Automated electrophysiological analysis of neural circuitry using a novel nano electrode array for intracellular recording of membrane potential

Summary
Nervous systems process information by integrating the electrical activity of neurons in complex
networks The alterations in the flow of electrical activity through neuronal networks of the brain
play a causal role in the pathogenesis and or the appearance of symptoms of neurodegenerative
and psychiatric diseases A fundamental goal of BRAIN Initiative is therefore to elucidate how the
brainandapos s neural circuits are structurally and functionally connected a prerequisite for hypotheses
guided developments of more effective pharmacological treatments of these diseases
Unfortunately this goal remains elusive at present largely due to the lack of technology to perform
scalable recording and manipulation of neural activity with high S N ratio at single cell level over
long period of time and under physiological conditions The classic method of electrophysiology
requires physical contact and electrical coupling between the recording electrodes and the cells
under investigation which presents different challenges regarding the two primary forms of
technologies currently available Intracellular recording methods by sharp electrode or patch
clamping constrains the measurement to one cell at a time and limits the recording time to several
minutes due to the invasive nature of this approach Extracellular recording with parallel planar
electrode array lacks single cell resolution and fails to detect subthreshold synaptic potentials
The absence of adequate environmental control for both methods further reduces the
physiological relevance of the results
The novel electrophysiology platform proposed in this STTR application aims to provide a
powerful solution that bridges the long standing gap between high quality non scalable
intracellular electrophysiology and low quality scalable extracellular electrophysiology so to
enable for the first time simultaneous noninvasive measurement of intracellular membrane
potential from many neurons under optimal physiological conditions Central to this platform is
the seamless integration of two innovative approaches parallel nano fabricated biocompatible
electrodes and sensitive environmentally robust electronics We also plan to validate the
complete system for analyzing neural network using in vitro culture of cortical neurons
In summary the ability to monitor the activities of larger neuronal networks simultaneously and
non invasively is a necessary prerequisite to understanding how neuronal networks function at
the systems level Our breakthrough technology is well positioned to provide a significantly
improved cellular electrophysiology system for large scale recording and manipulation of neural
activity with an immediate and positive impact on BRAIN Initiative s central objective to
understand the dynamic activity of neural circuits This system with further development can
support recording from even larger number of neurons of different types and for other
applications such as neurotoxicity evaluation for drug development Public Health Relevance
Large scale recording and manipulation of neural activity remains one of the greatest challenges for the
understanding of how the brainandapos s neural circuits are structurally and functionally connected This study aims to
develop a full integrated electrophysiology system based on a novel nano electrode technology for parallel
recording and manipulation of neural activity with high S N ratio at single cell level over long period of time
and under physiological conditions