Abstract

We describe an optical technique for label-free detection of the action potential in cultured mammalian neurons. Induced morphological changes due to action potential propagation in neurons are optically interrogated with a phase sensitive interferometric technique. Optical recordings composed of signal pulses mirror the electrical spike train activity of individual neurons in a network. The optical pulses are transient nanoscale oscillatory changes in the optical path length of varying peak magnitude and temporal width. Exogenous application of glutamate to cortical neuronal cultures produced coincident increase in the electrical and optical activity; both were blocked by application of a Na-channel blocker, Tetrodotoxin. The observed transient change in optical path length in a single optical pulse is primarily due to physical fluctuations of the neuronal cell membrane mediated by a yet unknown electromechanical transduction phenomenon. Our analysis suggests a traveling surface wave in the neuronal cell membrane is responsible for the measured optical signal pulses.

Highlights

  • The essential role of neurons is to integrate excitatory and inhibitory synaptic inputs at the level of the neuron soma and dendrites, and transmit this electrochemical information by triggering an action potential(s) (AP) that is propagated along axons to the nerve terminals where the neurotransmitter release activates the second-order neurons [1, 2]

  • Rat cortical neurons were maintained under standard neuronal culture for a period of 14-17 days, over which time they formed an interconnected network of synaptic connection capable of generating self-sustained spontaneous electrical activity

  • Recording experiments were started by first measuring baseline interference signal from a blank region of the device (Fig. 2(B)) to establish the optical path difference (OPD) noise floor

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Summary

Introduction

The essential role of neurons is to integrate excitatory and inhibitory synaptic inputs at the level of the neuron soma and dendrites, and transmit this electrochemical information by triggering an action potential(s) (AP) that is propagated along axons to the nerve terminals where the neurotransmitter release activates the second-order neurons [1, 2] Neuronal relays such as these represent the fundamental units of neuronal networks from the simplest invertebrates to the complex neural circuitry of the human brain. Electrophysiological techniques require placement of an electrode in direct contact or close proximity to neurons, presenting inherent technical limitations [8, 9]. These limitations can be a significant hurdle in studies that require long term and high throughput recordings in a network of neurons. Recent developments in multi-electrode array (MEA) electronics platforms have improved throughput and minimized the invasiveness, but remain limited by electrode density and inflexibility of the arrays [10,11,12,13]

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