate de novo spinogenesis and synaptogenesis, as well as single synapse function in layer 3 pyramidal neurons of primary auditory cortex, a brain area where synaptic structure and circuit function in altered in Schizophrenia, in conjunction with auditory processing impairments.
Northwestern University site will work closely with University of Pittsburg to design and carry out experiments, perform quality controls, analyze the data, and synthesize across the aims of the overall project. We will use best practices in data sharing and management. Interactions across the sites will be facilitated by weekly to bi-weekly phone or video conferences during the period covered by the scope of work (years 3-5 of the grant), with less frequent but consistent interactions from grant initiation date.
StatusActive
Effective start/end date5/1/214/30/24

Funding

  • University of Pittsburgh (AWD00000863 (133093-1)//5R01MH118497-03)
  • National Institute of Mental Health (AWD00000863 (133093-1)//5R01MH118497-03)

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