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Biology subjects

Cruz, B. F.

Publications and source records attributed to Cruz, B. F..

6 recordsLinked to original sources

Mice dynamically adapt to opponents in competitive multi-player games

Competing for resources in dynamic social environments is fundamental for survival and requires continuous monitoring of both self and others to guide effective choices. Yet most of our understanding of value-based decision-making comes from studying individuals in isolation, leaving open key questions about how animals adapt their strategies during social competition. Here, we developed an ethologically relevant multi-player game in which freely moving mice made valuebased decisions in a competitive spatial foraging task. We found that mice integrated real-time spatial information about both themselves and their opponents to flexibly shift their preferences toward safer, low-payout options when appropriate. Analyses of mice behaviour and reinforcement learning agents revealed that these adaptations could not be explained by simple reward learning, but were instead consistent with optimal decision strategies guided by opponent features. Using a dynamical model of decision-making, we found that competition increased choice variability and sensitivity to initial conditions, generating testable predictions for future neural recordings and perturbations. Together, our findings reveal a fundamental mechanism for flexible competitive foraging and propose novel frameworks for quantitatively understanding value-based decision-making in fast-changing social environments.

neuroscience↗

hiPSC-derived astrocytes from individuals with schizophrenia promote alterations in phagocytosis and chemotaxis of microglial-like cells

Neuroinflammation, particularly astrocyte reactivity, is increasingly linked to schizophrenia (SCZ). Yet, the crosstalk between astrocytes and microglia in SCZ, especially under pro-inflammatory conditions, remains unclear. Here, we employed human induced-pluripotent stem cells to compare how astrocytes from five age-matched individuals with SCZ and five neurotypical controls, upon stimulation with TNF-, affected microglial biology. TNF-[a] stimulation of SCZ astrocytes, relative to their control counterparts, triggered increased mRNA expression of pro-inflammatory cytokines and CX3CL1. Interestingly, transcriptomic and gene set enrichment analyses revealed that reactive SCZ astrocytes promoted the downregulation of biological processes associated with immune cell proliferation and activation, phagocytosis and cell migration in induced microglial-like cells (iMGs). Under such conditions, iMGs assumed a dystrophic/senescent-like phenotype, which was associated with accelerated transcriptional aging. Functional validations showed that TNF-[a]-stimulated SCZ astrocytes promoted reduced synaptoneurosomes phagocytosis by iMGs. Interestingly, only reactive control astrocytes were capable to induce significant microglial migration in a CX3CR1-dependent manner, despite the greater CX3CL1 secretion by reactive SCZ astrocytes compared to their stimulated control counterparts. This was likely due to SCZ astrocytes triggered reduction in CX3CR1 plasma membrane levels in iMGs. Altogether, these findings suggest that astrocytes contribute to SCZ pathology by altering normal microglial function and inducing a dystrophic phenotype. Main pointsO_LISCZ astrocytes display an increased pro-inflammatory profile upon stimulation with TNF-. C_LIO_LIReactive SCZ astrocytes induce microglial-like cells to assume a dystrophic phenotype. C_LIO_LIReactive SCZ astrocytes secreted factors impair microglial-like cells synaptoneurosome phagocytosis and limit their migration. C_LI

neuroscience↗

A flexible fluid delivery system for rodent behavior experiments

Experimental behavioral neuroscience relies on the ability to deliver precise amounts of liquid volumes to animal subjects. Among others, it allows the progressive shaping of behavior through successive, automated, reinforcement, thus allowing training in more demanding behavioral tasks and the manipulation of variables that underlie the decision making process (e.g.: reward magnitude). Here we introduce a stepper-motor-based, fully integrated, open-source solution, that allows the reproducible delivery of small (<1 {micro}L) liquid volumes. The system can be controlled via software using the Harp protocol (e.g.: from Bonsai or Python interfaces), or directly through a low-level I/O interface. Both the control software and electronics are compatible with a wide variety of motor models and mechanical designs. However, we also provide schematics, and step-by-step assembly instructions, for the mechanical design used and characterized in this manuscript. We provide benchmarks of the full integrated system using a computer-vision method capable of measuring across-trial delivery of small volumes, an important metric when having behavior experiments in mind. Finally, we provide experimental validation of our system by employing it in a psychophysics rodent task, and during electrophysiological recordings.

bioengineering↗

High-Performance Wide-Band Open-Source System for Acoustic Stimulation

The design and characterization of a low-cost, open-source auditory delivery system to deliver high performance auditory stimuli is presented. The system includes a high-fidelity sound card and audio amplifier devices with low-latency and wide bandwidth targeted for behavioral neuroscience research. The characterization of the individual devices and the entire system is performed, providing a thorough audio characterization data for varying frequencies and sound levels. The system implements the open-source Harp protocol, enabling the hardware timestamping of devices and seamless synchronization with other Harp devices. Specifications table O_TBL View this table: org.highwire.dtl.DTLVardef@6ee37aorg.highwire.dtl.DTLVardef@186f38org.highwire.dtl.DTLVardef@2dee9corg.highwire.dtl.DTLVardef@18c7f5aorg.highwire.dtl.DTLVardef@fd28fa_HPS_FORMAT_FIGEXP M_TBL C_TBL

neuroscience↗

Dopamine neurons encode a multidimensional probabilistic map of future reward

Learning to predict rewards is a fundamental driver of adaptive behavior. Midbrain dopamine neurons (DANs) play a key role in such learning by signaling reward prediction errors (RPEs) that teach recipient circuits about expected rewards given current circumstances and actions. However, the algorithm that DANs are thought to provide a substrate for, temporal difference (TD) reinforcement learning (RL), learns the mean of temporally discounted expected future rewards, discarding useful information concerning experienced distributions of reward amounts and delays. Here we present time-magnitude RL (TMRL), a multidimensional variant of distributional reinforcement learning that learns the joint distribution of future rewards over time and magnitude using an efficient code that adapts to environmental statistics. In addition, we discovered signatures of TMRL-like computations in the activity of optogenetically identified DANs in mice during a classical conditioning task. Specifically, we found significant diversity in both temporal discounting and tuning for the magnitude of rewards across DANs, features that allow the computation of a two dimensional, probabilistic map of future rewards from just 450ms of neural activity recorded from a population of DANs in response to a reward-predictive cue. In addition, reward time predictions derived from this population code correlated with the timing of anticipatory behavior, suggesting the information is used to guide decisions regarding when to act. Finally, by simulating behavior in a foraging environment, we highlight benefits of access to a joint probability distribution of reward over time and magnitude in the face of dynamic reward landscapes and internal physiological need states. These findings demonstrate surprisingly rich probabilistic reward information that is learned and communicated to DANs, and suggest a simple, local-in-time extension of TD learning algorithms that explains how such information may be acquired and computed.

animal behavior and cognition↗

Dorsolateral striatal circuits support broadly opponent aspects of action suppression and production

Imbalance between action suppression and production characterizes several neurological disorders of the basal ganglia (BG)1. Relatedly, two major circuits of the BG, the direct and indirect pathways, are hypothesized to function in opposition, promoting and suppressing actions, respectively2. Yet activity of neurons initiating the two pathways, striatal direct (dMSNs) and indirect (iMSNs) medium spiny neurons, appears to be positively correlated around movement, apparently contradicting direct-indirect functional opponency3. Here we show that while coactivation occurs during movement, action suppression produces systematic features of functional opponency between the two pathways. First, suppression produced elevated iMSN activity and diminished dMSN activity in dorsolateral striatum of mice. Second, as the need to suppress movements to one or the other side of the body evolved over time, so too did the relative levels of activity in the two hemispheres, and in opposite patterns in the two pathways. Lastly, optogenetic inhibition of dMSNs, but not iMSNs, slowed movements without affecting their likelihood, whereas inhibition of iMSNs, but not dMSNs, disrupted whether and when mice suppressed or produced particular actions. These data demonstrate large-scale opponency in the activity of neurons that initiate the direct and indirect pathways of the BG, but suggest distinct action-related functions of each pathway. Specifically, the data support a novel model of sensorimotor striatum wherein the direct pathway appears to be necessary for augmenting generalized movement vigor, and the indirect pathway for the proactive suppression of specific behaviors.

neuroscience↗