Spatial maps in piriform cortex during olfactory navigation.

Odors are a fundamental part of the sensory environment used by animals to inform behaviors such as foraging and navigation. Primary olfactory (piriform) cortex is thought to be dedicated to encoding odor identity. Here, using neural ensemble recordings in freely moving rats performing a novel odor-cued spatial choice task, we show that posterior piriform cortex neurons also carry a robust spatial map of the environment.

Maturation of cortical input to dorsal raphe nucleus increases behavioral persistence in mice.

The ability to persist toward a desired objective is a fundamental aspect of behavioral control whose impairment is implicated in several behavioral disorders. One of the prominent features of behavioral persistence is that its maturation occurs relatively late in development. This is presumed to echo the developmental time course of a corresponding circuit within late-maturing parts of the brain, such as the prefrontal cortex, but the specific identity of the responsible circuits is unknown.

Serotonin.

Serotonin, also known as 5-hydroxytryptamine or 5-HT, is a neuromodulator widely recognized for its role in various psychoactive drugs. These drugs can exhibit antidepressant, antipsychotic, anxiolytic, empathogenic, or psychedelic effects, depending on their specific interactions with the serotonin system as well as other neuromodulators such as noradrenaline, dopamine, and oxytocin. This has led to a widespread belief that the neurochemical processes taking place deep inside our brains affect our subjective experiences and mental health.

A reservoir of foraging decision variables in the mouse brain.

In any given situation, the environment can be parsed in different ways to yield decision variables (DVs) defining strategies useful for different tasks. It is generally presumed that the brain only computes a single DV defining the current behavioral strategy. Here to test this assumption, we recorded neural ensembles in the frontal cortex of mice performing a foraging task admitting multiple DVs.

Next-generation brain observatories.

We propose centralized brain observatories for large-scale recordings of neural activity in mice and non-human primates coupled with cloud-based data analysis and sharing. Such observatories will advance reproducible systems neuroscience and democratize access to the most advanced tools and data.

An olfactory self-test effectively screens for COVID-19.

Background: Key to curtailing the COVID-19 pandemic are wide-scale screening strategies. An ideal screen is one that would not rely on transporting, distributing, and collecting physical specimens. Given the olfactory impairment associated with COVID-19, we developed a perceptual measure of olfaction that relies on smelling household odorants and rating them online.

Stress-sensitive inference of task controllability.

Estimating the controllability of the environment enables agents to better predict upcoming events and decide when to engage controlled action selection. How does the human brain estimate controllability? Trial-by-trial analysis of choices, decision times and neural activity in an explore-and-predict task demonstrate that humans solve this problem by comparing the predictions of an 'actor' model with those of a reduced 'spectator' model of their environment. Neural blood oxygen level-dependent responses within striatal and medial prefrontal areas tracked the instantaneous difference in the prediction errors generated by these two statistical learning models.

Spatial maps in piriform cortex during olfactory navigation.

Odours are a fundamental part of the sensory environment used by animals to guide behaviours such as foraging and navigation. Primary olfactory (piriform) cortex is thought to be the main cortical region for encoding odour identity. Here, using neural ensemble recordings in freely moving rats performing an odour-cued spatial choice task, we show that posterior piriform cortex neurons carry a robust spatial representation of the environment.

Metastable attractors explain the variable timing of stable behavioral action sequences.

The timing of self-initiated actions shows large variability even when they are executed in stable, well-learned sequences. Could this mix of reliability and stochasticity arise within the same neural circuit? We trained rats to perform a stereotyped sequence of self-initiated actions and recorded neural ensemble activity in secondary motor cortex (M2), which is known to reflect trial-by-trial action-timing fluctuations. Using hidden Markov models, we established a dictionary between activity patterns and actions.

Standardized and reproducible measurement of decision-making in mice.

Progress in science requires standardized assays whose results can be readily shared, compared, and reproduced across laboratories. Reproducibility, however, has been a concern in neuroscience, particularly for measurements of mouse behavior. Here, we show that a standardized task to probe decision-making in mice produces reproducible results across multiple laboratories.

Citric Acid Water as an Alternative to Water Restriction for High-Yield Mouse Behavior.

Powerful neural measurement and perturbation tools have positioned mice as an ideal species for probing the neural circuit mechanisms of cognition. Crucial to this success is the ability to motivate animals to perform specific behaviors. One successful strategy is to restrict their water intake, rewarding them with water during a behavioral task.

Phasic Activation of Dorsal Raphe Serotonergic Neurons Increases Pupil Size.

Transient variations in pupil size (PS) under constant luminance are coupled to rapid changes in arousal state, which have been interpreted as vigilance, salience, or a surprise signal. Neural control of such fluctuations presumably involves multiple brain regions and neuromodulatory systems, but it is often associated with phasic activity of the noradrenergic system. Serotonin (5-HT), a neuromodulator also implicated in aspects of arousal such as sleep-wake transitions, motivational state regulation, and signaling of unexpected events, seems to affect PS, but these effects have not been investigated in detail.

The impact of learning on perceptual decisions and its implication for speed-accuracy tradeoffs.

In standard models of perceptual decision-making, noisy sensory evidence is considered to be the primary source of choice errors and the accumulation of evidence needed to overcome this noise gives rise to speed-accuracy tradeoffs. Here, we investigated how the history of recent choices and their outcomes interact with these processes using a combination of theory and experiment. We found that the speed and accuracy of performance of rats on olfactory decision tasks could be best explained by a Bayesian model that combines reinforcement-based learning with accumulation of uncertain sensory evidence.

Relationship between odor intensity estimates and COVID-19 prevalence prediction in a Swedish population.

In response to the COVID-19 pandemic, countries have implemented various strategies to reduce and slow the spread of the disease in the general population. For countries that have implemented restrictions on its population in a step-wise manner, monitoring of COVID-19 prevalence is of importance to guide decision on when to impose new, or when to abolish old, restrictions. We are here determining whether measures of odor intensity in a large sample can serve as one such measure.

Inference-Based Decisions in a Hidden State Foraging Task: Differential Contributions of Prefrontal Cortical Areas.

Essential features of the world are often hidden and must be inferred by constructing internal models based on indirect evidence. Here, to study the mechanisms of inference, we establish a foraging task that is naturalistic and easily learned yet can distinguish inference from simpler strategies such as the direct integration of sensory data. We show that both mice and humans learn a strategy consistent with optimal inference of a hidden state.

Learning optimal decisions with confidence.

Diffusion decision models (DDMs) are immensely successful models for decision making under uncertainty and time pressure. In the context of perceptual decision making, these models typically start with two input units, organized in a neuron-antineuron pair. In contrast, in the brain, sensory inputs are encoded through the activity of large neuronal populations.

The mechanistic foundation of Weber's law.

Although Weber's law is the most firmly established regularity in sensation, no principled way has been identified to choose between its many proposed explanations. We investigated Weber's law by training rats to discriminate the relative intensity of sounds at the two ears at various absolute levels. These experiments revealed the existence of a psychophysical regularity, which we term time-intensity equivalence in discrimination (TIED), describing how reaction times change as a function of absolute level.

An effect of serotonergic stimulation on learning rates for rewards apparent after long intertrial intervals.

Serotonin has widespread, but computationally obscure, modulatory effects on learning and cognition. Here, we studied the impact of optogenetic stimulation of dorsal raphe serotonin neurons in mice performing a non-stationary, reward-driven decision-making task. Animals showed two distinct choice strategies.

Activation of serotonin neurons promotes active persistence in a probabilistic foraging task.

The neuromodulator serotonin (5-HT) has been implicated in a variety of functions that involve patience or impulse control. Many of these effects are consistent with a long-standing theory that 5-HT promotes behavioral inhibition, a motivational bias favoring passive over active behaviors. To further test this idea, we studied the impact of 5-HT in a probabilistic foraging task, in which mice must learn the statistics of the environment and infer when to leave a depleted foraging site for the next.

Stereotaxic Adeno-associated Virus Injection and Cannula Implantation in the Dorsal Raphe Nucleus of Mice.

Optogenetic methods are now widespread in neuroscience research. Here we present a detailed surgical procedure to inject adeno-associated viruses and implant optic fiber cannulas in the dorsal raphe nucleus (DRN) of living mice. Combined with transgenic mouse lines, this protocol allows specific targeting of serotonin-producing neurons in the brain.

Distinct Sources of Deterministic and Stochastic Components of Action Timing Decisions in Rodent Frontal Cortex.

The selection and timing of actions are subject to determinate influences such as sensory cues and internal state as well as to effectively stochastic variability. Although stochastic choice mechanisms are assumed by many theoretical models, their origin and mechanisms remain poorly understood. Here we investigated this issue by studying how neural circuits in the frontal cortex determine action timing in rats performing a waiting task.

Activity patterns of serotonin neurons underlying cognitive flexibility.

Serotonin is implicated in mood and affective disorders. However, growing evidence suggests that a core endogenous role is to promote flexible adaptation to changes in the causal structure of the environment, through behavioral inhibition and enhanced plasticity. We used long-term photometric recordings in mice to study a population of dorsal raphe serotonin neurons, whose activity we could link to normal reversal learning using pharmacogenetics.

Transient inhibition and long-term facilitation of locomotion by phasic optogenetic activation of serotonin neurons.

Serotonin (5-HT) is associated with mood and motivation but the function of endogenous 5-HT remains controversial. Here, we studied the impact of phasic optogenetic activation of 5-HT neurons in mice over time scales from seconds to weeks. We found that activating dorsal raphe nucleus (DRN) 5-HT neurons induced a strong suppression of spontaneous locomotor behavior in the open field with rapid kinetics (onset ≤1 s).