We cannot read a book, listen to music, taste our meals, enjoy sport, or do anything that is essential for living, unless our brains can sense the world around us.

The neural mechanisms for sensory processing have been investigated for the past one hundred years. We are now aware of the mechanisms for detection of sensory signals by sensory neurons. However, examining the mechanisms the brain uses to integrate sensory inputs remains a challenge.

Our goal is to reveal how neuronal circuits work as a system to process sensory inputs, and how this processing is modulated by a specific environment or by the mental state or the condition of the body. The answers to these questions would reveal how an animal displays adaptive behavior in response to a given situation that changes every moment, or even develops intelligent behavior to cope with a difficult situation. To study these problems in our laboratory, we are utilizing two invertebrate animals, the fly and the cephalopod.

The invertebrate system

The invertebrate has evolved its own nervous system. Unlike that of the vertebrate, the invertebrate neuron is monopolar and the axon is not surrounded by a myelin sheath. The neurons do not form the layered structures observed in the mammalian neocortex, but instead an outer layer of cell bodies surrounds the neuropil. In addition, the invertebrate has developed unique lobed structures within its brain.

Although the features of neurons and the structure of the brain are quite different between invertebrates and vertebrates, the sensory system occasionally shows astonishing similarities between them. For example, the olfactory systems of vertebrates and invertebrates share general rules: olfactory sensory neurons selectively express a single olfactory receptor gene; the primary olfactory center forms spherical structures called glomeruli; olfactory sensory neurons expressing the same olfactory receptor protein all converge into one of the glomeruli. Such similarities have fascinated neurobiologists who would like to investigate brain function in a relatively simple animal model, because the vertebrate brain is too large and complex to study. The invertebrate system has also attracted many researchers because of its ability to adapt to its environment and perform unique behaviors with a relatively small, simple brain.

To dissect the sensory system, we are currently studying two invertebrate species. One is the fruit fly Drosophila melanogaster, a model animal to which we can easily apply genetic methods. Drosophila has a relatively small brain with which we can analyze brain function at the level of a “neuronal” circuit. We can now manipulate the activity of a specific population of neurons and record the neural response with conventional electrophysiological methods or newly developed imaging methods. These techniques have helped us to analyze the function of any neurons involved in sensory processing.

The other animal model that we utilize is the cephalopod, which is a unique intelligent species. It can change the color and texture of its skin instantly as camouflage and can elegantly move arms that lack any joints. The octopus shows the ability to learn from another’s behavior by observation and can use tools, whereas the squid displays social behavior. Although its structure is completely different from that of vertebrates, the cephalopod brain can exhibit comparable intelligence. Brain function in the cephalopod has been studied intensely through surgical injury, and the giant axon in the squid has been studied in the past to demonstrate the nerve-conduction properties of the axon. The time has now come to investigate how the brain lobes process sensory information. We started the cephalopod project by studying the nervous system of a pygmy squid, Idiosepius paradoxus as a model. This species is the smallest squid and can be raised and maintained in still seawater in a laboratory. We first made a 3D atlas of the squid brain and began recording the brain's neural responses.

Fly projects since 1999

The fruit fly, Drosophila melanogaster, is a relatively simple model with abundant genetic tools. We have identified about 200 GAL4 enhancer trap strains each of which can induce gene expression in various types of olfactory neurons. Using these strains, we have revealed the connectivity between olfactory brain areas. The function of most of these neurons, however, has not yet been examined. Recording the odor responses from such neurons by expressing calcium indicator proteins within GAL4 lines, targeting electrodes to cells expressing fluorescent protein, or manipulating the neural transmission or membrane potential of these neurons by expressing effector genes will enable us to investigate their function. We can also analyze the synaptic connectivity between specific neurons using electron microscopy. The primary goal of this project is to understand how each olfactory neuron processes sensory inputs by communicating with neighboring neurons, and how the brain enables us to recognize the origin of an odor.

We are also interested in the mechanisms for modifying olfactory processing according to the condition of the body. It has been reported that the odor response is greater in a starved fly than a fed fly, and this is mediated by neuropeptides. We have also found that starvation and the mating experience can change the sensory response threshold. We are studying the mechanism for regulating this threshold.

Cephalopod projects since 2014

We have recently started a project to study the visual system related to camouflage. The squid can change its body color according to the circumstances, though it is regarded as color-blind. The color change can even be partially restricted, for example to half of the body. To understand the neural mechanism of camouflage, we intend to examine color processing and the correlations between retinotopic and somatotopic maps in the brain. We are planning how to investigate the neural origins of intelligent behavior using this animal.

In addition, we are exploring the challenge of subculturing this species. Since the adults lay many eggs even in an aquarium environment, it would be possible to subculture this species if we can find an efficient way to raise hatchlings for a few weeks.