Gregory J. Gage

Selective Activation of Striatal Fast-Spiking Interneurons during Choice Execution

Basal ganglia circuits are essential for the organization and execution of voluntary actions. Within the striatum, fast-spiking interneurons (FSIs) are thought to tightly regulate the activity of medium-spiny projection neurons (MSNs) through feed-forward inhibition, yet few studies have investigated the functional contributions of FSIs in behaving animals. We recorded presumed MSNs and FSIs together with motor cortex and globus pallidus (GP) neurons, in rats performing a simple choice task. MSN activity was widely distributed across the task sequence, especially near reward receipt. By contrast, FSIs showed a coordinated pulse of increased activity as chosen actions were initiated, in conjunction with a sharp decrease in GP activity. Both MSNs and FSIs were direction selective, but neighboring MSNs and FSIs showed opposite selectivity. Our findings suggest that individual FSIs participate in local striatal information processing, but more global disinhibition of FSIs by GP is important for initiating chosen actions while suppressing unwanted alternatives.

Open Labware: 3-D Printing Your Own Lab Equipment

The introduction of affordable, consumer-oriented 3-D printers is a milestone in the current “maker movement,” which has been heralded as the next industrial revolution. Combined with free and open sharing of detailed design blueprints and accessible development tools, rapid prototypes of complex products can now be assembled in one’s own garage—a game-changer reminiscent of the early days of personal computing. At the same time, 3-D printing has also allowed the scientific and engineering community to build the “little things” that help a lab get up and running much faster and easier than ever before.

Wavelet Filtering before Spike Detection Preserves Waveform Shape and Enhances Single-Unit Discrimination

The isolation of single units in extracellular recordings involves filtering. Removing lower frequencies allows a constant threshold to be applied in order to identify and extract action potential events. However, standard methods such as Butterworth bandpass filtering perform this frequency excision at a cost of grossly distorting waveform shapes. Here, we apply wavelet decomposition and reconstruction as a filter for electrophysiology data and demonstrate its ability to better preserve spike shape. For the majority of cells, this approach also improves spike signal-to-noise ratio (SNR) and increases cluster discrimination. Additionally, the described technique is fast enough to be applied real-time.

The SpikerBox: a low cost, open-source bioamplifier for increasing public participation in neuroscience inquiry.

Although people are generally interested in how the brain functions, neuroscience education for the public is hampered by a lack of low cost and engaging teaching materials. To address this, we developed an open-source tool, the SpikerBox, which is appropriate for use in middle/high school educational programs and by amateurs. This device can be used in easy experiments in which students insert sewing pins into the leg of a cockroach, or other invertebrate, to amplify and listen to the electrical activity of neurons. With the cockroach leg preparation, students can hear and see (using a smartphone oscilloscope app we have developed) the dramatic changes in activity caused by touching the mechanosensitive barbs. Students can also experiment with other manipulations such as temperature, drugs, and microstimulation that affect the neural activity. We include teaching guides and other resources in the supplemental materials. These hands-on lessons with the SpikerBox have proven to be effective in teaching basic neuroscience.

Development of Closed-Loop Neural Interface Technology in a Rat Model: Combining Motor Cortex Operant Conditioning With Visual Cortex Microstimulation

Closed-loop neural interface technology that combines neural ensemble decoding with simultaneous electrical microstimulation feedback is hypothesized to improve deep brain stimulation techniques, neuromotor prosthetic applications, and epilepsy treatment. Here we describe our iterative results in a rat model of a sensory and motor neurophysiological feedback control system. Three rats were chronically implanted with microelectrode arrays in both the motor and visual cortices. The rats were subsequently trained over a period of weeks to modulate their motor cortex ensemble unit activity upon delivery of intra-cortical microstimulation (ICMS) of the visual cortex in order to receive a food reward. Rats were given continuous feedback via visual cortex ICMS during the response periods that was representative of the motor cortex ensemble dynamics. Analysis revealed that the feedback provided the animals with indicators of the behavioral trials. At the hardware level, this preparation provides a tractable test model for improving the technology of closed-loop neural devices.

Local dynamics of gap-junction-coupled interneuron networks

Interneurons coupled by both electrical gap-junctions (GJs) and chemical GABAergic synapses are major components of forebrain networks. However, their contributions to the generation of specific activity patterns, and their overall contributions to network function, remain poorly understood. Here we demonstrate, using computational methods, that the topological properties of interneuron networks can elicit a wide range of activity dynamics, and either prevent or permit local pattern formation. We systematically varied the topology of GJ and inhibitory chemical synapses within simulated networks, by changing connection types from local to random, and changing the total number of connections. As previously observed we found that randomly coupled GJs lead to globally synchronous activity. In contrast, we found that local GJ connectivity may govern the formation of highly spatially heterogeneous activity states. These states are inherently temporally unstable when the input is uniformly random, but can rapidly stabilize when the network detects correlations or asymmetries in the inputs. We show a correspondence between this feature of network activity and experimental observations of transient stabilization of striatal fast-spiking interneurons (FSIs), in electrophysiological recordings from rats performing a simple decision-making task. We suggest that local GJ coupling enables an active search-and-select function of striatal FSIs, which contributes to the overall role of cortical-basal ganglia circuits in decision-making.

Surgical Implantation of Chronic Neural Electrodes for Recording Single Unit Activity and Electrocorticographic Signals

The success of long-term electrophysiological recordings often depends on the quality of the implantation surgery. Here we provide useful information for surgeons who are learning the process of implanting electrode systems. We demonstrate the implantation procedure of both a penetrating and a surface electrode. The surgical process is described from start to finish, including detailed descriptions of each step throughout the procedure. It should also be noted that this video guide is focused towards procedures conducted in rodent models and other small animal models. Modifications of the described procedures are feasible for other animal models.

Correction: Open Labware: 3-D Printing Your Own Lab Equipment

[This corrects the article DOI: 10.1371/journal.pbio.1002086.].

Information Capacity of Brain Machine Interfaces

Brain machine interfaces (BMIs) are emerging as an important research area in clinical therapy. A large range of potential BMI control signals can be found in the brain. In increasing order of volume of brain tissue being sampled, these signal includes recordings of electric discharges from multi unit activity (MUA), summed population activity of thousands of neurons via local field potentials (LFPs), and electrical activity recorded from either the surface of the brain via electrocorticograms (ECoGs) or the surface of the scalp via electroencephalograms (EEGs). While each of these signals have been studied separately, it has been difficult to compare the potential that each signal has for general prosthetic control across studies. Information theory has been proposed as an abstract measurement to bridge this gap, however the maximum information rates of any experiment is limited by the parameters defined by that experiment (e.g. inter-trial interval length, number of targets). Here we propose a different measure of information, which we call information capacity, which measures the maximum possible information rate that a signal can provide. An advantage of measuring information capacity is that it can readily be compared between different signals and different tasks. We show how to calculate information capacity making linear Gaussian assumptions, and we discuss more general possibilities. We present a case study involving a rat BMI task involving either MUA or LFP signals

Portable conduction velocity experiments using earthworms for the college and high school neuroscience teaching laboratory.

The earthworm is ideal for studying action potential conduction velocity in a classroom setting, as its simple linear anatomy allows easy axon length measurements and the worms sparse coding allows single action potentials to be easily identified. The earthworm has two giant fiber systems (lateral and medial) with different conduction velocities that can be easily measured by manipulating electrode placement and the tactile stimulus. Here, we present a portable and robust experimental setup that allows students to perform conduction velocity measurements within a 30-min to 1-h laboratory session. Our improvement over this well-known preparation is the combination of behaviorally relevant tactile stimuli (avoiding electrical stimulation) with the invention of minimal, low-cost, and portable equipment. We tested these experiments during workshops in both a high school and college classroom environment and found positive learning outcomes when we compared pre- and posttests taken by the students.