High-throughput behavioral training of rodents has been a transformative development for systems neuroscience. Water or food restriction is typically required to motivate task engagement. We hypothesized a gap between physiological water need and hedonic water satiety that could be leveraged to train rats for water rewards without water restriction. We show that when Citric Acid (CA) is added to water, female rats drink less, yet consume enough to maintain long term health. With 24 h/day access to a visual task with water rewards, rats with ad lib CA water performed 84% ± 18% as many trials as in the same task under water restriction. In 2-h daily sessions, rats with ad lib CA water performed 68% ± 13% as many trials as under water restriction. Using reward sizes <25 μl, rats with ad lib CA performed 804 ± 285 trials/day in live-in sessions or 364 ± 82 trials/day in limited duration daily sessions. The safety of CA water amendment was previously shown for male rats, and the gap between water need and satiety was similar to what we observed in females. Therefore, it is likely that this method will generalize to male rats, though this remains to be shown. We conclude that at least in some contexts rats can be trained using water rewards without water restriction, benefitting both animal welfare and scientific productivity.

In the laboratory, animals' motivation to work tends to be positively correlated with reward magnitude. But in nature, rewards earned by work are essential to survival (e.g., working to find water), and the payoff of that work can vary on long timescales (e.g., seasonally). Under these constraints, the strategy of working less when rewards are small could be fatal. We found that instead, rats in a closed economy did more work for water rewards when the rewards were stably smaller, a phenomenon also observed in human labor supply curves. Like human consumers, rats showed elasticity of demand, consuming far more water per day when its price in effort was lower. The neural mechanisms underlying such "rational" market behaviors remain largely unexplored. We propose a dynamic utility maximization model that can account for the dependence of rat labor supply (trials/day) on the wage rate (milliliter/trial) and also predict the temporal dynamics of when rats work. Based on data from mice, we hypothesize that glutamatergic neurons in the subfornical organ in lamina terminalis continuously compute the instantaneous marginal utility of voluntary work for water reward and causally determine the amount and timing of work.

Upon completion of an experiment, if a trend is observed that is "not quite significant," it can be tempting to collect more data in an effort to achieve statistical significance. Such sample augmentation or "N-hacking" is condemned because it can lead to an excess of false positives, which can reduce the reproducibility of results. However, the scenarios used to prove this rule tend to be unrealistic, assuming the addition of unlimited extra samples to achieve statistical significance, or doing so when results are not even close to significant; an unlikely situation for most experiments involving patient samples, cultured cells, or live animals. If we were to examine some more realistic scenarios, could there be any situations where N-hacking might be an acceptable practice? This Essay aims to address this question, using simulations to demonstrate how N-hacking causes false positives and to investigate whether this increase is still relevant when using parameters based on real-life experimental settings.

A stochastic visual motion discrimination task is widely used to study rapid decision-making in humans and animals. Among trials of the same sensory difficulty within a block of fixed decision strategy, humans and monkeys are widely reported to make more errors in the individual trials with longer reaction times. This finding has posed a challenge for the drift-diffusion model of sensory decision-making, which in its basic form predicts that errors and correct responses should have the same reaction time distributions. We previously reported that rats also violate this model prediction, but in the opposite direction: for rats, motion discrimination accuracy was highest in the trials with the longest reaction times. To rule out task differences as the cause of our divergent finding in rats, the present study tested humans and rats using the same task and analyzed their data identically. We confirmed that rats' accuracy increased with reaction time, whereas humans' accuracy decreased with reaction time in the same task. These results were further verified using a new temporally local analysis method, ruling out that the observed trend was an artifact of non-stationarity in the data of either species. The main effect was found whether the signal strength (motion coherence) was varied in randomly interleaved trials or held constant within a block. The magnitude of the effects increased with motion coherence. These results provide new constraints useful for refining and discriminating among the many alternative mathematical theories of decision-making.

The latency of visual responses generally decreases as contrast increases. Recording in the lateral geniculate nucleus (LGN), we find that response latency increases with increasing contrast in ON cells for some visual stimuli. We propose that this surprising latency trend can be explained if ON cells rest further from threshold at higher contrasts. Indeed, while contrast changes caused a combination of multiplicative gain change and additive shift in LGN cells, the additive shift predominated in ON cells. Modeling results supported this theory: the ON cell latency trend was found when the distance-to-threshold shifted with contrast, but not when distance-to-threshold was fixed across contrasts. In the model, latency also increases as surround-to-center ratios increase, which has been shown to occur at higher contrasts. We propose that higher-contrast full-field stimuli can evoke more surround inhibition, shifting the potential further from spiking threshold and thereby increasing response latency.

When observers make rapid, difficult perceptual decisions, their response time is highly variable from trial to trial. In a visual motion discrimination task, it has been reported that human accuracy declines with increasing response time, whereas rat accuracy increases with response time. This is of interest because different mathematical theories of decision-making differ in their predictions regarding the correlation of accuracy with response time. On the premise that perceptual decision-making mechanisms are likely to be conserved among mammals, we seek to unify the rodent and primate results in a common theoretical framework. We show that a bounded drift diffusion model (DDM) can explain both effects with variable parameters: trial-to-trial variability in the starting point of the diffusion process produces the pattern typically observed in rats, whereas variability in the drift rate produces the pattern typically observed in humans. We further show that the same effects can be produced by deterministic biases, even in the absence of parameter stochasticity or parameter change within a trial.

The pigmented rat is an increasingly important model in visual neuroscience research, yet the lamination of retinal projections in the dLGN has not been examined in sufficient detail. From previous studies it was known that most of the rat dLGN receives monocular input from the contralateral eye, with a small island receiving predominantly ipsilateral projections. Here we revisit the question using cholera toxin B subunit, a tracer that efficiently fills retinal terminals after intra-ocular injection. We imaged retinal termini throughout the dLGN at 0.5 μm resolution and traced areas of ipsilateral and contralateral terminals to obtain a high resolution 3D reconstruction of the projection pattern. Retinal termini in the dLGN are well segregated by eye of origin, as expected. We find, however, that the ipsilateral projections form multiple discrete projection zones in three dimensions, not the single island previously described. It remains to be determined whether these subdomains represent distinct functional sublaminae, as is the case in other mammals.