Sequence learning is a ubiquitous facet of human and animal cognition. Here, using a common sequence reproduction task, we investigated whether and how the ordinal and relational structures linking consecutive elements are acquired by human adults, children, and macaque monkeys. While children and monkeys exhibited significantly lower precision than adults for spatial location and temporal order information, only monkeys appeared to exceedingly focus on the first item. Most importantly, only humans, regardless of age, spontaneously extracted the spatial relations between consecutive items and used a chunking strategy to compress sequences in working memory. Monkeys did not detect such relational structures, even after extensive training. Monkey behavior was captured by a conjunctive coding model, whereas a chunk-based conjunctive model explained more variance in humans. These age- and species-related differences are indicative of developmental and evolutionary mechanisms of sequence encoding and may provid...

Neuronal remodeling after brain injury is essential for functional recovery. After unilateral cortical lesion, axons from the intact cortex ectopically project to the denervated midbrain, but the molecular mechanisms remain largely unknown. To address this issue, we examined gene expression profiles in denervated and intact mouse midbrains after hemispherectomy at early developmental stages using mice of either sex, when ectopic contralateral projection occurs robustly. The analysis showed that various axon growth-related genes were upregulated in the denervated midbrain, and most of these genes are reportedly expressed by glial cells. To identify the underlying molecules, the receptors for candidate upregulated molecules were knocked out in layer 5 projection neurons in the intact cortex, using the CRISPR/Cas9-mediated method, and axonal projection from the knocked-out cortical neurons was examined after hemispherectomy. We found that the ectopic projection was significantly reduced when integrin subunit ...

Acquiring new memories is a multistage process. Numerous studies have convincingly demonstrated that initially acquired memories are labile and are stabilized only by later consolidation processes. These multiple phases of memory formation are known to involve modification of both cellular excitability and synaptic connectivity, which in turn change neuronal activity at both the single neuron and ensemble levels. However, the specific mapping between the known phases of memory and the changes in neuronal activity at different organizational levels—the single-neuron, population representations, and ensemble-state dynamics—remains unknown. Here we address this issue in the context of conditioned taste aversion learning by continuously tracking gustatory cortex neuronal taste responses in alert male and female rats during the 24 h following a taste–malaise pairing. We found that the progression of activity changes depends on the neuronal organizational level: whereas the population response changed continuous...

A long-standing question in systems neuroscience is to what extent task-relevant features of neocortical processing are localized or distributed. Coordinated activity across the neocortex has been recently shown to drive complex behavior in the mouse, while activity in selected areas is canonically associated with specific functions (e.g., movements in the case of the motor cortex). Reach-to-grasp (RtG) movements are known to be dependent on motor circuits of the neocortex; however, the global activity of the neocortex during these movements has been largely unexplored in the mouse. Here, we characterized, using wide-field calcium imaging, these neocortex-wide dynamics in mice of either sex engaging in an RtG task. We demonstrate that, beyond motor regions, several areas, such as the visual and the retrosplenial cortices, also increase their activity levels during successful RtGs, and homologous regions across the ipsilateral hemisphere are also involved. Functional connectivity among neocortical areas inc...

Peripheral nerves are divided into multiple branches leading to divergent synaptic targets. This poses a remarkable challenge for regenerating axons as they select their original trajectory at nerve branch-points. Despite implications for functional regeneration, the molecular mechanisms underlying target selectivity are not well characterized. Danio Rerio (zebrafish) motor nerves are composed of a ventral and a dorsal branch that diverge at a choice-point, and we have previously shown that regenerating axons faithfully select their original branch and targets. Here we identify robo2 as a key regulator of target-selective regeneration (sex of experimental subjects unknown). We demonstrate that robo2 function in regenerating axons is required and sufficient to drive target-selective regeneration, and that robo2 acts in response to glia located precisely where regenerating axons select the branch-specific trajectory to prevent and correct axonal errors. Combined, our results reveal a glia-derived mechanism t...

Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent side effect of widely used platinum-based anticancer agents. There are few predictable risk factors with which to identify susceptible patients. Effective preventive measures or treatments are not available. Here, we have used a model of CIPN in Drosophila melanogaster to identify genetic changes that confer resistance to cisplatin-induced neuronal damage but not in the rapidly dividing cells of the ovary. The Drosophila strain attP40 , used as a genetic background for the creation of RNAi lines, is resistant to cisplatin damage compared with the similar attP2 background strain. attP40 flies have reduced mRNA expression of ND-13A , a component of the mitochondria electron transport chain complex I. Reduction of ND-13A via neuron-specific RNAi leads to resistance to the dose-dependent climbing deficiencies and neuronal apoptosis observed in control flies. These flies are also resistant to acute oxidative stress, suggesting a mechanism for resi...

Omnipause neurons (OPNs) in the nucleus raphe interpositus have tonic activity while the eyes are stationary (“fixation”) but stop firing immediately before and during saccades. To locate the source of suppression, we analyzed synaptic inputs from the rostral and caudal superior colliculi (SCs) to OPNs by using intracellular recording and staining, and investigated pathways transmitting the inputs in anesthetized cats of both sexes. Electrophysiologically or morphologically identified OPNs received monosynaptic excitation from the rostral SCs with contralateral dominance, and received disynaptic inhibition from the caudal SCs with ipsilateral dominance. Cutting the tectoreticular tract transversely between the contralateral OPN and inhibitory burst neuron (IBN) regions eliminated inhibition from the caudal SCs, but not excitation from the rostral SCs in OPNs. In contrast, a midline section between IBN regions eliminated disynaptic inhibition in OPNs from the caudal SCs but did not affect the monosynaptic e...

Category learning, learning to sort a set of stimuli into categories or groups, can induce category biases in perception such that items in the same category are perceived as more similar than items from different categories. To what degree category bias develops when learning goals emphasize individuation of each stimulus and whether the bias emerges spontaneously during learning itself rather than in response to task demands is unclear. Here, we used functional MRI (fMRI) during encoding to test for category biases in neural representations of individual stimuli during learning. Human participants (males and females) encountered face-blend stimuli with unique first names and shared family names that indicated category membership. Participants were instructed to learn the full name for each face. Neural pattern classification and pattern similarity analyses were used to track category information in the brain. Results showed that stimulus category could be decoded during encoding across many frontal, pari...

People adjust their learning rate rationally according to local environmental statistics and calibrate such adjustments based on the broader statistical context. To date, no theory has captured the observed range of adaptive learning behaviors or the complexity of its neural correlates. Here, we attempt to do so using a neural network model that learns to map an internal context representation onto a behavioral response via supervised learning. The network shifts its internal context upon receiving supervised signals that are mismatched to its output, thereby changing the “state” to which feedback is associated. A key feature of the model is that such state transitions can either increase learning or decrease learning depending on the duration over which the new state is maintained. Sustained state transitions that occur after changepoints facilitate faster learning and mimic network reset phenomena observed in the brain during rapid learning. In contrast, state transitions after one-off outlier events are...

The understanding of the electrophysiological properties of the subthalamic nucleus (STN) neurons is crucial since it represents the main target of deep brain stimulation for the treatment of Parkinson’s Disease and obsessive compulsive disorders. The study of its non-motor properties could shed light on the cognitive and motivational alterations possibly encountered after stimulation. In this study, we recorded the activity of STN neurons in two male behaving monkeys ( Macaca mulatta ) while they performed a visuomotor motivational task in which visual cues indicated which amount of force was required to obtain which amount of reward. Our results evidenced force- and reward-modulated neurons. After the occurrence of the visual stimuli, the force-modulated neurons mainly fired when a high effort was required. Differently, the activity of the population of reward-modulated neurons encoded the motivational value of the stimuli. This population consisted of neurons increasing or decreasing their activity acco...