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Neural systems and circuits research team
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TEAM INTRODUCTION

presto minamimoto
Team Leader
Takafumi MINAMIMOTO Ph.D.

Our team seeks to understand how the brain works to regulate motivation, emotion and memory, and how the brain dysfunctions lead to symptoms in psychiatric disorders. We conduct unique researches using non-human primates with in vivo imaging techniques (PET, MRI) as well as chemogenetic techniques (DREADDs).

 

RESEARCH INTRODUCTION

Basic research on the neural and molecular mechanism of motivation,
emotion and memory using non-human primates.
 
1.Neural circuits for motiation, emotion and memory

A primary goal of our team is to understand the neural mechanisms underlying motivation, emotion and memory. To characterize the neural correlates of behavior at the network and single-neuron levels, we use fMRI/PET as well as electrophysiological recording. We also seek to identify the causal mechanisms using chemical or chemogenetic manipulations. Our research will facilitate our understanding the neural mechanism behind symptoms in neuropsychiatric disorders.

2.Imaging-guided chemogenetics

Genetic tools to chemically/optically control neuronal activity have been widely used to prove a causal link between specific neural circuits and behavior in small animals. To apply these techniques to non-human primates, however, post-mortem analysis has been required to evaluate the location and expression of constructs, making it expensive and logistically difficult. We have developed a non-invasive imaging method for visualization of DREADDs that improve the targeting and evaluation of chemogenetic constructs in monkeys. We are advancing this technique and trying to apply it to investigate behavior and therapeutic control.

Fig.2: PET-guided chemogenetic manipulation. 
PET imaging with DREADD-selective ligand [11C]CLZ, enabled us to evaluate the location and level of DREADD expression and allowed us to estimate the relationship between CNO dose and DREADD receptor occupancy in vivo, which is valuable information in subsequent behavioral experiments. This type of monitoring could be very valuable for application of gene-delivery techniques to long-term behavioral studies and clinical settings.
(Nagai et al. Nat Commun 2016). 
 
3. Imaging biomarkers for psychiatric and neurodegenerative disorders

Applying PET biomarkers in human studies to animal models, we attempt to understand the mechanism of symptoms. We are also aiming to establish new biomarkers originated from our findings of animal models studies.

brain image2

Fig. 3: PET imaging identified brain circuits involved in vocal tic generation. Vocal tics are inappropriate vocal expressions in Tourette syndrome that severely impact quality of life. Using the monkey model expressing vocal tic, we identified a brain network, involving anterior cingulate cortex (ACC, left) and amygdala (right), is activated
(McCairn, Nagai et al., Neuron 2016).

 
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