Wireless Programmable Recording and Stimulation of Deep Brain Activity in Freely Moving Humans.

Uncovering the neural mechanisms underlying human natural ambulatory behavior is a major challenge for neuroscience. Current commercially available implantable devices that allow for recording and stimulation of deep brain activity in humans can provide invaluable intrinsic brain signals but are not inherently designed for research and thus lack flexible control and integration with wearable sensors. We developed a mobile deep brain recording and stimulation (Mo-DBRS) platform that enables wireless and programmable intracranial electroencephalographic recording and electrical stimulation integrated and synchronized with virtual reality/augmented reality (VR/AR) and wearables capable of external measurements (e.g., motion capture, heart rate, skin conductance, respiration, eye tracking, and scalp EEG). When used in freely moving humans with implanted neural devices, this platform is adaptable to ecologically valid environments conducive to elucidating the neural mechanisms underlying naturalistic behaviors and to the development of viable therapies for neurologic and psychiatric disorders.

Fragile X mental retardation protein knockdown in the developing Xenopus tadpole optic tectum results in enhanced feedforward inhibition and behavioral deficits.

BACKGROUND: Fragile X Syndrome is the leading monogenetic cause of autism and most common form of intellectual disability. Previous studies have implicated changes in dendritic spine architecture as the primary result of loss of Fragile X Mental Retardation Protein (FMRP), but recent work has shown that neural proliferation is decreased and cell death is increased with either loss of FMRP or overexpression of FMRP. The purpose of this study was to investigate the effects of loss of FMRP on behavior and cellular activity. METHODS: We knocked down FMRP expression using morpholino oligos in the optic tectum of Xenopus laevis tadpoles and performed a series of behavioral and electrophysiological assays. We investigated visually guided collision avoidance, schooling, and seizure propensity. Using single cell electrophysiology, we assessed intrinsic excitability and synaptic connectivity of tectal neurons. RESULTS: We found that FMRP knockdown results in decreased swimming speed, reduced schooling behavior and decreased seizure severity. In single cells, we found increased inhibition relative to excitation in response to sensory input. CONCLUSIONS: Our results indicate that the electrophysiological development of single cells in the absence of FMRP is largely unaffected despite the large neural proliferation defect. The changes in behavior are consistent with an increase in inhibition, which could be due to either changes in cell number or altered inhibitory drive, and indicate that FMRP can play a significant role in neural development much earlier than previously thought.

FMRP regulates neurogenesis in vivo in Xenopus laevis tadpoles.

Fragile X Syndrome (FXS) is the leading known monogenic form of autism and the most common form of inherited intellectual disability. FXS results from silencing the FMR1 gene during embryonic development, leading to loss of Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein that regulates mRNA transport, stability, and translation. FXS is commonly thought of as a disease of synaptic dysfunction, however, FMRP expression is lost early in embryonic development, well before most synaptogenesis occurs. Recent studies suggest that loss of FMRP results in aberrant neurogenesis, but neurogenic defects have been variable. We investigated whether FMRP affects neurogenesis in Xenopus laevis tadpoles which express a homolog of FMR1. We used in vivo time-lapse imaging of neural progenitor cells and their neuronal progeny to evaluate the effect of acute loss or over-expression of FMRP on neurogenesis in the developing optic tectum. We complimented the time-lapse studies with SYTOX labeling to quantify apoptosis and CldU labeling to measure cell proliferation. Animals with increased or decreased levels of FMRP have significantly decreased neuronal proliferation and survival. They also have increased neuronal differentiation, but deficient dendritic arbor elaboration. The presence and severity of these defects was highly sensitive to FMRP levels. These data demonstrate that FMRP plays an important role in neurogenesis and suggest that endogenous FMRP levels are carefully regulated. These studies show promise in using Xenopus as an experimental system to study fundamental deficits in brain development with loss of FMRP and give new insight into the pathophysiology of FXS.