The biophysical properties of existing optogenetic tools constrain the scale, speed, and fidelity of precise optogenetic control. Here, we use structure-guided mutagenesis to engineer opsins that exhibit very high pot...
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The biophysical properties of existing optogenetic tools constrain the scale, speed, and fidelity of precise optogenetic control. Here, we use structure-guided mutagenesis to engineer opsins that exhibit very high potency while retaining fast kinetics. These new opsins enable large-scale, temporally and spatially precise control of population neural activity. We extensively benchmark these new opsins against existing optogenetic tools and provide a detailed biophysical characterization of a diverse family of opsins under two-photon illumination. This establishes a resource for matching the optimal opsin to the goals and constraints of patterned optogenetics experiments. Finally, by combining these new opsins with optimized procedures for holographic photostimulation, we demonstrate the simultaneous coactivation of several hundred spatially defined neurons with a single hologram and nearly double that number by temporally interleaving holograms at fast rates. These newly engineered opsins substantially extend the capabilities of patterned illumination optogenetic paradigms for addressing neural circuits and behavior.
Regulating energy metabolism is critical to maintain homeostasis of cellular and systemic functions. In the brain, specialised centres for energy storage regulation finely communicate with the periphery and integrate ...
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Regulating energy metabolism is critical to maintain homeostasis of cellular and systemic functions. In the brain, specialised centres for energy storage regulation finely communicate with the periphery and integrate signals about internal states. As a result, the behavioural responses can be directly adjusted accordingly to the energetic demands. In the fruit fly Drosophila melanogaster, one of these regulatory centres is the mushroom bodies (MBs), a brain region involved in olfactory memory. The integration of metabolic cues by the MBs has a crucial impact on learned behaviour. In this review, we explore recent advances supporting the interplay between energy metabolism and memory establishment, as well as the instructive role of energy during the switch between memory phases.
Sensory areas are spontaneously active in the absence of sensory stimuli. This spontaneous activity has long been studied;however, its functional role remains largely unknown. Recent advances in technology, allowing l...
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Sensory areas are spontaneously active in the absence of sensory stimuli. This spontaneous activity has long been studied;however, its functional role remains largely unknown. Recent advances in technology, allowing large-scale neural recordings in the awake and behaving animal, have transformed our understanding of spontaneous activity. Studies using these recordings have discovered high-dimensional spontaneous activity patterns, correlation between spontaneous activity and behavior, and dissimilarity between spontaneous and sensory-driven activity patterns. These findings are supported by evidence from developing animals, where a transition toward these characteristics is observed as the circuit matures, as well as by evidence from mature animals across species. These newly revealed characteristics call for the formulation of a new role for spontaneous activity in neural sensory computation.
The mammalian retina engages a broad array of linear and nonlinear circuit mechanisms to convert natural scenes into retinal ganglion cell (RGC) spike outputs. Although many individual integration mechanisms are well ...
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The mammalian retina engages a broad array of linear and nonlinear circuit mechanisms to convert natural scenes into retinal ganglion cell (RGC) spike outputs. Although many individual integration mechanisms are well understood, we know less about how multiple mechanisms interact to encode the complex spatial features present in natural inputs. Here, we identified key spatial features in natural scenes that shape encoding by primate parasol RGCs. Our approach identified simplifications in the spatial structure of natural scenes that minimally altered RGC spike responses. We observed that reducing natural movies into 16 linearly integrated regions described similar to 80% of the structure of parasol RGC spike responses;this performance depended on the number of regions but not their precise spatial locations. We used simplified stimuli to design high-dimensional metamers that recapitulated responses to naturalistic movies. Finally, we modeled the retinal computations that convert flashed natural images into one-dimensional spike counts.
Background:Flight and freezing are two vital defensive behaviors that mice display to avoid natural *** they are exposed to innate threats,visual cues are processed and transmitted by the visual system into the emotio...
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Background:Flight and freezing are two vital defensive behaviors that mice display to avoid natural *** they are exposed to innate threats,visual cues are processed and transmitted by the visual system into the emotional nuclei and finally transmitted to the periaqueductal gray(PAG)to induce defensive ***,how the dorsal PAG(dPAG)encodes the two defensive behaviors is ***:Multi-array electrodes were implanted in the dPAG nuclei of C57BL/6 *** kinds of visual stimuli(looming and sweeping)were used to induce defensive behaviors in *** signals under different defense behaviors were recorded,and the encoding characteristics of the two behaviors were extracted and analyzed from spike firing and frequency ***,synchronization of neural activity during the defense process was ***:The neural activity between flight and freezing behaviors showed different firing patterns,and the differences in the inter-spike interval distribution were mainly reflected in the 2–10 ms *** frequency band activities under both defensive behaviors were concentrated in the theta band;the active frequency of flight was~8to 10 Hz,whereas that of freezing behavior was~6 to 8 *** network connection density under both defense behaviors was significantly higher than the period before and after defensive behavior occurred,indicating that there was a high synchronization of neural activity during the defense ***:The dPAG nuclei of mice have different coding features between flight and freezing behaviors;during strong looming stimulation,fast neuro-i nstinctive decision making is required while encountering weak sweeping stimulation,and computable planning late behavior is predicted in the early *** frequency band activities under both defensive behaviors were concentrated in the theta *** was a high synchronization of neural activity during the defense process,which may be a key factor trigg
We study how stimulus information can be represented in the dynamical signatures of an oscillatory model of neural activity-a model whose activity can be modulated by input akin to signals involved in working memory (...
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We study how stimulus information can be represented in the dynamical signatures of an oscillatory model of neural activity-a model whose activity can be modulated by input akin to signals involved in working memory (WM). We developed a neural field model, tuned near an oscillatory instability, in which the WM-like input can modulate the frequency and amplitude of the oscillation. Our neural field model has a spatial-like domain in which an input that preferentially targets a point-a stimulus feature-on the domain will induce feature-specific activity changes. These feature-specific activity changes affect both the mean rate of spikes and the relative timing of spiking activity to the global field oscillation-the phase of the spiking activity. From these two dynamical signatures, we define both a spike rate code and an oscillatory phase code. We assess the performance of these two codes to discriminate stimulus features using an information-theoretic analysis. We show that global WM input modulations can enhance phase code discrimination while simultaneously reducing rate code discrimination. Moreover, we find that the phase code performance is roughly two orders of magnitude larger than that of the rate code defined for the same model solutions. The results of our model have applications to sensory areas of the brain, to which prefrontal areas send inputs reflecting the content of WM. These WM inputs to sensory areas have been established to induce oscillatory changes similar to our model. Our model results suggest a mechanism by which WM signals may enhance sensory information represented in oscillatory activity beyond the comparatively weak representations based on the mean rate activity.
The response of a set of neurons in an area is the result of the sensory input, the interaction of the neurons within the area as well as the long range interactions between areas. We aimed to study the relation betwe...
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The response of a set of neurons in an area is the result of the sensory input, the interaction of the neurons within the area as well as the long range interactions between areas. We aimed to study the relation between interactions among multiple areas, and if they are fixed or dynamic. The structural connectivity provides a substrate for these interactions, but anatomical connectivity is not known in sufficient detail and it only gives us a static picture. Using the Allen Brain Observatory Visual coding Neuropixels dataset, which includes simultaneous recordings of spiking activity from up to 6 hierarchically organized mouse cortical visual areas, we estimate the functional connectivity between neurons using a linear model of responses to flashed static grating stimuli. We characterize functional connectivity between populations via interaction subspaces. We find that distinct subspaces of a source area mediate interactions with distinct target areas, supporting the notion that cortical areas use distinct channels to communicate. Most importantly, using a piecewise linear model for activity within each trial, we find that these interactions evolve dynamically over tens of milliseconds following a stimulus presentation. Inter-areal subspaces become more aligned with the intra-areal subspaces during epochs in which a feedforward wave of activity propagates through visual cortical areas. When the short-term dynamics are averaged over, we find that the interaction subspaces are stable over multiple stimulus blocks. These findings have important implications for understanding how information flows through biological neural networks composed of interconnected modules, each of which may have a distinct functional specialization.
Modern neural recording methodologies, including multi-electrode and optical recordings, allow us to monitor the large population of neurons with high temporal resolution. Such recordings provide rich datasets that ar...
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Modern neural recording methodologies, including multi-electrode and optical recordings, allow us to monitor the large population of neurons with high temporal resolution. Such recordings provide rich datasets that are expected to understand better how information about the external world is internally represented and how these representations are altered over time. Achieving this goal requires the development of novel pattern recognition methods and/or the application of existing statistical methods in novel ways to gain insights into basic neural computational principles. In this dissertation, I will take this data-driven approach to dissect the role of short-term memory in olfactory signal processing in two relatively simple models of the olfactory system: fruit fly (Drosophila melanogaster) and locust (Schistocerca americana). First, I will focus on understanding how odor representations within a single stimulus exposure are refined across different populations of neurons (faster dynamics; on the order seconds) in the early olfactory circuits. Using light-sheet imaging datasets from transgenic flies expressing calcium indicators in select populations of neurons, I will reveal how odor representations are decorrelated over time in different neural populations. Further, I will examine how this computation is altered by short-term memory in this neural circuitry. Next, I will examine how neural representations for odorants at an ensemble level are altered across different exposures (slower dynamics; on the order of tens of seconds to minutes). I will examine the role of this short-term adaptation in altering neural representations for odor identity and intensity. Lastly, I will present approaches to help achieve robustness against both extrinsic and intrinsic perturbations of odor-evoked neural responses. I will conclude with a Boolean neural network inspired by the insect olfactory system and compare its performance against other state-of-the-art methods on standa
Merkel cells (MCs) and associated primary sensory afferents of the whisker follicle-sinus complex, accurately code whisker self-movement, angle, and whisk phase during whisking. However, little is known about their ro...
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Merkel cells (MCs) and associated primary sensory afferents of the whisker follicle-sinus complex, accurately code whisker self-movement, angle, and whisk phase during whisking. However, little is known about their roles played in cortical encoding of whisker movement. To this end, the spiking activity of primary somatosensory barrel cortex (wS1) neurons was measured in response to varying the whisker deflection amplitude and velocity in transgenic mice with previously established reduced mechanoelectrical coupling at MC-associated afferents. Under reduced MC activity, wS1 neurons exhibited increased sensitivity to whisker deflection. This appeared to arise from a lack of variation in response magnitude to varying the whisker deflection amplitude and velocity. This latter effect was further indicated by weaker variation in the temporal profile of the evoked spiking activity when either whisker deflection amplitude or velocity was varied. Nevertheless, under reduced MC activity, wS1 neurons retained the ability to differentiate stimulus features based on the timing of their first post-stimulus spike. Collectively, results from this study suggest that MCs contribute to cortical encoding of both whisker amplitude and velocity, predominantly by tuning wS1 response magnitude, and by patterning the evoked spiking activity, rather than by tuning wS1 response latency.
Transmitting information in engineered neural communication systems is a promising solution for delay-sensitive applications in the internet of bio-nano things (IoBNTs). As widely used in wired and wireless communicat...
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ISBN:
(纸本)9781450398671
Transmitting information in engineered neural communication systems is a promising solution for delay-sensitive applications in the internet of bio-nano things (IoBNTs). As widely used in wired and wireless communication systems, multiplexing could also improve channel transmission efficiency for neural communication systems. In this paper, we model a neural communication system for IoBNTs and propose a neural signal multiplexing scheme for this system. It is a frequency-division multiplexing (FDM) based multiplexing strategy. The multiplexing, demultiplexing scheme, as well as decoding method are presented. The performance of the proposed strategy is evaluated and analyzed in terms of bit error rate and mutual information rate. The work can help researchers better understanding the underlying mechanism of neural multiplexing and pave the way for the implementation of IoBNT applications.
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