Keio University Human BiologyMicrobiome-Quantum
Research Center (Bio2Q)

Message to Young Readers
While the drive to conduct research that benefits others iscrucial, I believe that delving into what you find mysterious
or intriguing will ultimately lead to more fundamental
discoveries. I encourage young people to prioritize thepursuit of interesting endeavors. Curiosity, in my opinion, isthe driving force behind all meaningful discoveries.
For example, if you have a close relative suffering from adisease, it is natural to be inclined to research a cure forthat specific disease. However, I believe it's more beneficial
to conduct research that delves deeper into the essence ofthe disease. This is especially true for high school students,
who should strive to have a broad perspective on things. Inaddition, mastering basic academic skills is crucial, so I
encourage you to study diligently. In particular, proficiency
in math and English will serve you well throughout yourresearch endeavors.
I urge you to pursue intriguing endeavors. Curiosity is thedriving force behind significant discoveries.

I encourage you to prioritize exploring
things that you find interesting ormysterious. This curiosity is the driving
force behind fundamental discoveries.

What is Bio2Q?
Bio2Q is a world-class research center at Keio University. It aims
to use quantum computing and AI to analyze the interaction
between Human Biology and Microbiome, revealing uncharted
territories of the human body and developing new treatments forintractable diseases.

Keio University Shinanomachi Campus
35 Shinanomachi, Shinjuku-ku, Tokyo
160-8582, Japan

Email: sc-wpi-staff@adst.keio.ac.jp
Web: www.bio2q.keio.ac.jp
Tel: 03-6709-8106 (Weekdays 8:30 AM - 5:00 PM)

ProfessorMichisuke YuzakiSpecial Advisor to Director of Bio2Q / Neuroregulation TeamISSUE 03

Bio2Q

Bio2Q ResearchersMAR. 2024

It is the first private university to be selected for the World PremierInternational Research Center Initiative (WPI) program promotedby the Ministry of Education, Culture, Sports, Science andTechnology (MEXT).

Please tell us about your research.

Neurons

Presynaptic Terminal

My aim is to understand brain processes related to thoughts andmemories—particularly focusing on why memory deteriorates in
conditions like dementia, the cause of auditory hallucinations, andattention deficits in certain mental disorders—from theperspective of brain function.
Conditions often viewed as purely physical, such as stomach
ulcers and immune disorders, are linked to mental health. This
insight during high school spurred my pursuit of a medical career,
recognizing the importance of the mental aspects in physicalillnesses. In university, I delved into psychosomatic medicine andpsychiatry but soon realized my understanding of the brain wassuperficial. This led me to basic neuroscience, aiming to grasp
brain mechanisms from the ground up.
The heart and liver function through the assembly of theirrespective cells, but brain cells, or neurons, require a network ofconnections, or synapses, to process information, think, andremember. Understanding synapse formation, modification, andelimination at the molecular level is crucial. This knowledge will
help us understand neuropsychiatric and developmental
disorders' pathophysiology and develop new treatment strategies
for synaptic impairments.

Synapticformation
molecules

Postsynaptic Terminal

Between neurons, there are molecules that
act like adhesives. These molecules, known
as synaptic formation molecules, play acrucial role. Understanding the functions ofthese synaptic formation molecules may
enable the recovery of lost synapses inconditions such as psychiatric disorders anddevelopmental disabilities, potentially leading
to effective treatments.

01

Synapses

Neurons extend their processes like arms
and legs to connect with other neurons.
The points where they connect are calledsynapses.

Our research addresses two key memory mechanisms in the brain.
First, we examine how the wiring of neural circuits adapts tochanges in neural activity. We've discovered that the complement
family* of molecules, typically associated with immunity, is a key
regulator of synapse formation and removal in the brain.
Second, we study how memory is stored at existing synapses
without changing the wiring. For example, studying all night for an
exam doesn't mean that new synapses will be formed by the nextday. Rather, existing synapses strengthen and become more
efficient at transmitting information, which is a form of memory.
This process is faster and requires fewer resources than rewiring.

Memory formation is not just a result of studying for anexamination. Activities like exercise or musical practice can embed
memories in the cerebellum, while persistent pain or drug
addiction form distinct memory types. Our research aims todetermine whether different memories, stored in various regionsof the brain, stem from new synapse formation or from alterationsin the efficiency of pre-existing synapses.

Are there any collaborative projects with other labs at
Bio2Q?

Postsynaptic Terminal

Unlike a computer whose wiring is fixed once manufactured, thebrain's synaptic connections evolve with neural activity. With
humans having around 20,000 genes but nearly 1,000 trillion
synapses, it's clear that genes alone don't dictate the complex
organization of neuronal networks. Instead, neural circuits arerefined through pruning and tuning synapses in response tolearning.

In both computers and neural circuits, information is transmitted
via electrical signals. However, in the brain, these signals are halted
at synapses. A presynaptic neuron releases glutamate upon
sending an electrical signa. This glutamate binds to receptors on
the postsynaptic neuron, resuming the signal. Therefore, boosting
the number of glutamate receptors on the postsynaptic neuron
enhances information transmission, even if glutamate release isconstant. On the other hand, decreasing these receptors lowers
transmission efficiency. This modification in postsynaptic
glutamate receptors, either increasing or decreasing, is key toforming memories and can last from several hours to several days.
In the **hippocampus, for example, the number of glutamate
receptors at a single synapse can double from 100 to 200 during
learning.

Presynaptic Terminal

If we want to understand how the brain
functions, it is crucial to comprehend
the workings of synapses.”
What is the difference between a brain and acomputer?

How are memories stored at existing synapses
without rewiring?

02

Presynaptic TerminalYes, we're collaborating with Dr. Kenya Honda's lab on the study ofgut bacteria and their metabolites. We know that gut bacteria
produce metabolites that affect brain function, but how changes inthese metabolites are detected and communicated to the brain isstill unclear. Our goal is to identify the neural circuits involved in
the brain-gut axis. Understanding the molecules that drive
synapse formation in these circuits could enable us to alter thebrain's connections from the gut, offering new avenues for disease
treatment.
My interest has always been in the interplay between mind andbody, a fascination that began in high school. By unraveling how
the gut and its bacteria influence synapses, I aim to further explore
this relationship.

Postsynaptic Terminal

Glutamate

Glutamate Receptor

When short-to-medium-term memories areformed (Fig. 02), the number of glutamate
receptors at the synaptic terminals increases.
As a result, even if the same amount ofglutamate is released from the presynaptic
terminal, the response at the postsynaptic
terminal becomes more significant.

*Complement family: Complement is a protein that plays a role in the innate immune system,
serving as the first step in the recognition and elimination of foreign bodies. The group of proteinsthat share a motif with complement is called the complement family.
**Hippocampus: A region of the brain responsible for storing and organizing new episodic
memories.