Preparing and selecting actions with neural populations: toward cortical circuit mechanisms

How the brain selects one action among multiple alternatives is a central question of neuroscience. An influential model is that action preparation and selection arise from subthreshold activation of the very neurons encoding the action. Recent work, however, shows a much greater diversity of decision-related and action-related signals coexisting with other signals in populations of motor and parietal cortical neurons. We discuss how such distributed signals might be decoded by biologically plausible mechanisms. We also discuss how neurons within cortical circuits might interact with each other during action selection and preparation and how recurrent network models can help to reveal dynamical principles underlying cortical computation.info:eu-repo/semantics/publishedVersio

A Defined Network of Fast-Spiking Interneurons in Orbitofrontal Cortex: Responses to Behavioral Contingencies and Ketamine Administration

Orbitofrontal cortex (OFC) is a region of prefrontal cortex implicated in the motivational control of behavior and in related abnormalities seen in psychosis and depression. It has been hypothesized that a critical mechanism in these disorders is the dysfunction of GABAergic interneurons that normally regulate prefrontal information processing. Here, we studied a subclass of interneurons isolated in rat OFC using extracellular waveform and spike train analysis. During performance of a goal-directed behavioral task, the firing of this class of putative fast-spiking (FS) interneurons showed robust temporal correlations indicative of a functionally coherent network. FS cell activity also co-varied with behavioral response latency, a key indicator of motivational state. Systemic administration of ketamine, a drug that can mimic psychosis, preferentially inhibited this cell class. Together, these results support the idea that OFC–FS interneurons form a critical link in the regulation of motivation by prefrontal circuits during normal and abnormal brain and behavioral states

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. Electrophysiological recordings from two regions necessary for this behavior, medial prefrontal cortex (mPFC) and secondary motor cortex (M2), revealed an unexpected functional dissociation. Both areas encoded deterministic biases in action timing, but only M2 neurons reflected stochastic trial-by-trial fluctuations. This differential coding was reflected in distinct timescales of neural dynamics in the two frontal cortical areas. These results suggest a two-stage model in which stochastic components of action timing decisions are injected by circuits downstream of those carrying deterministic bias signals.info:eu-repo/semantics/publishedVersio

The Functional Microarchitecture of the Mouse Barrel Cortex

Cortical maps, consisting of orderly arrangements of functional columns, are a hallmark of the organization of the cerebral cortex. However, the microorganization of cortical maps at the level of single neurons is not known, mainly because of the limitations of available mapping techniques. Here, we used bulk loading of Ca2+ indicators combined with two-photon microscopy to image the activity of multiple single neurons in layer (L) 2/3 of the mouse barrel cortex in vivo. We developed methods that reliably detect single action potentials in approximately half of the imaged neurons in L2/3. This allowed us to measure the spiking probability following whisker deflection and thus map the whisker selectivity for multiple neurons with known spatial relationships. At the level of neuronal populations, the whisker map varied smoothly across the surface of the cortex, within and between the barrels. However, the whisker selectivity of individual neurons recorded simultaneously differed greatly, even for nearest neighbors. Trial-to-trial correlations between pairs of neurons were high over distances spanning multiple cortical columns. Our data suggest that the response properties of individual neurons are shaped by highly specific subcolumnar circuits and the momentary intrinsic state of the neocortex

Optogenetic Recruitment of Dorsal Raphe Serotonergic Neurons Acutely Decreases Mechanosensory Responsivity in Behaving Mice

The inhibition of sensory responsivity is considered a core serotonin function, yet this hypothesis lacks direct support due to methodological obstacles. We adapted an optogenetic approach to induce acute, robust and specific firing of dorsal raphe serotonergic neurons. In vitro, the responsiveness of individual dorsal raphe serotonergic neurons to trains of light pulses varied with frequency and intensity as well as between cells, and the photostimulation protocol was therefore adjusted to maximize their overall output rate. In vivo, the photoactivation of dorsal raphe serotonergic neurons gave rise to a prominent light-evoked field response that displayed some sensitivity to a 5-HT1A agonist, consistent with autoreceptor inhibition of raphe neurons. In behaving mice, the photostimulation of dorsal raphe serotonergic neurons produced a rapid and reversible decrease in the animals' responses to plantar stimulation, providing a new level of evidence that serotonin gates sensory-driven responses.ERC 250334, 5-HT OptogeneticMSCA 220098info:eu-repo/semantics/publishedVersio

The mechanistic foundation of Weber’s law

[Abstract] 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. The TIED enables the mathematical specification of the computational basis of Weber's law, placing strict requirements on how stimulus intensity is encoded in the stochastic activity of sensory neurons and revealing that discriminative choices must be based on bounded exact accumulation of evidence. We further demonstrate that this mechanism is not only necessary for the TIED to hold but is also sufficient to provide a virtually complete quantitative description of the behavior of the rats

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. However, water restriction requires rigorous monitoring of animals' health and hydration status and can be challenging for some mice. We present an alternative that allows mice more control over their water intake: free home-cage access to water, made slightly sour by a small amount of citric acid (CA). In a previous study, rats with free access to CA water readily performed a behavioral task for water rewards, although completing fewer trials than under water restriction (Reinagel, 2018). We here extend this approach to mice and confirm its robustness across multiple laboratories. Mice reduced their intake of CA water while maintaining healthy weights. Continuous home-cage access to CA water only subtly impacted their willingness to perform a decision-making task, in which they were rewarded with sweetened water. When free CA water was used instead of water restriction only on weekends, learning and decision-making behavior were unaffected. CA water is thus a promising alternative to water restriction, allowing animals more control over their water intake without interfering with behavioral performance

Neural antecedents of self-initiated actions in secondary motor cortex

The neural origins of spontaneous or self-initiated actions are not well understood and their interpretation is controversial. To address these issues, we used a task in which rats decide when to abort waiting for a delayed tone. We recorded neurons in the secondary motor cortex (M2) and interpreted our findings in light of an integration-to-bound decision model. A first population of M2 neurons ramped to a constant threshold at rates proportional to waiting time, strongly resembling integrator output. A second population, which we propose provide input to the integrator, fired in sequences and showed trial-to-trial rate fluctuations correlated with waiting times. An integration model fit to these data also quantitatively predicted the observed inter-neuronal correlations. Together, these results reinforce the generality of the integration-to-bound model of decision-making. These models identify the initial intention to act as the moment of threshold crossing while explaining how antecedent subthreshold neural activity can influence an action without implying a decision.info:eu-repo/semantics/publishedVersio