No abstract

The climbing fiber input to the cerebellar cortex is thought to provide instructive signals that drive the induction of motor skill learning. We found that optogenetic activation of Purkinje cells, the sole output neurons of the cerebellar cortex, can also drive motor learning in mice. This dual control over the induction of learning by climbing fibers and Purkinje cells can expand the learning capacity of motor circuits.

Developing biomaterial constructs that closely mimic the natural tissue microenvironment with its complex chemical and physical cues is essential for improving the function and reliability of implantable devices, especially those that require direct neural-electrical interfaces. Here we demonstrate that free-standing vertically aligned carbon nanofiber (VACNF) arrays can be used as a multifunctional 3-D brush-like nanoengineered matrix that interpenetrates the neuronal network of PC12 cells. We found that PC12 neuron cells cultured on VACNF substrates can form extended neural network upon proper chemical and biochemical modifications. The soft 3-D VACNF architecture provides a new platform to fine-tune the topographical, mechanical, chemical, and electrical cues at subcellular nanoscale. This new biomaterial platform can be used for both fundamental studies of material-cell interactions and the development of chronically stable implantable neural devices. Micropatterned multiplex VACNF arrays can be selectively controlled by electrical and electrochemical methods to provide localized stimulation with extraordinary spatiotemporal resolution. Further development of this technology may potentially result in a highly multiplex closed-loop system with multifunctions for neuromodulation and neuroprostheses.

The rate and temporal pattern of neural spiking each have the potential to influence computation. In the cerebellum, it has been hypothesized that the irregularity of interspike intervals in Purkinje cells affects their ability to transmit information to downstream neurons. Accordingly, during oculomotor behavior in mice and rhesus monkeys, mean irregularity of Purkinje cell spiking varied with mean eye velocity. However, moment-to-moment variations revealed a tight correlation between eye velocity and spike rate, with no additional information conveyed by spike irregularity. Moreover, when spike rate and irregularity were independently controlled using optogenetic stimulation, the eye movements elicited were well-described by a linear population rate code with 3–5 ms temporal precision. Biophysical and random-walk models identified biologically realistic parameter ranges that determine whether spike irregularity influences responses downstream. The results demonstrate cerebellar control of movements through a remarkably rapid rate code, with no evidence for an additional contribution of spike irregularity.