The aim of this project is to create a system for studying cultured neural networks that will provide a unique new ability for observing how each cell is connected to the others and how that connectivity changes. The cultured neurons will be in "cages" that are plastic structures which allow process outgrowth but maintain the cell body in close proximity to a recording and stimulating electrode. By stimulating each neuron and recording the responses of all the others, the connectivity of the network will be revealed. The system will have 64 cages in an 8 x 8 array, with 64 dissociated neurons placed in cages using an optical tweezers. The capability to study such networks in detail at the single cell level will be far beyond any that now exists. Recording and stimulation do not damage the neurons, so the connectivity can be observed over a period of weeks, as the network develops. Very sophisticated electronic amplifiers and stimulators on custom large scale integrated circuits will be used, which will provide at low cost the capability of studying multiple caged arrays simultaneously, while they are in an incubator. The studies will provide an opportunity to observe normal network development in detail that has never been possible. In addition, the effects on networks of imposed simulation will be revealed, on time scales of hours to weeks. Pharmacological effects on connectivity will also be observable. Lastly, because they are in cages, cell types can be mixed and placed in known locations, so that type-specific interactions between them as they form networks will be observable. A most interesting example will be to observe the interaction of embryonic-stem-cell derived neurons with networks of normal neurons. As a proof of concept at the end of this study, such experiments will be begun. They will indicate the potential for stem-cell-neuron integration with normal cells in transplants, and also will provide opportunities for studying how to promote that integration.

Public Health Relevance

The capability for studying cultured networks that this project provides will provide important new data on network development, plasticity, and pharmacological responses. This will be relevant to medical applications that ameliorate neurological problems using chronic stimulation and drugs. In addition, the experiments with embryonic stem cell neurons will provide a unique opportunity to study the integration of neural transplants with normal cells, which is very relevant to possible medical applications of transplants.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21NS075114-01A1
Application #
8289108
Study Section
Neurotechnology Study Section (NT)
Program Officer
Ludwig, Kip A
Project Start
2012-02-01
Project End
2013-12-31
Budget Start
2012-02-01
Budget End
2012-12-31
Support Year
1
Fiscal Year
2012
Total Cost
$235,120
Indirect Cost
$85,120
Name
California Institute of Technology
Department
None
Type
Schools of Arts and Sciences
DUNS #
009584210
City
Pasadena
State
CA
Country
United States
Zip Code
91125