The human brain is a wonderfully enigmatic organ, helping to juggle multiple tasks efficiently to help us get through a long day! This characteristic, called executive function, puts primates like us at the peak of evolution. The prospect of losing the spectacular flow of neural information in our brains due to an accident or illness is therefore disconcerting. In the event of such an unfortunate event, to restore the brain to its previous functioning state with all of its functionality – to restart it, so to speak – would require a better understanding of the specific neural pathways involved in our day-to-day activities that rely on working memory and decision making – two important executive functions.
To achieve this goal, a group of researchers from the National Institutes for Quantum and Radiological Science and Technology (QST), Japan, have worked hard to design a technique they call “imaging-guided chemogenetic synaptic silence” to decipher specific neural pathways. involved. in high level executive functions. In a pioneering study published in Scientists progress, researchers now report having successfully delineated specific neural pathways involved in working memory and decision-making using this technique.
The group, led by eminent researcher Dr. Takafumi Minamimoto of the Department of Functional Brain Imaging, QST, focused on studying the dorsolateral part of the prefrontal cortex (dlPFC) in the monkey brain, to apply their new technique and further identify neurons pathways of interest. It is interesting to note this choice, not only because it is the brain region partly responsible for the control of executive functions, but also because this specialized region is only present in primates.
It is important to note that the role of dlPFC is also supported by regions of the brain such as the dorsal caudate (dCD) and the lateral mediodorsal thalamus (MDl). This complex association is explained in more detail by Dr. Kei Oyama, who is the first author of the study, as follows: “The primate prefrontal cortex (PFC), in particular its dorsolateral part (dlPFC), is well known for serve as a center for higher-order executive functions; it is uniquely developed in primates and underpins their distinctive cognitive abilities. These functions, however, do not rely solely on dlPFC neurons, but also on their cooperative interactions with subcortical structures, including the dorsal caudate nucleus (dCD) and lateral mediodorsal thalamus (MD1). “
Next, the researchers wanted to understand who-does-what for working memory and decision-making. Since dlPFC, MDI, and dCD neurons are connected, they selectively silenced specific neural synapses to disrupt the flow of information and perform only dlPFC-dCD and dlPFC-MD1 projections, i.e. unilaterally (involving only one side brain), or bilaterally (involving both sides). To achieve this, they made dlPFC neurons express designer receptors exclusively activated by designer drugs (DREADD). Additionally, the monkeys involved in the study were analyzed for changes in behavior, to understand the effect of chemogenetic silence.
Interestingly, the researchers observed that the silence of bilateral dlPFC-MDl projections in monkeys, but not their dlPFC-dCD projections, caused working memory problems related to their environment. On the contrary, silencing their unilateral dlPFC-dCD projections, but not their unilateral dlPFC-MDl projections, altered their preference in decision-making. These results reveal that the two higher brain functions, working memory and decision-making, essential to our daily life, are controlled by different neural pathways connecting specific areas of the brain.
Overall, this study lays the groundwork for further explorations of the intricacies of the complex primate brain. In this regard, Dr. Oyama explains the potential clinical and research applications of these findings: “Many psychiatric disorders, including depression, are believed to be associated with disruptions in the transmission of neural information through neural circuits between patients. specific regions of the brain. Our findings are expected to deepen our understanding of mental disorders and lead to the discovery of treatments and cures. The successful development of a new technique in our study will serve as a key technology for the next generation of researchers to study the brain functions of primates, which will contribute to large areas of life by dramatically deepening our understanding of the mechanism of higher brain functions. . “
The world will indeed anxiously await future mysteries to unfold as explorations take seekers deeper into the labyrinthine labyrinth of the mind.
“Chemogenetic dissection of the pre-fronto-subcortical pathways of primates for working memory and decision-making”
Kei Oyama, Yukiko Hori, Yuji Nagai, Naohisa Miyakawa, Koki Mimura, Toshiyuki Hirabayashi, Ken-ichi Inoue, Tetsuya Suhara, Masahiko Takada, Makoto Higuchi and Takafumi Minamimoto
Scientists progress: June 23, 2021, DOI: https: /
About the National Institutes of Quantum and Radiological Sciences and Technologies:
The National Institutes for Quantum and Radiological Science and Technology (QST) was established in April 2016 to promote quantum science and technology in a holistic and integrated manner. QST’s mission is to raise the level of quantum and radiological sciences and technologies through its commitment to research and development in quantum sciences and technologies, the effect of radiation on humans, radiological emergency medicine and medical use of radiation. To ensure that research and development produces significant academic, social and economic impacts, and to maximize the benefits of global innovation, QST strives to establish leading research and development platforms and explore new areas.
About Dr Kei Oyama from the National Institutes for Quantum and Radiological Science and Technology, Japan:
Dr Kei Oyama is a renowned researcher in the Department of Functional Brain Imaging. Specifically, Dr. Oyama is an active member of the Neural Systems and Circuits research group. He is an expert in different facets of behavioral and cognitive neuroscience, such as learning and memory, behavior analyzes, neuropharmacology, electrophysiology etc. Its expertise is reinforced by around twenty publications in these fields, in reputable journals.
This study was funded by grant numbers MEXT / JSPS KAKENHI JP18K15353 and JP21K07268, JP17H02219, JP19H05467, JP15H05917 and JP18H04037, JP18H05018 and JP19K07811; Strategic grant from the president of the QST (creative research); AMED grant numbers JP20dm0307007, JP20dm0307021, JP18dm0207003 and JP20dm0107146; JST PRESTO grant number JPMJPR1683; cooperative research program at PRI, Kyoto University; and National Bio-Resource Project “Japanese Monkeys” from MEXT, Japan
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