DEPARTMENT OF INTEGRATIVE PHYSIOLOGY

Outline

Department of Integrative Physiology has two Laboratories, Laboratory of Sensori-Motor Integration (Chair: Ryusuke Kakigi) and Laboratory of System Neurophysiology (Chair: Atsushi Nambu). Although there are many departments named Integrative Physiology in Japan at present, Department of Integrative Physiology at NIPS was founded as the first one in Japan. Laboratory of Sensori-Motor Integration is investigating human brain functions using various methods of neuroimaging such as electroencephalography, magnetoencephalography, functional magnetic resonance imaging, near-infrared spectroscopy and transcranial magnetic stimulation. Laboratory of System Neurophysiology is investigating brain functions in animals, mainly monkey. In particular, they focus on the function of basal ganglia and cerebral cortex and their connection, and aim at clarifying pathophysiology and finding therapeutic methods of various diseases in humans by animal studies.

Division of Sensori-Motor Integration

We investigate human brain functions non-invasively mainly using magnetoencephalography(MEG) and electroencephalography (EEG), but recently we have also used functional magnetic resonance imaging (fMRI), transcranial magnetic stimulation (TMS) and near infrared spectroscopy (NIRS). Integrative studies using various methods are necessary to understand the advantages and disadvantages of each method. The following investigations are in progress at present.

(1) Sensory system: By recording brain responses to visual, auditory, somatosensory or pain stimuli, the organization of sensory processing in the human brain is being investigated. In particular, our interest is focused on the underlying mechanisms of pain and itch perception.

(2) Even-related brain responses: Using various psychophysical tasks or paradigms, we are investigating cognitive processing of the brain (higher brain functions). In particular, our interest is focused on the underlying mechanisms of face perception, inhibition processing using Go-NoGo paradigm, and masking phenomenon using repetitive stimuli，and brain response to mismatch stimulation.

(3) Application of brain research to society (Social brain): Recently we focused on the development of brain function in infants and children. EEG and NIRS are useful in this study, since these methods can be applied to infants and children who can not hold their heads still for a long time.

306-channel helmet-shaped MEG recording system (ELEKTA-Neuromag, Finland)

Newly developed stimulating electrodes inducing itch feeling (upper figure). MEG (yellow and blue circle) and fMRI (red regions) following itch stimulation indicate that secondary somatosensory cortex (SII), insula and precuneus in bilateral hemisphere are commonly activated by both methods (lower figure).

Staff

Living animals, including human beings, obtain many pieces of information from the external and internal environments, integrate them to make a decision for appropriate behavioral activity, and finally take action based on self-intension. The brainareas, such as the cerebral cortex, basal ganglia and cerebellum, play a major role in the voluntary movements. On the other hand, malfunctions of these structures result in movement disorders, such as Parkinson's disease. The major goal of our research programs is to elucidate the mechanisms underlying higher motor functions and the pathophysiology of movement disorders. To explore such intricate brain functions, we employ a wide range of neurophysiological and neuroanatomical techniques.

The current topics under study are as follows: 1) Elucidation of information flows through the neuronal networks by electrophysiological and anatomical methods; 2) Understanding the mechanism how the brain controls voluntary movements by electrophysiological recordings of neuronal activity from animals performing motor tasks, combined with local injection of neuronal blockers or optogenetics; 3) Elucidation of the pathophysiology of movement disorders by recording neuronal activity from animal models; 4) Understanding the pathophysiology of movement disorders by analyzing neuronal activity recorded in human patients during stereotaxic surgery.

Schematic model explaining functions of the basal ganglia and pathophysiology of movement disorders. The hyperdirect, direct and indirect pathways control the activity of the thalamus (Th), and relaease only the selected motor program at the appropriate timing (left). In hypokinetic disorders such as Parkinson's disease (center), reduced disinhibition in the thalamus through the direct pathway results in akinesia. On the other hand, reduced activity in the GPi/SNr induces excessive disinhibition on the thalamus and results in involuntary movements in hyperkinetic disorders such as dystonia (right).

Wriggle Mouse Sagami, one of the models of movement disorders.

Staff

The goal of the Division of Computational Neuroscience is to clarify roles of nonlinear dynamics in neural systems for realization of brain functions. In particular, we are elucidating how a diversity of phenomena in nonlinear dynamical systems, e.g., bistability, entrainment, chaos, and transitive dynamics, are involved in various cognitive functions such as memory and attention. We are also combining mathematics and physiology, e.g., by trying conductance injection (dynamic clamp) and developing a new method to analyze in vivo data, and exploring the way to make biologically sound models and testable predictions.

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(A) Neocortical pyramidal cells have extensively branched dendrites, and recent physiological studies have shown that integration of synaptic inputs in each dendritic branch may entail nonlinearity (Left, schematic diagram). Analyzing a mathematical model of microcircuit incorporating a reduced form of such branch-specific nonlinear integration, it was suggested that the dendritic nonlinearity may contribute to the stability of the circuit against noisy background inputs (Right, there exists a low-activity stable state when the S/N ratio is small: Morita et al., Neural Comput, 2007). (B) Inferior olive (IO) neurons show intriguing spatio-temporal dynamics with rhythmic and synchronized spiking. We proposed a gap junction-coupled network composed of simple conductance-based model neurons and optimized its parameter values so that the network reproduce the patterns of spike activity recorded from IO neurons in rats (Left ). Analyses of the model imply that both intrinsic bistability of each neuron (Right ) and the gap junction coupling play key roles in the generation of the spatio-temporal dynamics (Katori et al., IJBC, 2009).

Staff