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Functional Evaluation of Biological Neurotoxins in Networked Cultures of Stem Cell-derived Central Nervous System Neurons
Published on: February 5, 2015
Improving bioassay sensitivity for neurotoxins detection using volterra based third order nonlinear analysis.
Ghassan I Gholmieh1, Spiros H Courellis, D Fluster
1Children Hospital Los Angeles, Division of Neurology, 4650 Sunset Blvd, MS 82, Los Angeles, CA 90027, USA. ggholmieh@chla.usc.edu
Summary
A new third-order Volterra model enhances a biosensor for detecting nervous system compounds. This improved method offers greater sensitivity and discriminatory power for classifying unknown chemicals affecting neural plasticity.
Area of Science:
- Neuroscience
- Pharmacology
- Biomedical Engineering
Background:
- A biosensor utilizing short-term plasticity (STP) analysis in the CA1 hippocampal region was developed for chemical compound screening.
- The existing method employed first-order Volterra kernels and second-order Volterra model Laguerre coefficients for classification.
- This biosensor demonstrated success in correctly classifying novel chemical compounds.
Purpose of the Study:
- To explore the benefits of incorporating a third-order Volterra model into the existing biosensor analytical method.
- To assess if a third-order model can improve the sensitivity and classification capabilities for neuroactive compounds.
Main Methods:
- Analysis of evoked population spikes in the CA1 hippocampal region in response to random impulse train stimuli.
- Application of first and second-order Volterra models and their Laguerre coefficients for signal analysis.
- Re-analysis of data using a third-order Volterra model to evaluate its performance.
Main Results:
- A known NMDA channel blocker (DAP5) showed minimal changes in the second-order Volterra kernel and its coefficients.
- The same compound (DAP5) exhibited discernible alterations in the third-order Volterra kernel and associated Laguerre coefficients.
- The third-order model revealed changes not apparent with the second-order model.
Conclusions:
- The third-order Volterra based model shows significant potential to enhance the sensitivity of the neuroactive compound screening bioassay.
- Incorporating a third-order model may improve the discriminatory power of the biosensor for classifying chemical compounds affecting the nervous system.
- This advanced analytical approach could lead to more effective detection and classification of novel neurochemical agents.
