Dataset Information

Midbrain circuits that set locomotor speed and gait selection.

ABSTRACT: Locomotion is a fundamental motor function common to the animal kingdom. It is implemented episodically and adapted to behavioural needs, including exploration, which requires slow locomotion, and escape behaviour, which necessitates faster speeds. The control of these functions originates in brainstem structures, although the neuronal substrate(s) that support them have not yet been elucidated. Here we show in mice that speed and gait selection are controlled by glutamatergic excitatory neurons (GlutNs) segregated in two distinct midbrain nuclei: the cuneiform nucleus (CnF) and the pedunculopontine nucleus (PPN). GlutNs in both of these regions contribute to the control of slower, alternating-gait locomotion, whereas only GlutNs in the CnF are able to elicit high-speed, synchronous-gait locomotion. Additionally, both the activation dynamics and the input and output connectivity matrices of GlutNs in the PPN and the CnF support explorative and escape locomotion, respectively. Our results identify two regions in the midbrain that act in conjunction to select context-dependent locomotor behaviours.

SUBMITTER: Caggiano V

PROVIDER: S-EPMC5937258 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Midbrain circuits that set locomotor speed and gait selection.

Caggiano V V Leiras R R Goñi-Erro H H Masini D D Bellardita C C Bouvier J J Caldeira V V Fisone G G Kiehn O O

Nature 20180117 7689

Locomotion is a fundamental motor function common to the animal kingdom. It is implemented episodically and adapted to behavioural needs, including exploration, which requires slow locomotion, and escape behaviour, which necessitates faster speeds. The control of these functions originates in brainstem structures, although the neuronal substrate(s) that support them have not yet been elucidated. Here we show in mice that speed and gait selection are controlled by glutamatergic excitatory neurons ...[more]

PMID: 29342142

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Project description:Gait speed is a measure of general fitness. Changing from usual (UGS) to maximum (MGS) gait speed requires coordinated action of many body systems. Gait speed reserve (GSR) is defined as MGS-UGS. From a shortlist of 88 features across five categories including sociodemographic, cognitive, and physiological, we aimed to find and compare the sets of predictors that best describe UGS, MGS, and GSR. For this, we leveraged data from 3,925 adults aged 50+ from Wave 3 of The Irish Longitudinal Study on Ageing (TILDA). Features were selected by a histogram gradient boosting regression-based stepwise feature selection pipeline. Each model's feature importance and input-output relationships were explored using TreeExplainer from the Shapely Additive Explanations explainable machine learning package. The mean Radj2 (SD) from fivefold cross-validation on training data and the Radj2 score on test data were 0.38 (0.04) and 0.41 for UGS, 0.45 (0.04) and 0.46 for MGS, and 0.19 (0.02) and 0.21 for GSR. Each model selected features across all categories. Features common to all models were age, grip strength, chair stands time, mean motor reaction time, and height. Exclusive to UGS and MGS were educational attainment, fear of falling, Montreal cognitive assessment errors, and orthostatic intolerance. Exclusive to MGS and GSR were body mass index (BMI), and number of medications. No features were selected exclusively for UGS and GSR. Features unique to UGS were resting-state pulse interval, Center for Epidemiologic Studies Depression Scale (CESD) depression, sit-to-stand difference in diastolic blood pressure, and left visual acuity. Unique to MGS were standard deviation in sustained attention to response task times, resting-state heart rate, smoking status, total heartbeat power during paced breathing, and visual acuity. Unique to GSR were accuracy proportion in a sound-induced flash illusion test, Mini-mental State Examination errors, and number of cardiovascular conditions. No interactions were present in the GSR model. The four features that overall gave the most impactful interactions in the UGS and MGS models were age, chair stands time, grip strength, and BMI. These findings may help provide new insights into the multisystem predictors of gait speed and gait speed reserve in older adults and support a network physiology approach to their study.

Dataset Information

Midbrain circuits that set locomotor speed and gait selection.

Publications

Midbrain circuits that set locomotor speed and gait selection.

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