A Simple Stimulatory Device for Evoking Point-like Tactile Stimuli: A Searchlight for LFP to Spike Transitions

Summary

To elucidate the complex transition from Local Field Potentials (LFPs) to spikes a suitable stimulator for light mechanical peripheral stimuli was built. As an application, the spiking activities recorded from somatosensory cortex were analyzed by a multi-objective optimization strategy. The results demonstrated that the proposed stimulator was able to deliver tactile stimuli with millisecond and millimeter precisions.

Abstract

Current neurophysiological research has the aim to develop methodologies to investigate the signal route from neuron to neuron, namely in the transitions from spikes to Local Field Potentials (LFPs) and from LFPs to spikes.

LFPs have a complex dependence on spike activity and their relation is still poorly understood¹. The elucidation of these signal relations would be helpful both for clinical diagnostics (e.g. stimulation paradigms for Deep Brain Stimulation) and for a deeper comprehension of neural coding strategies in normal and pathological conditions (e.g. epilepsy, Parkinson disease, chronic pain). To this aim, one has to solve technical issues related to stimulation devices, stimulation paradigms and computational analyses. Therefore, a custom-made stimulation device was developed in order to deliver stimuli well regulated in space and time that does not incur in mechanical resonance. Subsequently, as an exemplification, a set of reliable LFP-spike relationships was extracted.

The performance of the device was investigated by extracellular recordings, jointly spikes and LFP responses to the applied stimuli, from the rat Primary Somatosensory cortex. Then, by means of a multi-objective optimization strategy, a predictive model for spike occurrence based on LFPs was estimated.

The application of this paradigm shows that the device is adequately suited to deliver high frequency tactile stimulation, outperforming common piezoelectric actuators. As a proof of the efficacy of the device, the following results were presented: 1) the timing and reliability of LFP responses well match the spike responses, 2) LFPs are sensitive to the stimulation history and capture not only the average response but also the trial-to-trial fluctuations in the spike activity and, finally, 3) by using the LFP signal it is possible to estimate a range of predictive models that capture different aspects of the spike activity.

Introduction

In the context of signal processing the impulse response provides a fundamental characterization of the behavior of a dynamical system.

Although the ideal impulse stimulus is practically not achievable, it is possible to obtain a reasonable approximation of it by using an actuator element that generates high frequency displacements. This type of light tactile-vibratory stimulation is known to target both deep skin (e.g. fast responding, fast adapting Pacinian corpuscles)² and superficial receptors (e.g. low-threshold slowly adapting Merkel discoid structures)².

Current stim....

Protocol

Ethical Statement

To study how sensory stimuli are represented by neuronal activity there is no alternative to the use of animals and the use of an in vivo approach. All the animals have been treated along the Italian and European Laws on animal treatment in Scientific Research (Italian Bioethical Committee, Law Decree on the Treatment of Animals in Research, 27 Jan 1992, No. 116). The National Research Council, where the experiments have been performed, adheres to the International Committee on Laboratory Animal Science (ICLAS) on behalf of the United Nations Educational, Scientific and Cultural Organizations (UNESCO), the Council fo....

Results

Tip excursion features

To characterize the dynamical properties of the proposed stimulating device, a series of experiments were set up. A specific device which consists of a gallium arsenide infrared emitting diode coupled with a silicon phototransistor was used to assess the tip displacement, the displacement duration and the possible displacement delays. By means of this optical interrupter switch we placed the stimulator tip on the edge of the emitting diode hole (height = 1 mm) and both the .......

Discussion

This work firstly presented a new, simple and low-cost device enabling to deliver fast and spatially point-like sensory stimuli. Then a randomized paired pulse stimulation protocol and a set of computational analyses were validated. The overall aim was to establish a framework for the estimation of LFP-spike relations in electrophysiological recordings during tactile stimulation.

The device, the protocol and the analytical approach have jointly contributed to the result, namely the first demon.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Microstepper	AB Transvertex (Stockholm, Sweden)		The microstepper used to pull down the electrode matrix
32-channel Cheetah System	Neuralynx (MT, USA)		The electrophysiological recording system
L293D h-bridge	RS Components (Cinisello Balsamo, Italy)		The bridge used to connect the microcontroller to the speaker
H21A3 Optical Interrupter Switch	Fairchild Semiconductor Corporation (San Jose, California)		The phototransistor used to estabilish the tip displacement
Arduino Uno	Arduino (Duemilanove, Italy)		The microcontroller used to deliver current pulse to the speaker
Microelectrode Matrices GB1	FHC
Isoflurane	Rhodia Organique Fine Ltd.		The anesthetic used to prepare animals
Stereotaxic apparatus	Narishighe (Tokyo, Japan)
Sprague-Dawley male rats	Charles River (Calco, LC, Italy)
Gallamine thriethiodide	Sigma-Aldrich		The compound used to curarize the animals
Cresyl violet	Sigma-Aldrich
Topical antiseptics (Betadine 10%)	Meda Pharma (Milanm Italy)
Heparine	Sigma-Aldrich
Formaldehyde	Carlo Erba Reagents (Pomigliano Milanese, Milan, Italy)