Chronically-implanted Neuropixels probes enable high yield recordings in freely moving mice

The advent of high-yield electrophysiology using Neuropixels probes is now enabling researchers to simultaneously record hundreds of neurons with remarkably high signal to noise. However, these probes have not been well-suited to use in freely moving mice. It is critical to study neural activity in unrestricted animals for many reasons, such as leveraging ethological approaches to study neural circuits. We designed and implemented a novel device that allows Neuropixels probes to be customized for chronically-implanted experiments in freely moving mice. We demonstrate the ease and utility of this approach in recording hundreds of neurons during an ethological behavior across weeks of experiments. We provide the technical drawings and procedures for other researchers to do the same. Importantly, our approach enables researchers to explant and reuse these valuable probes, a transformative step which has not been established for recordings with any type of chronically-implanted probe

Chronically-implanted Neuropixels probes enable high yield recordings in freely moving mice: dataset

The advent of high-yield electrophysiology using Neuropixels probes is now enabling researchers to simultaneously record hundreds of neurons with remarkably high signal to noise. However, these probes have not been well-suited to use in freely moving mice. It is critical to study neural activity in unrestricted animals for many reasons, such as leveraging ethological approaches to study neural circuits. We designed and implemented a novel device that allows Neuropixels probes to be customized for chronically-implanted experiments in freely moving mice. We demonstrate the ease and utility of this approach in recording hundreds of neurons during an ethological behavior across weeks of experiments. We provide the technical drawings and procedures for other researchers to do the same. Importantly, our approach enables researchers to explant and reuse these valuable probes, a transformative step which has not been established for recordings with any type of chronically-implanted probe

Integration of Direction Cues Is Invariant to the Temporal Gap between Them

Many decisions involve integration of evidence conferred by discrete cues over time. However, the neural mechanism of this integration is poorly understood. Several decision-making models suggest that integration of evidence is implemented by a dynamic system whose state evolves toward a stable point representing the decision outcome. The internal dynamics of such point attractor models render them sensitive to the temporal gaps between cues because their internal forces push the state forward once it is dislodged from the initial stable point. We asked whether human subjects are as sensitive to such temporal gaps. Subjects reported the net direction of stochastic random dot motion, which was presented in one or two brief observation windows (pulses). Pulse strength and interpulse interval varied randomly from trial to trial. We found that subjects' performance was largely invariant to the interpulse intervals up to at least 1 s. The findings question the implementation of the integration process via mechanisms that rely on autonomous changes of network state. The mechanism should be capable of freezing the state of the network at a variety of firing rate levels during temporal gaps between the cues, compatible with a line of stable attractor states

Dataset from: Lapses in perceptual decisions reflect exploration.

Perceptual decision-makers often display a constant rate of errors independent of evidence strength. These “lapses” are treated as a nuisance arising from noise tangential to the decision, e.g. inattention or motor errors. Here, we use a multisensory decision task in rats to demonstrate that these explanations cannot account for lapses’ stimulus dependence. We propose a novel explanation: lapses reflect a strategic trade-off between exploiting known rewarding actions and exploring uncertain ones. We tested the model’s predictions by selectively manipulating one action’s reward magnitude or probability. As uniquely predicted by this model, changes were restricted to lapses associated with that action. Finally, we show that lapses are a powerful tool for assigning decision-related computations to neural structures based on disruption experiments (here, posterior striatum and secondary motor cortex). These results suggest that lapses reflect an integral component of decision-making and are informative about action values in normal and disrupted brain states

The Cost of Accumulating Evidence in Perceptual Decision Making

Decision making often involves the accumulation of information over time, but acquiring information typically comes at a cost. Little is known about the cost incurred by animals and humans for acquiring additional information from sensory variables due, for instance, to attentional efforts. Through a novel integration of diffusion models and dynamic programming, we were able to estimate the cost of making additional observations per unit of time from two monkeys and six humans in a reaction time (RT) random-dot motion discrimination task. Surprisingly, we find that the cost is neither zero nor constant over time, but for the animals and humans features a brief period in which it is constant but increases thereafter. In addition, we show that our theory accurately matches the observed reaction time distributions for each stimulus condition, the time-dependent choice accuracy both conditional on stimulus strength and independent of it, and choice accuracy and mean reaction times as a function of stimulus strength. The theory also correctly predicts that urgency signals in the brain should be independent of the difficulty, or stimulus strength, at each trial

Posterior parietal cortex guides visual decisions in rats

Neurons in putative decision-making structures can reflect both sensory and decision signals, making their causal role in decisions unclear. Here, we tested whether rat posterior parietal cortex (PPC) is causal for processing visual sensory signals or instead for accumulating evidence for decision alternatives. We optogenetically disrupted PPC activity during decision-making and compared effects on decisions guided by auditory vs. visual evidence. Deficits were largely restricted to visual decisions. To further test for visual dominance in PPC, we evaluated electrophysiological responses following individual sensory events and observed much larger response modulation following visual stimuli than auditory stimuli. Finally, we measured trial-to-trial spike count variability during stimulus presentation and decision formation. Variability sharply decreased, suggesting the network is stabilized by inputs, unlike what would be expected if sensory signals were locally accumulated. Our findings argue that PPC plays a causal role in processing visual signals that are accumulated elsewhere.SIGNIFICANCE STATEMENTDefining the neural circuits that support decision-making bridges a gap between our understanding of simple sensorimotor reflexes and our understanding of truly complex behavior. However, identifying brain areas which play a causal role in decision-making has proved challenging. We tested the causal role of a candidate component of decision circuits, the rat posterior parietal cortex (PPC). Our interpretation of the data benefitted from our use of animals trained to make decisions guided by either visual or auditory evidence. Our results argue that PPC plays a causal role specifically in visual decision-making, and that PPC may support sensory aspects of the decision, such as interpreting the visual signals so that evidence for a decision can be accumulated elsewhere

Dataset from: Visual evidence accumulation guides decision-making in unrestrained mice.

The ability to manipulate neural activity with precision is an asset in uncovering neural circuits for decision-making. Diverse tools for manipulating neurons are available for mice, but their feasibility remains unclear, especially when decisions require accumulating visual evidence. For example, whether mice' decisions reflect leaky accumulation is unknown, as are the relevant/irrelevant factors that influence decisions. Further, causal circuits for visual evidence accumulation are poorly understood. To address this, we measured decisions in mice judging the fluctuating rate of a flash sequence. An initial analysis (>500,000 trials, 29 male and female mice) demonstrated that information throughout the 1000 ms trial influenced choice, with early information most influential. This suggests that information persists in neural circuits for ∼1000 ms with minimal accumulation leak. Next, in a subset of animals, we probed strategy more extensively and found that although animals were influenced by stimulus rate, they were unable to entirely suppress the influence of stimulus brightness. Finally, we identified anteromedial (AM) visual area via retinotopic mapping and optogenetically inhibited it using JAWS. Light activation biased choices in both injected and uninjected animals, demonstrating that light alone influences behavior. By varying stimulus–response contingency while holding stimulated hemisphere constant, we surmounted this obstacle to demonstrate that AM suppression biases decisions. By leveraging a large dataset to quantitatively characterize decision-making behavior, we establish mice as suitable for neural circuit manipulation studies. Further, by demonstrating that mice accumulate visual evidence, we demonstrate that this strategy for reducing uncertainty in decision-making is used by animals with diverse visual systems

Stability Analysis of Asynchronous States in Neuronal Networks with Conductance-Based Inhibition

Oscillations in networks of inhibitory interneurons have been reported at various sites of the brain and are thought to play a fundamental role in neuronal processing. This Letter provides a self-contained analytical framework that allows numerically efficient calculations of the population activity of a network of conductance-based integrate-and-fire neurons that are coupled through inhibitory synapses. Based on a normalization equation this Letter introduces a novel stability criterion for a network state of asynchronous activity and discusses its perturbations. The analysis shows that, although often neglected, the reversal potential of synaptic inhibition has a strong influence on the stability as well as the frequency of network oscillations

Can we identify non-stationary dynamics of trial-to-trial variability?"

Identifying sources of the apparent variability in non-stationary scenarios is a fundamental problem in many biological data analysis settings. For instance, neurophysiological responses to the same task often vary from each repetition of the same experiment (trial) to the next. The origin and functional role of this observed variability is one of the fundamental questions in neuroscience. The nature of such trial-to-trial dynamics however remains largely elusive to current data analysis approaches. A range of strategies have been proposed in modalities such as electro-encephalography but gaining a fundamental insight into latent sources of trial-to-trial variability in neural recordings is still a major challenge. In this paper, we present a proof-of-concept study to the analysis of trial-to-trial variability dynamics founded on non-autonomous dynamical systems. At this initial stage, we evaluate the capacity of a simple statistic based on the behaviour of trajectories in classification settings, the trajectory coherence, in order to identify trial-to-trial dynamics. First, we derive the conditions leading to observable changes in datasets generated by a compact dynamical system (the Duffing equation). This canonical system plays the role of a ubiquitous model of non-stationary supervised classification problems. Second, we estimate the coherence of class-trajectories in empirically reconstructed space of system states. We show how this analysis can discern variations attributable to non-autonomous deterministic processes from stochastic fluctuations. The analyses are benchmarked using simulated and two different real datasets which have been shown to exhibit attractor dynamics. As an illustrative example, we focused on the analysis of the rat's frontal cortex ensemble dynamics during a decision-making task. Results suggest that, in line with recent hypotheses, rather than internal noise, it is the deterministic trend which most likely underlies the observed trial-to-trial variability. Thus, the empirical tool developed within this study potentially allows us to infer the source of variability in in-vivo neural recordings