Seizures initiate in zones of relative hyperexcitation in a zebrafish epilepsy model.

Seizures are thought to arise from an imbalance of excitatory and inhibitory neuronal activity. While most classical studies suggest excessive excitatory neural activity plays a generative role, some recent findings challenge this view and instead argue that excessive activity in inhibitory neurons initiates seizures. We investigated this question of imbalance in a zebrafish seizure model with two-photon imaging of excitatory and inhibitory neuronal activity throughout the brain using a nuclear-localized calcium sensor. We found that seizures consistently initiated in circumscribed zones of the midbrain before propagating to other brain regions. Excitatory neurons were both more prevalent and more likely to be recruited than inhibitory neurons in initiation as compared with propagation zones. These findings support a mechanistic picture whereby seizures initiate in a region of hyperexcitation, then propagate more broadly once inhibitory restraint in the surround is overcome.

Drosophila uses a tripod gait across all walking speeds, and the geometry of the tripod is important for speed control.

Changes in walking speed are characterized by changes in both the animal's gait and the mechanics of its interaction with the ground. Here we study these changes in walking Drosophila. We measured the fly's center of mass movement with high spatial resolution and the position of its footprints. Flies predominantly employ a modified tripod gait that only changes marginally with speed. The mechanics of a tripod gait can be approximated with a simple model - angular and radial spring-loaded inverted pendulum (ARSLIP) - which is characterized by two springs of an effective leg that become stiffer as the speed increases. Surprisingly, the change in the stiffness of the spring is mediated by the change in tripod shape rather than a change in stiffness of individual legs. The effect of tripod shape on mechanics can also explain the large variation in kinematics among insects, and ARSLIP can model these variations.

Spring-loaded inverted pendulum goes through two contraction-extension cycles during the single-support phase of walking.

Despite the overall complexity of legged locomotion, the motion of the center of mass (COM) itself is relatively simple, and can be qualitatively described by simple mechanical models. In particular, walking can be qualitatively modeled by a simple model in which each leg is described by a spring-loaded inverted pendulum (SLIP). However, SLIP has many limitations and is unlikely to serve as a quantitative model. As a first step to obtaining a quantitative model for walking, we explored the ability of SLIP to model the single-support phase of walking, and found that SLIP has two limitations. First, it predicts larger horizontal ground reaction forces (GRFs) than empirically observed. A new model - angular and radial spring-loaded inverted pendulum (ARSLIP) - can overcome this deficit. Second, although the leg spring (surprisingly) goes through contraction-extension-contraction-extensions (CECEs) during the single-support phase of walking and can produce the characteristic M-shaped vertical GRFs, modeling the single-support phase requires active elements. Despite these limitations, SLIP as a model provides important insights. It shows that the CECE cycling lengthens the stance duration allowing the COM to travel passively for longer, and decreases the velocity redirection between the beginning and end of a step.