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Long Term Amperometric Recordings in the Brain Extracellular Fluid of Freely Moving Immunocompromised NOD SCID Mice.

ABSTRACT: We describe the in vivo characterization of microamperometric sensors for the real-time monitoring of nitric oxide (NO) and oxygen (O₂) in the striatum of immunocompromised NOD SCID mice. The latter strain has been utilized routinely in the establishment of humanized models of disease e.g., Parkinson's disease. NOD SCID mice were implanted with highly sensitive and selective NO and O₂ sensors that have been previously characterized both in vitro and in freely moving rats. Animals were systemically administered compounds that perturbed the amperometric current and confirmed sensor performance. Furthermore, the stability of the amperometric current was investigated and 24 h recordings examined. Saline injections caused transient changes in both currents that were not significant from baseline. l-NAME caused significant decreases in NO (p < 0.05) and O₂ (p < 0.001) currents compared to saline. l-Arginine produced a significant increase (p < 0.001) in NO current, and chloral hydrate and Diamox (acetazolamide) caused significant increases in O₂ signal (p < 0.01) compared against saline. The stability of both currents were confirmed over an eight-day period and analysis of 24-h recordings identified diurnal variations in both signals. These findings confirm the efficacy of the amperometric sensors to perform continuous and reliable recordings in immunocompromised mice.

SUBMITTER: Reid CH

PROVIDER: S-EPMC5335951 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Extracellular recordings of electrical activity in freely moving rats are fundamental to understand brain function in health and disease. Such recordings require a small-size, lightweight device that includes movable electrodes (microdrive) to record either a new set of neurons every day or the same set of neurons over time. Ideally, microdrives should be easy to implant, allowing precise and smooth displacement of electrodes. The main caveat of most commercially available microdrives is their relatively short half-life span, in average ranging from weeks to a month. For most experiments, recording days-weeks is sufficient, but when the experiment depends on training animals for several months, it is crucial to develop new approaches. Here, we present a low-cost, reusable, and reimplantable device design as a solution to extend chronic recordings to long-term. This device is composed of a baseplate that is permanently fixed to the rodent's skull, as well as a reusable and replaceable microdrive that can be attached and detached from the baseplate, allowing its implantation and reimplantation. Reimplanting this microdrive is particularly convenient when no clear neuronal signal is present, or when the signal gradually decays across days. Our microdrive incorporates a mechanism for moving a 16 tungsten-wire bundle within a small (?15 mm3) lightweight device (?4 g). We present details of the design, manufacturing, and assembly processes. As a proof of concept, we show that recordings of the nucleus accumbens core (NAcc) in a freely behaving rat are stable over a month. Additionally, during a lever-press task, we found, as expected, that NAc single-unit activity was associated with rewarded lever presses. Furthermore, we also show that NAc shell (NAcSh) responses evoked by freely licking for sucrose, consistent with our previously published results, were conserved from a first implant to a second microdrive reimplant in the same rat, notably showing reimplantation is possible without overtly affecting the functional responses of the area of interest. In sum, here we present a novel microdrive design (low-cost, small size, and light weight) that can be used for long-term chronic recordings and reimplanted in freely behaving rats.

Project description:ObjectiveMicro-electrocorticography (μECoG) offers a minimally invasive neural interface with high spatial resolution over large areas of cortex. However, electrode arrays with many contacts that are individually wired to external recording systems are cumbersome and make recordings in freely behaving rodents challenging. We report a novel high-density 60-electrode system for μECoG recording in freely moving rats.ApproachMultiplexed headstages overcome the problem of wiring complexity by combining signals from many electrodes to a smaller number of connections. We have developed a low-cost, multiplexed recording system with 60 contacts at 406 μm spacing. We characterized the quality of the electrode signals using multiple metrics that tracked spatial variation, evoked-response detectability, and decoding value. Performance of the system was validated both in anesthetized animals and freely moving awake animals.Main resultsWe recorded μECoG signals over the primary auditory cortex, measuring responses to acoustic stimuli across all channels. Single-trial responses had high signal-to-noise ratios (SNR) (up to 25 dB under anesthesia), and were used to rapidly measure network topography within ∼10 s by constructing all single-channel receptive fields in parallel. We characterized evoked potential amplitudes and spatial correlations across the array in the anesthetized and awake animals. Recording quality in awake animals was stable for at least 30 days. Finally, we used these responses to accurately decode auditory stimuli on single trials.SignificanceThis study introduces (1) a μECoG recording system based on practical hardware design and (2) a rigorous analytical method for characterizing the signal characteristics of μECoG electrode arrays. This methodology can be applied to evaluate the fidelity and lifetime of any μECoG electrode array. Our μECoG-based recording system is accessible and will be useful for studies of perception and decision-making in rodents, particularly over the entire time course of behavioral training and learning.

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Long Term Amperometric Recordings in the Brain Extracellular Fluid of Freely Moving Immunocompromised NOD SCID Mice.

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