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Feasibility Study

Developing of the opticalrecording technique

of neural activity in the brain of having monkey

Toshio Iijima

■Object

The elaborate mechanisms of the brain are achieved by some peculiar biological phenomena such as a self organization (assembly) of neuronal circuit and a neuronal plasticity.For the further study to elucidate the brain functions,it is essential to develop new equipment and their application techniques with which we can obtain quite new information in quality about the brain functions.

In this study,we are developing optical recording devices and techniques which can be applicable for the recording of brain activities of a behaving monkey.This developments enable us to visualize in real-time the progress of neuronal excitation over a wide area of the cerebral cortex.This should largely extend our knowledge about functions of the brain.

■Results in Fiscal Year

(1) Background and significance of this study

In an information processing of the brain,in general, several different functional domains distributed separately in the brain work co-operatively to complete the processing.Thus,multiple sites of the brain are activated almost at the same time in each information processing.Traditionally,the brain functions have been studied with a conventional electrophysiological method with an electrode,as a unit recording or a field potential recording.However the method is obviously not suitable for the study to understand the mutual relationships between each functional domains and even for the study of the functional architecture of each domains.On the other hand,PET (Positron Emission Tomography)or fMRI (functional Magnetic Resonance Imaging), although each of which has an capability of tracting neural activities localized three dimensionally in the space of a whole brain,does not detect neural exciation but detects metabolic changes associated with the neural activities.

Information of the spatio-temporal distribution of neuronal activity(exciation) in the brain during the signal processing is very significant in the elucidation of the higher functions of the brain,because they are crucial for the examinations of hypotheses of cerebral information processin,such as a functional column,a sparse coding of information,a parallel information processing and a hierarchical information processing.Recently we have developed an optical recording system of neural activity with a high spatio-temporal resolution (references 1-4).If we could realize the application of this recording method to a behaving animal,it should be a very powerful tool for the analysis of the higher functions of the brain.

(2)Technical problem to be overcome

In the fiscal year of 1995,we tried to find what is the most important issue to be solved to realize the application of optical method to a behaving animal,through the real experiments with monkeys.As a result,the points were summarized as follows;

A)How to maintain the cortical surface after removal of the skull and the dura matter.

B)How to minimize the damage of cortical surface by a voltage-sensitive dye staining.

C)How to reduce the noise associated with heart beats and breathing.

D)How to reduce the noise associated with voluntary movements.

In the experiments we also tried to find the solution of each items,and obtained tentative conclusions.The issues A) to C) may be solved by the improvements of the recording chamber to be fixed to the skull surrounding the recording site of the brain.The issue D) may be solved by the direct fixation of an optical device,which is now under fabrication,to the skull.By the direct fixation,the relative position of an objective cortical surface and an image sensor will be maintained and result in the reduction of the noise.

(3) Optical recording obtained in the preliminary experiments

During the preliminary experiments,although they are designed to clarify the issues in the application of optical recording of brain actvity,we succeeded in recording the neuronal responses in the primary somatosensory cortex (SI) with an optical method using a voltage-sensitive dye. The recordings were performed in monkeys under weak anesthesia. In ten milliseconds after an application of mechanical stimulus to the tip of one of fingers,an optical signal reflecting neuronal excitations came to appear in a part of the area 3b of SI,then the actvities spread to the area 1 successively. Through this type of experiments,a part of the functional architecture of monkey SI cortex was revealed(reference 5).

In this study we are aiming to establish the optical recording method applicable to an awake monkey during voluntary movement,and thereby analyze the higher brain functions.This preliminary results seem to imply that our trial is very promising and realistic.


Fig.1

Experimental set up for recording neuroral responses of monkey SI cortex with an optical recording method.

Fig.2

Optical signal change in the SI cortex of monkey induced by a finger tip stimulation (lower traces) and a real-time imaging of the response (upper panel).


Reference

1) Toshio Iijima;Optical imaging neural excitations.,Saibou vol.27,25-29(1995)

2)Toshio Iijima;Architecture of neurons and representation of information.,in Brain,Mind and Computer (Maruzen Co.Ltd)59-75(1995)

3） T. Iijima, M.P. Witter, M. Ichikawa, T. Tominaga, R. Kajiwara, G. Matsumoto; Entorhinol-Hippocampal Interctions Revealed by Real-Time Imaging. Science, 272, 1176-1179, 1996

4） M.E. Barish, M. Ichikawa, T. Tominaga, G. Matsumoto, T. Iijima; Enhanced fast synaptic transmission and a delayed depolarization induced by transient current blockade in rat hippocampal slice as studied by optical recording., J. Neuroscience, in press (1996)

5） T. Iijima, K. Kurata, H. Komatsu, M. Ichikawa, I. Takashima; Digit representations in the primary somatosensory cortex of monkeys as revealed by a real-time optical recording. J. Neurophysiol. in press (1996)