Joshua H. Siegle

Selective optical drive of thalamic reticular nucleus generates thalamic bursts and cortical spindles

The thalamic reticular nucleus (TRN) is hypothesized to regulate neocortical rhythms and behavioral states. Using optogenetics and multi-electrode recording in behaving mice, we found that brief selective drive of TRN switched the thalamocortical firing mode from tonic to bursting and generated state-dependent neocortical spindles. These findings provide causal support for the involvement of the TRN in state regulation in vivo and introduce a new model for addressing the role of this structure in behavior.

Enhancement of encoding and retrieval functions through theta phase-specific manipulation of hippocampus

Assessing the behavioral relevance of the hippocampal theta rhythm has proven difficult, due to a shortage of experiments that selectively manipulate phase-specific information processing. Using closed-loop stimulation, we triggered inhibition of dorsal CA1 at specific phases of the endogenous theta rhythm in freely behaving mice. This intervention enhanced performance on a spatial navigation task that requires the encoding and retrieval of information related to reward location on every trial. In agreement with prior models of hippocampal function, the behavioral effects depended on both the phase of theta and the task segment at which we stimulated. Stimulation in the encoding segment enhanced performance when inhibition was triggered by the peak of theta. Conversely, stimulation in the retrieval segment enhanced performance when inhibition was triggered by the trough of theta. These results suggest that processes related to the encoding and retrieval of task-relevant information are preferentially active at distinct phases of theta. DOI: http://dx.doi.org/10.7554/eLife.03061.001

Measurement of instantaneous perceived self-motion using continuous pointing

In order to optimally characterize full-body self-motion perception during passive translations, changes in perceived location, velocity, and acceleration must be quantified in real time and with high spatial resolution. Past methods have failed to effectively measure these critical variables. Here, we introduce continuous pointing as a novel method with several advantages over previous methods. Participants point continuously to the mentally updated location of a previously viewed target during passive, full-body movement. High-precision motion-capture data of arm angle provide a measure of a participant’s perceived location and, in turn, perceived velocity at every moment during a motion trajectory. In two experiments, linear movements were presented in the absence of vision by passively translating participants with a robotic wheelchair or an anthropomorphic robotic arm (MPI Motion Simulator). The movement profiles included constant-velocity trajectories, two successive movement intervals separated by a brief pause, and reversed-motion trajectories. Results indicate a steady decay in perceived velocity during constant-velocity travel and an attenuated response to mid-trial accelerations.

Chronically implanted hyperdrive for cortical recording and optogenetic control in behaving mice

Neural stimulation technology has undergone a revolutionary advance with the introduction of light sensitive ion channels and pumps into genetically identified subsets of cells. To exploit this technology, it is necessary to incorporate optical elements into traditional electrophysiology devices. Here we describe the design, construction and use of a “hyperdrive” capable of simultaneous electrical recordings and optical stimulation. The device consists of multiple microdrives for moving electrodes independently and a stationary fiber for delivering light to the tissue surrounding the electrodes. We present data demonstrating the effectiveness of inhibitory recruitment via optical stimulation and its interaction with physiological and behavioral states, determined by electrophysiological recording and videographic monitoring.

Design and fabrication of ultralight weight, adjustable multi-electrode probes for electrophysiological recordings in mice.

The number of physiological investigations in the mouse, mus musculus, has experienced a recent surge, paralleling the growth in methods of genetic targeting for microcircuit dissection and disease modeling. The introduction of optogenetics, for example, has allowed for bidirectional manipulation of genetically-identified neurons, at an unprecedented temporal resolution. To capitalize on these tools and gain insight into dynamic interactions among brain microcircuits, it is essential that one has the ability to record from ensembles of neurons deep within the brain of this small rodent, in both head-fixed and freely behaving preparations. To record from deep structures and distinct cell layers requires a preparation that allows precise advancement of electrodes towards desired brain regions. To record neural ensembles, it is necessary that each electrode be independently movable, allowing the experimenter to resolve individual cells while leaving neighboring electrodes undisturbed. To do both in a freely behaving mouse requires an electrode drive that is lightweight, resilient, and highly customizable for targeting specific brain structures. A technique for designing and fabricating miniature, ultralight weight, microdrive electrode arrays that are individually customizable and easily assembled from commercially available parts is presented. These devices are easily scalable and can be customized to the structure being targeted; it has been used successfully to record from thalamic and cortical regions in a freely behaving animal during natural behavior.

Cortical Circuits: Finding Balance in the Brain

Maintaining the right balance between excitation and inhibition is crucial to healthy brain function. A recent study has used optogenetics to show how quickly and effectively inhibition clamps down a novel burst of excitation in the neocortex.

High-precision capture of perceived velocity during passive translations

▪ During passive transport, participants point continuously to a previously viewed target (white ball mounted at shoulder height) ▪ Intuitive task to perform; less likely to be biased by cognitive influences ▪ Participants instructed not to attend to their own velocity, only to the perceived location of the external target ▪ Following analysis, we recover perceived velocity in absolute, real-world units (m/s) ▪ Requires the assumptions that the initial target location is accurately perceived, and that all pointing errors can be attributed to errors in perceived self-motion (Loomis & Philbeck, in press) ▪ Continuous pointing has been previously used for: ▫ Distance perception (Loomis et al., 1992) ▫ Perception of rotation (Ivanenko et al., 1997; Siegler et al., 1999) ▪ Never used as an explicit measure of instantaneous translational velocity ▪ Same method used in Campos et al. (2008) to show that the characteristic pointing behavior seen during actual translation is not present when subjects imagine themselves moving