Chemogenetic dissection of the primate prefronto-subcortical pathways for working memory and decision-making

「何を買うんだっけ」と「どれにしよう」を処理する2つの脳回路を明らかに --霊長類の生体脳で神経経路を可視化・操作する技術で解明、高次脳機能の理解へ大きく前進--. 京都大学プレスリリース. 2021-06-24.The primate prefrontal cortex (PFC) is situated at the core of higher brain functions via neural circuits such as those linking the caudate nucleus and mediodorsal thalamus. However, the distinctive roles of these prefronto-subcortical pathways remain elusive. Combining in vivo neuronal projection mapping with chemogenetic synaptic silencing, we reversibly dissected key pathways from dorsolateral part of the PFC (dlPFC) to the dorsal caudate (dCD) and lateral mediodorsal thalamus (MDl) individually in single monkeys. We found that silencing the bilateral dlPFC-MDl projections, but not the dlPFC-dCD projections, impaired performance in a spatial working memory task. Conversely, silencing the unilateral dlPFC-dCD projection, but not the unilateral dlPFC-MDl projection, altered preference in a decision-making task. These results revealed dissociable roles of the prefronto-subcortical pathways in working memory and decision-making, representing the technical advantage of imaging-guided pathway-selective chemogenetic manipulation for dissecting neural circuits underlying cognitive functions in primates

Chemogenetic attenuation of cortical seizures in nonhuman primates

「てんかん」の発生を時間的・空間的にピンポイントで抑える画期的な治療法を開発 --世界で初めてサルでの有効性を実証、臨床応用に向け大きく前進--. 京都大学プレスリリース. 2023-03-01.Epilepsy is a disorder in which abnormal neuronal hyperexcitation causes several types of seizures. Because pharmacological and surgical treatments occasionally interfere with normal brain function, a more focused and on-demand approach is desirable. Here we examined the efficacy of a chemogenetic tool—designer receptors exclusively activated by designer drugs (DREADDs)—for treating focal seizure in a nonhuman primate model. Acute infusion of the GABAA receptor antagonist bicuculline into the forelimb region of unilateral primary motor cortex caused paroxysmal discharges with twitching and stiffening of the contralateral arm, followed by recurrent cortical discharges with hemi- and whole-body clonic seizures in two male macaque monkeys. Expression of an inhibitory DREADD (hM4Di) throughout the seizure focus, and subsequent on-demand administration of a DREADD-selective agonist, rapidly suppressed the wide-spread seizures. These results demonstrate the efficacy of DREADDs for attenuating cortical seizure in a nonhuman primate model

Novel method of extracting motion from natural movies

tBackground: The visual system in primates can be segregated into motion and shape pathways. Interactionoccurs at multiple stages along these pathways. Processing of shape-from-motion and biological motionis considered to be a higher-order integration process involving motion and shape information. However,relatively limited types of stimuli have been used in previous studies on these integration processes.New method: We propose a new algorithm to extract object motion information from natural movies andto move random dots in accordance with the information. The object motion information is extracted byestimating the dynamics of local normal vectors of the image intensity projected onto the x-y plane ofthe movie.Results: An electrophysiological experiment on two adult common marmoset monkeys (Callithrix jacchus)showed that the natural and random dot movies generated with this new algorithm yielded comparableneural responses in the middle temporal visual area.Comparison with existing methods: In principle, this algorithm provided random dot motion stimuli con-taining shape information for arbitrary natural movies. This new method is expected to expand theneurophysiological and psychophysical experimental protocols to elucidate the integration processingof motion and shape information in biological systems.Conclusions: The novel algorithm proposed here was effective in extracting object motion informationfrom natural movies and provided new motion stimuli to investigate higher-order motion informationprocessing.© 2017 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license(http://creativecommons.org/licenses/by/4.0/)