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Remote, brain region-specific control of choice behavior with ultrasonic waves.

ABSTRACT: The ability to modulate neural activity in specific brain circuits remotely and systematically could revolutionize studies of brain function and treatments of brain disorders. Sound waves of high frequencies (ultrasound) have shown promise in this respect, combining the ability to modulate neuronal activity with sharp spatial focus. Here, we show that the approach can have potent effects on choice behavior. Brief, low-intensity ultrasound pulses delivered noninvasively into specific brain regions of macaque monkeys influenced their decisions regarding which target to choose. The effects were substantial, leading to around a 2:1 bias in choices compared to the default balanced proportion. The effect presence and polarity was controlled by the specific target region. These results represent a critical step towards the ability to influence choice behavior noninvasively, enabling systematic investigations and treatments of brain circuits underlying disorders of choice.

SUBMITTER: Kubanek J

PROVIDER: S-EPMC7314556 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Remote, brain region-specific control of choice behavior with ultrasonic waves.

Kubanek Jan J Brown Julian J Ye Patrick P Pauly Kim Butts KB Moore Tirin T Newsome William W

Science advances 20200520 21

The ability to modulate neural activity in specific brain circuits remotely and systematically could revolutionize studies of brain function and treatments of brain disorders. Sound waves of high frequencies (ultrasound) have shown promise in this respect, combining the ability to modulate neuronal activity with sharp spatial focus. Here, we show that the approach can have potent effects on choice behavior. Brief, low-intensity ultrasound pulses delivered noninvasively into specific brain region ...[more]

PMID: 32671207

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Project description:Paraoxonase 2 (PON2) is an intracellular antioxidant enzyme shown to play an important role in mitigating oxidative stress in the brain. Oxidative stress is a common mechanism of toxicity for neurotoxicants and is increasingly implicated in the etiology of multiple neurological diseases. While PON2 deficiency increases oxidative stress in the brain in-vitro, little is known about its effects on behavior in-vivo and what global transcript changes occur from PON2 deficiency. We sought to characterize the effects of PON2 deficiency on behavior in mice, with an emphasis on locomotion, and evaluate transcriptional changes with RNA-Seq. Behavioral endpoints included home-cage behavior (Noldus PhenoTyper), motor coordination (Rotarod) and various gait metrics (Noldus CatWalk). Home-cage behavior analysis showed PON2 deficient mice had increased activity at night compared to wildtype controls and spent more time in the center of the cage, displaying a possible anxiolytic phenotype. PON2 deficient mice had significantly shorter latency to fall when tested on the rotarod, suggesting impaired motor coordination. Minimal gait alterations were observed, with decreased girdle support posture noted as the only significant change in gait with PON2 deficiency. Beyond one home-cage metric, no significant sex-based behavioral differences were found in this study. Finally, A subset of samples were utilized for RNA-Seq analysis, looking at three discrete brain regions: cerebral cortex, striatum, and cerebellum. Highly regional- and sex-specific changes in RNA expression were found when comparing PON2 deficient and wildtype mice, suggesting PON2 may play distinct regional roles in the brain in a sex-specific manner. Taken together, these findings demonstrates that PON2 deficiency significantly alters the brain on both a biochemical and phenotypic level, with a specific impact on motor function. These data have implications for future gene-environment toxicological studies and warrants further investigation of the role of PON2 in the brain.

Dataset Information

Remote, brain region-specific control of choice behavior with ultrasonic waves.

Publications

Remote, brain region-specific control of choice behavior with ultrasonic waves.

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