Biology subjects

Yanagihara, D.

Publications and source records attributed to Yanagihara, D..

3 recordsLinked to original sources

bioRxiv2025

A neural circuit targeting technique for investigating functional input-output organization in the nervous system

Neurons communicate information across circuits and the function of cells in these circuits is determined by both the afferent inputs they receive and the efferent outputs they send to other brain regions1,2. To study the activity and function of specific neuronal populations, transneuronal anterograde3 and retrograde4-6 viral approaches have been employed to define neural circuit elements by inputs or outputs, respectively. However, what is missing is a way to study the function of neurons based on both their inputs and outputs. Applying a combination of multiple recombinases and transneuronal anterograde/retrograde viruses, we developed a technique called input-output Projection-based INtersectional Circuit-tagging Enabled by Recombinases (PINCER) to target specific neuronal cell types and investigate functional input-output organization in neural circuits. We show the logic and application of this technique with in vivo calcium imaging and optogenetic approaches to reveal the distinct functions and neural dynamics of connectivity defined neuronal populations in the amygdala for emotional processing. Specifically, PINCER allowed the parsing of valence and salience functions of the amygdala to reveal an input-output cell type selectively mediating aversive memory formation. This technique allows neuroscientists to identify novel subclasses of cells based on their combinatorial input-output anatomical connectivity, providing a tool for fine dissection of the functional properties of neural circuits.

neuroscience↗

bioRxiv2024

A novel behavioral paradigm using mice to study predictive postural control

Postural control circuitry performs the essential function of maintaining balance and body position in response to perturbations that are either self-generated (e.g. reaching to pick up an object) or externally delivered (e.g. being pushed by another person). Human studies have shown that anticipation of predictable postural disturbances can modulate such responses. This indicates that postural control could involve higher-level neural structures associated with predictive functions, rather than being purely reactive. However, the underlying neural circuitry remains largely unknown. To enable studies of predictive postural control circuits, we developed a novel experimental paradigm for mice. In this paradigm, modeled after human studies, a dynamic platform generated reproducible translational perturbations. While mice stood bipedally atop a perch to receive water rewards, they experienced backward translations that were either unpredictable or preceded by an auditory cue. To validate the paradigm, we investigated the effect of the auditory cue on postural responses to perturbations across multiple days in three mice. These preliminary results serve to validate a new postural control experimental paradigm, opening the door to the types of neural recordings and circuit manipulations that are currently possible in mice. Significance StatementThe ability to anticipate disturbances and adjust ones posture accordingly--known as "predictive postural control"--is crucial for preventing falls and for advancing robotics. While human balance is often assessed via floor perturbations, rodent studies typically use rotarod tests. Here, we developed a postural perturbation task for freely moving mice, modeled after those used in human studies. Using a dynamic platform, we delivered reproducible perturbations with or without preceding auditory cues and quantified how the auditory cue affects postural responses to perturbations. Our work provides validation of a new postural control experimental paradigm, which opens the door to the types of neural population recordings and circuit manipulation that are currently possible in mice.

neuroscience↗

bioRxiv2022

Simulation of the effect of the randomness of climbing fiber input on the relationship between motor learning and Focal Task-Specific Dystonia

Focal Task-Specific Dystonia (FTSD) is an intractable neurological disorder with no clear prevention or treatment that affects more than 1% of classical musicians and threatens the active lives of experts due to its task-specific tremor symptoms. In the present study, we focused on the motor learning function of the cerebellum, which has not been the focus of much attention in the past. We numerically simulated the firing of cerebellar Purkinje cells and cerebellar nuclei during eyeblink conditioning as a typical example of cerebellar-related timing motor learning, with the aim to find the principle of the pathogenesis of FTSD at the level of individual neurons. The results showed the sustained firing of cerebellar nuclei after the learning condition in which the climbing fiber input to Purkinje cells was continued randomly. Therefore, the present study claims a suggestive factor regarding the neural mechanism of the cerebellum in the motor learning-induced task-specific tremor, which is a symptom of FTSD. We also proposed a motor learning paradigm, "undesirable motor learning," in which the motor goal is too advanced to be achieved by repetitions alone and converges to a different result than the desired.

neuroscience↗