A04 Alteration of brain dynamics as underlying mechanisms of hyper-adaptability in neurotransmitter disorders
Research Outline
Kaoru TAKAKUSAKI
Our daily activities consist of continuous and parallel multi-tasking, which requires integration of executive functions (attention, prediction, working memory, etc.) and motor functions. This cognitive-motor linkage is impaired by neurodegenerative disorders as well as aging in which dysfunctions of neurotransmitter systems co-exist with neural degeneration. Here we hypothesize that the “hyper-adaptation” compensates for the functional decline in aging and neurodegenerative diseases, which involve abnormality in neurotransmitters such as dopamine (DA) and acetylcholine (ACh). Specifically, the present research project is designed to test the hypothesis that the alteration of neural dynamics following abnormal DA or ACh neurotransmissions may lead to the change of “rule of the conduct” as an underlying mechanism of “hyper-adaptation”.
To test this hypothesis, we will conduct both clinical (Hanakawa et al.) and animal (Takakusaki et al.) studies. In the clinical study, we will focus on decline of the midbrain DA system in aging and Parkinson’s disease. We will use brain imaging and brain stimulation techniques to know the causal relationship between the changes in DA-dependent neural dynamics and executive functions involved in action selection. We aim to identify “parameters of altered neural dynamics associated with aging”. In the animal experimentation, we will focus on the ACh system, which is deteriorated in Alzheimer-type dementia, in addition to the DA system. In multi-tasks of posture control during walking and forelimb reaching in the cat, we will try to identify the alteration of dynamics in the cortical and subcortical neural network before and after damages to subcortical ACh and DA systems, which will be induced by molecular genetics procedures.
We will collaborate with Model Research Group (B04) to elucidate the specific functions of each neurotransmitter, which affects the alteration of action rules that lead to hyper-adaptation. Our findings will be also shared with the A01 and B01 research groups, which will contribute to “elucidation of motivation of behavior (A01)” and “construction of mathematical models for posture control (B01)”
Members
| Principal investigator | Kaoru TAKAKUSAKI | Professor, Asahikawa Medical University |
| Funded co-investigator | Takashi HANAKAWA | Professor, Graduate School of Medicine, Kyoto University |
| Co-investigators | Tomohiro NOGUCHI | Lecturer, Asahikawa Medical University |
| Mirai TAKAHASHI | Visiting Assistant Professor, Asahikawa Medical University | |
| Syusei HUKUYAMA | Assistant Professor, Asahikawa Medical University | |
| Toshikatsu OKUMURA | Professor, Asahikawa Medical University | |
| Tsukasa NOZU | Professor, Asahikawa Medical University | |
| Seiji MATSUMOTO | Professor, Asahikawa Medical University | |
| Hitoshi SASAJIMA | Lecturer, Asahikawa Medical University | |
| Sadaharu MIYAZONO | Lecturer, Asahikawa Medical University | |
| Tatsuya UMEDA | Associate Professor, Kyoto University | |
| Yoshifumi MORI | Assistant Professor, Kyoto University | |
| Kenji YOSHINAGA | Assistant Professor, Kyoto University | |
| Tatsuhiro Nakamura | Project Researcher, Kyoto University | |
| Yuki OI | Graduate Student, Kyoto University | |
| Masakazu HIROSE | Graduate Student, Kyoto University | |
| Toshi NAKAJIMA | Associate Professor, University of Toyama | |
| Hiroki TOGO | Postdoctoral fellow, NCNP | |
| Toma MATSUSHIMA | Undergraduate Student, Tokyo University of Agriculture and Technology (Research Student, NCNP) |