The “sewing machine” for minimally invasive neural recording, bioRxiv, 2019-03-15

AbstractWe present a system for scalable and customizable recording and stimulation of neural activity. In large animals and humans, the current benchmark for high spatial and temporal resolution neural interfaces are fixed arrays of wire or silicon electrodes inserted into the parenchyma of the brain. However, probes that are large and stiff enough to penetrate the brain have been shown to cause acute and chronic damage and inflammation, which limits their longevity, stability, and yield. One approach to this problem is to separate the requirements of the insertion device, which should to be as stiff as possible, with the implanted device, which should be as small and flexible as possible. Here, we demonstrate the feasibility and scalability of this approach with a system incorporating fine and flexible thin-film polymer probes, a fine and stiff insertion needle, and a robotic insertion machine. Together the system permits rapid and precise implantation of probes, each individually targeted to avoid observable vasculature and to attain diverse anatomical targets. As an initial demonstration of this system, we implanted arrays of electrodes in rat somatosensory cortex, recorded extracellular action potentials from them, and obtained histological images of the tissue response. This approach points the way toward a new generation of scaleable, stable, and safe neural interfaces, both for the basic scientific study of brain function and for clinical applications.

biorxiv neuroscience 200-500-users 2019

Dopamine transients delivered in learning contexts do not act as model-free prediction errors, bioRxiv, 2019-03-12

AbstractDopamine neurons fire transiently in response to unexpected rewards. These neural correlates are proposed to signal the reward prediction error described in model-free reinforcement learning algorithms. This error term represents the unpredicted or ‘excess’ value of the rewarding event. In model-free reinforcement learning, this value is then stored as part of the learned value of any antecedent cues, contexts or events, making them intrinsically valuable, independent of the specific rewarding event that caused the prediction error. In support of equivalence between dopamine transients and this model-free error term, proponents cite causal optogenetic studies showing that artificially induced dopamine transients cause lasting changes in behavior. Yet none of these studies directly demonstrate the presence of cached value under conditions appropriate for associative learning. To address this gap in our knowledge, we conducted three studies where we optogenetically activated dopamine neurons while rats were learning associative relationships, both with and without reward. In each experiment, the antecedent cues failed to acquired value and instead entered into value-independent associative relationships with the other cues or rewards. These results show that dopamine transients, constrained within appropriate learning situations, support valueless associative learning.

biorxiv neuroscience 100-200-users 2019

Blue light induces neuronal-activity-regulated gene expression in the absence of optogenetic proteins, bioRxiv, 2019-03-09

Optogenetics is widely used to control diverse cellular functions with light, requiring experimenters to expose cells to bright light. Because extended exposure to visible light can be toxic to cells, it is important to characterize the effects of light stimulation on cellular function in the absence of exogenous optogenetic proteins. Here we exposed cultured mouse cortical neurons that did not express optogenetic proteins to several hours of flashing blue, red, or green light. We found that exposing neurons to as short as one hour of blue, but not red or green, light results in the induction of neuronal-activity-regulated genes without inducing neuronal activity. Our findings suggest blue light stimulation is ill-suited to long-term optogenetic experiments, especially those that measure transcription.Significance StatementOptogenetics is widely used to control cellular functions using light. In neuroscience, channelrhodopsins, exogenous light-sensitive channels, are used to achieve light-dependent control of neuronal firing. This optogenetic control of neuronal firing requires exposing neurons to high-powered light. We ask how this light exposure, in the absence of channelrhodopsin, affects the expression of neuronal-activity-regulated genes, i.e., the genes that are transcribed in response to neuronal stimuli. Surprisingly, we find that neurons without channelrhodopsin express neuronal-activity-regulated genes in response to as short as an hour of blue, but not red or green, light exposure. These findings suggest that experimenters wishing to achieve longer-term (an hour or more) optogenetic control over neuronal firing should avoid using systems that require blue light.

biorxiv neuroscience 200-500-users 2019

 

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