Evolution of optogenetic microdevices

Implementation of optogenetic techniques is a recent addition to the neuroscientists\u27 preclinical research arsenal, helping to expose the intricate connectivity of the brain and allowing for on-demand direct modulation of specific neural pathways. Developing an optogenetic system requires thorough investigation of the optogenetic technique and of previously fabricated devices, which this review accommodates. Many experiments utilize bench-top systems that are bulky, expensive, and necessitate tethering to the animal. However, these bench-top systems can make use of power-demanding technologies, such as concurrent electrical recording. Newer portable microdevices and implantable systems carried by freely moving animals are being fabricated that take advantage of wireless energy harvesting to power a system and allow for natural movements that are vital for behavioral testing and analysis. An investigation of the evolution of tethered, portable, and implantable optogenetic microdevices is presented, and an analysis of benefits and detriments of each system, including optical power output, device dimensions, electrode width, and weight is given. Opsins, light sources, and optical fiber coupling are also discussed to optimize device parameters and maximize efficiency from the light source to the fiber, respectively. These attributes are important considerations when designing and developing improved optogenetic microdevices

Portable closed-loop optogenetic stimulation device

This paper presents a closed-loop optogenetic stimulation device to achieve online modulation of neurons. The device is designed to be mountable on small rodents in pre-clinical settings. Considering the size of rodents and the need for portability, a single-piece self-contained device is developed which allows real-time photostimulation based on detected neuronal states. It consists of three components: a neural recorder, a control algorithm, and an optogenetic stimulator. The neural recorder which is realized by analogue circuitry measures the neural signal. The on-off control algorithm analyses the neural signal and controls the stimulation of the target neurons. The optogenetic stimulator performs sampling and digitization of the detected neural signal, runs the control algorithm, and manages the operation of the light source. The configurable neural recorder is capable of 64 dB amplification in the frequency range of 300 Hz to 6 KHz. The outcome of bench testing of the device is reported. The device is portable and headmountable which makes it suitable for use with small rodents in pre-clinical trials

Electrical resistance increases at the tissue-electrode interface as an early response to nucleus accumbens deep brain stimulation

The therapeutic actions of deep brain stimulation are not fully understood. The early inflammatory response of electrode implantation is associated with symptom relief without electrical stimulation, but is negated by anti-inflammatory drugs. Early excitotoxic necrosis and subsequent glial scarring modulate the conductivity of the tissue-electrode interface, which can provide some detail into the inflammatory response of individual patients. The feasibility of this was demonstrated by measuring resistance values across a bipolar electrode which was unilaterally implanted into the nucleus accumbens of a rat while receiving continuous deep brain stimulation with a portable back-mounted device using clinical parameters (130Hz, 200μ, 90μs) for 3 days. Daily resistance values rose significantly (

Wireless optogenetics: an exploration of portable microdevices for small animal photostimulation

Preclinical research in optogeneticneuromodulation in small laboratory animals allows far greater control of neural circuitry. This precision provides an enhanced opportunity for understanding the neural basis of behavior. However, behavioral neuroscience research is limited by conventional benchtop optogenetic systems. By necessity, the animal is tethered to the light source external to the testing environment. Portable optogeneticmicrodevices enhance the potential for valid behavioral testing in naturalistic conditions by eliminating tethering and enabling free and unrestricted movement. This paper reviews recent advances in the development of portable optogeneticmicrodevices supported by wireless power transfer. Light sources and fiber coupling are common problems in optogenetic systems and are addressed. Device designs and parameters are summarized, along with advances in component technology for energy storage and distribution that make these devices possible

Validation of a portable low-power deep brain stimulation device through anxiolytic effects in a laboratory rat model

Deep brain stimulation (DBS) devices deliver electrical pulses to neural tissue through an electrode. To study the mechanisms and therapeutic benefits of deep brain stimulation, murine preclinical research is necessary. However, conducting naturalistic long-term, uninterrupted animal behavioral experiments can be difficult with bench-top systems. The reduction of size, weight, power consumption, and cost of DBS devices can assist the progress of this research in animal studies. A low power, low weight, miniature DBS device is presented in this paper. This device consists of electronic hardware and software components including a low-power microcontroller, an adjustable current source, an n-channel metal-oxide-semiconductor field-effect transistor, a coin-cell battery, electrode wires and a software program to operate the device. Evaluation of the performance of the device in terms of battery lifetime and device functionality through bench and in vivo tests was conducted. The bench test revealed that this device can deliver continuous stimulation current pulses of strength 200μA, width 90μs, and frequency 130 Hz for over 22 days. The in vivo tests demonstrated that chronic stimulation of the nucleus accumbens (NAc) with this device significantly increased psychomotor activity, together with a dramatic reduction in anxiety-like behavior in the elevated zero-maze test

A review of brain insulin signaling in mood disorders: from biomarker to clinical target

Patients with mood disorders are at increased risk for metabolic dysfunction. Co-occurrence of the two conditions is typically associated with a more severe disease course and poorer treatment outcomes. The specific pathophysiological mechanisms underlying this bidirectional relationship between mood and metabolic dysfunction remains poorly understood. However, it is likely that impairment of metabolic processes within the brain play a critical role. The insulin signaling pathway mediates metabolic homeostasis and is important in the regulation of neurotrophic and synaptic plasticity processes, including those involved in neurodegenerative diseases like Alzheimer's. Thus, insulin signaling in the brain may serve to link metabolic function and mood. Central insulin signaling is mediated through locally secreted insulin and widespread insulin receptor expression. Here we review the preclinical and clinical data addressing the relationships between central insulin signaling, cellular metabolism, neurotrophic processes, and mood regulation, including key points of mechanistic overlap. These relationships have important implications for developing biomarker-based diagnostics and precision medicine approaches to treat severe mood disorders

Radio frequency energy harvesting from a feeding source in a passive deep brain stimulation device for murine preclinical research

This paper presents the development of an energy harvesting circuit for use with a head-mountable deep brain stimulation (DBS) device. It consists of a circular planar inverted-F antenna (PIFA) and a Schottky diode-based Cockcroft-Walton 4-voltage rectifier. The PIFA has the volume of π × 10(2) × 1.5 mm(3), resonance frequency of 915 MHz, and bandwidth of 16 MHz (909-925 MHz) at a return loss of -10 dB. The rectifier offers maximum efficiency of 78% for the input power of -5 dBm at a 5 kΩ load resistance. The developed rectenna operates efficiently at 915 MHz for the input power within -15 dBm to +5 dBm. For operating a DBS device, the DC voltage of 2 V is recorded from the rectenna terminal at a distance of 55 cm away from a 26.77 dBm transmitter in free space. An in-vitro test of the DBS device is presented