Actomyosin, a complex of actin filaments and myosin motor proteins, is responsible for force generation during muscle contraction. To resolve the individual mechanical events of force generation by actomyosin, we have developed a new instrument with which we can capture and directly manipulate individual myosin subfragment-1 molecules using a scanning probe. Single subfragment-1 molecules can be visualized by using a fluorescent label. The data that we obtain using this technique are consistent with myosin moving along an actin filament with single mechanical steps of approximately 5.3 nanometres; groups of two to five rapid steps in succession often produce displacements of 11 to 30 nanometres. This multiple stepping is produced by a single myosin head during just one biochemical cycle of ATP hydrolysis.

Synaptic inputs on dendrites are nonlinearly converted to action potential outputs, yet the spatiotemporal patterns of dendritic activation remain to be elucidated at single-synapse resolution. In rodents, we optically imaged synaptic activities from hundreds of dendritic spines in hippocampal and neocortical pyramidal neurons ex vivo and in vivo. Adjacent spines were frequently synchronized in spontaneously active networks, thereby forming dendritic foci that received locally convergent inputs from presynaptic cell assemblies. This precise subcellular geometry manifested itself during N-methyl-D-aspartate receptor-dependent circuit remodeling. Thus, clustered synaptic plasticity is innately programmed to compartmentalize correlated inputs along dendrites and may reify nonlinear synaptic integration.

A persistent change in neuronal activity after brief stimuli is a common feature of many neuronal microcircuits. This persistent activity can be sustained by ongoing reverberant network activity or by the intrinsic biophysical properties of individual cells. Here we demonstrate that rat and guinea pig cerebellar Purkinje cells in vivo show bistability of membrane potential and spike output on the time scale of seconds. The transition between membrane potential states can be bidirectionally triggered by the same brief current pulses. We also show that sensory activation of the climbing fiber input can switch Purkinje cells between the two states. The intrinsic nature of Purkinje cell bistability and its control by sensory input can be explained by a simple biophysical model. Purkinje cell bistability may have a key role in the short-term processing and storage of sensory information in the cerebellar cortex.