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This study focuses on understanding visual coding in multiple brain areas and its implications for neural processing in the visual system. It highlights the use of simultaneous recordings of large neuronal populations to investigate how visual information is encoded and processed in the brain. By studying the activity of multiple brain areas, the paper aims to uncover the mechanisms underlying brain-wide visual perception and provide insights into the neural basis of visual processing. The findings of this research contribute to the broader field of neuroscience and have implications for understanding visual disorders and developing therapeutic interventions

Abstract 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a potent classical psychedelic known to induce changes in locomotion, behaviour, and sleep in rodents. However, there is limited knowledge regarding its acute neurophysiological effects. Local field potentials (LFPs) are commonly used as a proxy for neural activity, but previous studies investigating psychedelics have been hindered by confounding effects of behavioural changes and anaesthesia, which alter these signals. To address this gap, we investigated acute LFP changes in the hippocampus (HP) and medial prefrontal cortex (mPFC) of freely behaving rats, following 5-MeO-DMT administration. 5-MeO-DMT led to an increase of delta power and a decrease of theta power in the HP LFPs, which could not be accounted for by changes in locomotion. Furthermore, we observed a dose-dependent reduction in slow (20–50 Hz) and mid (50–100 Hz) gamma power, as well as in theta phase modulation, even after controlling for the effects of speed and theta power. State map analysis of the spectral profile of waking behaviour induced by 5-MeO-DMT revealed similarities to electrophysiological states observed during slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. Our findings suggest that the psychoactive effects of classical psychedelics are associated with the integration of waking behaviours with sleep-like spectral patterns in LFPs.

Schizophrenia (SZ) is a severe mental disorder associated with a variety of linguistic deficits, and recently it has been suggested that these deficits are caused by an underlying impairment in the ability to build complex syntactic structures and complex semantic relations. Aiming at contributing to determining the specific linguistic profile of SZ, we investigated the usage of pronominal subjects and sentence types in two corpora of oral dream and waking reports produced by speakers with SZ and participants without SZ (NSZ), both native speakers of Brazilian Portuguese. Narratives of 40 adult participants (20 SZ, and 20 NSZ-sample 1), and narratives of 31 teenage participants (11 SZ undergoing first psychotic episode, and 20 NSZ-sample 2) were annotated and statistically analyzed. Overall, narratives of speakers with SZ presented significantly higher rates of matrix sentences, null pronouns-particularly null 3Person referential pronouns-and lower rates of non-anomalous truncated sentences. The high rate of matrix sentences correlated significantly with the total PANSS scores, suggesting an association between the overuse of simple sentences and SZ symptoms in general. In contrast, the high rate of null pronouns correlated significantly with positive PANSS scores, suggesting an association between the overuse of null pronominal forms and the positive symptoms of SZ. Finally, a cross-group analysis between samples 1 and 2 indicated a higher degree of grammatical impairment in speakers with multiple psychotic episodes. Altogether, the results strengthen the notion that deficits at the pronominal and sentential levels constitute a cross-cultural linguistic marker of SZ.

The ‘day residue’ - the presence of waking memories into dreams - is a century-old concept that remains controversial in neuroscience. Even at the psychological level, it remains unclear how waking imagery cedes into dreams. Are visual and affective residues enhanced, modified, or erased at sleep onset? Are they linked, or dissociated? What are the neural correlates of these transformations? To address these questions we combined quantitative semantics, sleep EEG markers, visual stimulation, and multiple awakenings to investigate visual and affect residues in hypnagogic imagery at sleep onset. Healthy adults were repeatedly stimulated with an affective image, allowed to sleep and awoken seconds to minutes later, during waking (WK), N1 or N2 sleep stages. ‘Image Residue’ was objectively defined as the formal semantic similarity between oral reports describing the last image visualized before closing the eyes (‘ground image’), and oral reports of subsequent visual imagery (‘hypnagogic imagery). Similarly, ‘Affect Residue’ measured the proximity of affective valences between ‘ground image’ and ‘hypnagogic imagery’. We then compared these grounded measures of two distinct aspects of the ‘day residue’, calculated within participants, to randomly generated values calculated across participants. The results show that Image Residue persisted throughout the transition to sleep, increasing during N1 in proportion to the time spent in this stage. In contrast, the Affect Residue was gradually neutralized as sleep progressed, decreasing in proportion to the time spent in N1 and reaching a minimum during N2. EEG power in the theta band (4.5-6.5 Hz) was inversely correlated with the Image Residue during N1. The results show that the visual and affective aspects of the ‘day residue’ in hypnagogic imagery diverge at sleep onset, possibly decoupling visual contents from strong negative emotions, in association with increased theta rhythm.

Abstract Hippocampal (HPC) theta oscillation during post-training rapid eye movement (REM) sleep supports spatial learning. Theta also modulates neuronal and oscillatory activity in the retrosplenial cortex (RSC) during REM sleep. To investigate the relevance of theta-driven interaction between these two regions to memory consolidation, we computed the Granger causality within theta range on electrophysiological data recorded in freely behaving rats during REM sleep, both before and after contextual fear conditioning. We found a training-induced modulation of causality between HPC and RSC that was correlated with memory retrieval 24 h later. Retrieval was proportional to the change in the relative influence RSC exerted upon HPC theta oscillation. Importantly, causality peaked during theta acceleration, in synchrony with phasic REM sleep. Altogether, these results support a role for phasic REM sleep in hippocampo-cortical memory consolidation and suggest that causality modulation between RSC and HPC during REM sleep plays a functional role in that phenomenon.

Abstract Studies using zebrafish (Danio rerio) in neuro-behavioural research are growing. Measuring fish behavior by computational methods is one of the most efficient ways to avoid human bias in experimental analyses, extending them to various approaches. Sometimes, thorough analyses are difficult to do, as fish can behave unpredictably during an experimental strategy. However, the analyses can be implemented in an automated way, using an online strategy and video processing for a complete assessment of the zebrafish behavior, based on the detection and tracking of fish during an activity. Here, a fully automatic conditioning and detailed analysis of zebrafish behavior is presented. Microcontrolled components were used to control the delivery of visual and sound stimuli, in addition to the concise amounts of food after conditioned stimuli for adult zebrafish groups in a conventional tank. The images were captured and processed for automatic detection of the fish, and the training of the fish was done in two evaluation strategies: simple and complex. In simple conditioning, the zebrafish showed significant responses from the second attempt, learning that the conditioned stimulus was a predictor of food presentation in a specific space of the tank, where the food was dumped. When the fish were subjected to two stimuli for decision-making in the food reward, the zebrafish obtained better responses to red light stimuli in relation to vibration. The behavior change was clear in stimulated fish in relation to the control group, thus, the distances traveled and the speed were greater, while the polarization was lower in stimulated fish. This automated system allows for the conditioning and assessment of zebrafish behavior online, with greater stability in experiments, and in the analysis of the behavior of individual fish or fish schools, including learning and memory studies.

Abstract Fish show rapid movements in various behavioral activities or associated with the presence of food. However, in periods of rapid movement, the rate at which occlusion occurs among the fish is quite high, causing inconsistency in the detection and tracking of fish, hindering the fish's identity and behavioral trajectory over a long period of time. Although some algorithms have been proposed to solve these problems, most of their applications were made in groups of fish that swim in shallow water and calm behavior, with few sudden movements. To solve these problems, a convolutional network of object recognition, YOLOv2, was used to delimit the region of the fish heads to optimize individual fish detection. In the tracking phase, the Kalman filter was used to estimate the best state of the fish's head position in each frame and, subsequently, the trajectories of each fish were connected among the frames. The results of the algorithm show adequate performances in the trajectories of groups of zebrafish that exhibited rapid movements.

Non-semantic word graphs obtained from oral reports are useful to describe cognitive decline in psychiatric conditions such as Schizophrenia, as well as education-related gains in discourse structure during typical development. Here we provide non-semantic word graph attributes of texts spanning approximately 4500 years of history, and pre-literate Amerindian oral narratives. The dataset assessed comprises 707 literary texts representative of 9 different Afro-Eurasian traditions (Syro-Mesopotamian, Egyptian, Hinduist, Persian, Judeo-Christian, Greek-Roman, Medieval, Modern and Contemporary), and Amerindian narratives (N = 39) obtained from a single ethnic group from South America (Kalapalo, N = 18), or from a mixed ethnic group from South, Central and North America (non-Kalapalo, N = 21). The present article provides detailed information about each text or narrative, including measurements of four graph attributes of interest: number of nodes (lexical diversity), repeated edges (short-range recurrence), largest strongly connected component (long-range recurrence), and average shortest path (graph length).

Summary: We have recently used randomized controlled trials to examine the impact of a short neuroscience-informed causal intervention using a targeted training to inhibit a deeply rooted visual mechanism (mirror invariance) that hinders literacy acquisition, combined with post-training sleep (for learning consolidation). Using this training protocol, we have shown unprecedented improvements in visual perception of letters, writing, and a two-fold increase in reading fluency in first graders. Here, we describe this ecologically valid school-based intervention protocol to probe inhibition of mirror invariance for letters, including the detailed training instructions, post-training sleep consolidation, as well as practical tips and potential adaptations to different school sizes.For complete details on the use and execution of this protocol, please refer to Torres et al., (2021).

Summary: Previous observations suggest the existence of ‘Active sleep’ in cephalopods. To investigate in detail the behavioral structure of cephalopod sleep, we video-recorded four adult specimens of Octopus insularis and quantified their distinct states and transitions. Changes in skin color and texture and movements of eyes and mantle were assessed using automated image processing tools, and arousal threshold was measured using sensory stimulation. Two distinct states unresponsive to stimulation occurred in tandem. The first was a ‘Quiet sleep’ state with uniformly pale skin, closed pupils, and long episode durations (median 415.2 s). The second was an ‘Active sleep’ state with dynamic skin patterns of color and texture, rapid eye movements, and short episode durations (median 40.8 s). ‘Active sleep’ was periodic (60% of recurrences between 26 and 39 min) and occurred mostly after ‘Quiet sleep’ (82% of transitions). These results suggest that cephalopods have an ultradian sleep cycle analogous to that of amniotes.

Lucid dreaming (LD) began to be scientifically studied in the last century, but various religions have highlighted the importance of LD in their doctrines for a much longer period. Hindus’ manuscripts dating back over 2,000 years ago, for example, divide consciousness in waking, dreaming (including LD), and deep sleep. In the Buddhist tradition, Tibetan monks have been practicing the “Dream Yoga,” a meditation technique that instructs dreamers to recognize the dream, overcome all fears when lucid, and control the oneiric content. In the Islamic sacred scriptures, LD is regarded as a mental state of great value, and a special way for the initiated to reach mystical experiences. The Christian theologian Augustine of Hippo (354–430 AD) mentions LD as a kind of preview of the afterlife, when the soul separates from the body. In the nineteenth century, some branches of the Spiritism religion argue that LD precedes out-of-body experiences during sleep. Here we reviewed how these religions interpret dreams, LD and other conscious states during sleep. We observed that while Abrahamic monotheisms (Judaism, Christianity, and Islam) recognize dreams as a way to communicate with God to understand the present and predict the future, the traditional Indian religions (Buddhism and Hinduism) are more engaged in cultivating self-awareness, thus developed specific techniques to induce LD and witnessing sleep. Teachings from religious traditions around the world offer important insights for scientific researchers today who want to understand the full range of LD phenomenology as it has emerged through history.

Dream reports collected after rapid eye movement sleep (REM) awakenings are, on average, longer, more vivid, bizarre, emotional and story-like compared to those collected after non-REM. However, a comparison of the word-to-word structural organization of dream reports is lacking, and traditional measures that distinguish REM and non-REM dreaming may be confounded by report length. This problem is amenable to the analysis of dream reports as non-semantic directed word graphs, which provide a structural assessment of oral reports, while controlling for individual differences in verbosity. Against this background, the present study had two main aims: Firstly, to investigate differences in graph structure between REM and non-REM dream reports, and secondly, to evaluate how non-semantic directed word graph analysis compares to the widely used measure of report length in dream analysis. To do this, we analyzed a set of 133 dream reports obtained from 20 participants in controlled laboratory awakenings from REM and N2 sleep. We found that: (1) graphs from REM sleep possess a larger connectedness compared to those from N2; (2) measures of graph structure can predict ratings of dream complexity, where increases in connectedness and decreases in randomness are observed in relation to increasing dream report complexity; and (3) measures of the Largest Connected Component of a graph can improve a model containing report length in predicting sleep stage and dream report complexity. These results indicate that dream reports sampled after REM awakening have on average a larger connectedness compared to those sampled after N2 (i.e. words recur with a longer range), a difference which appears to be related to underlying differences in dream complexity. Altogether, graph analysis represents a promising method for dream research, due to its automated nature and potential to complement report length in dream analysis.

The current global threat brought on by the Covid-19 pandemic has led to widespread social isolation, posing new challenges in dealing with metal suffering related to social distancing, and in quickly learning new social habits intended to prevent contagion. Neuroscience and psychology agree that dreaming helps people to cope with negative emotions and to learn from experience, but can dreaming effectively reveal mental suffering and changes in social behavior? To address this question, we applied natural language processing tools to study 239 dream reports by 67 individuals, made either before the Covid-19 outbreak or during the months of March and April, 2020, when lockdown was imposed in Brazil following the WHO's declaration of the pandemic. Pandemic dreams showed a higher proportion of anger and sadness words, and higher average semantic similarities to the terms "contamination" and "cleanness". These features seem to be associated with mental suffering linked to social isolation, as they explained 40% of the variance in the PANSS negative subscale related to socialization (p = 0.0088). These results corroborate the hypothesis that pandemic dreams reflect mental suffering, fear of contagion, and important changes in daily habits that directly impact socialization.

Diagnosis: Early signs of speech problems indicative of thought disorder Abnormal speech in someone showing early signs of psychosis can help doctors diagnose schizophrenia and its ‘negative’ symptoms. Natália Mota from the Federal University of Rio Grande do Norte, Brazil, and colleagues asked 21 people undergoing first clinical contact for recent-onset psychosis and 21 healthy controls to recall a dream or recent memory. They then analyzed the structure of the participants’ verbal reports using a mathematical technique. The patients were followed up during 6 months to establish a more formal diagnosis. The researchers found that those later diagnosed with schizophrenia exhibited more disorganized speech (almost random in structure) at the initial doctor’s visit than those later diagnosed with bipolar disorder. Less connected speech among people with schizophrenia was also indicative of more severe negative symptoms such as blunted emotions and lack of motivation.

Background Historically, the primary sensory areas of the cerebral cortex have been exclusively associated with the processing of a single sensory modality. Yet the presence of tactile responses in the primary visual (V1) cortex has challenged this view, leading to the notion that primary sensory areas engage in cross-modal processing, and that the associated circuitry is modifiable by such activity. To explore this notion, here we assessed whether the exploration of novel objects in the dark induces the activation of plasticity markers in the V1 cortex of rats. Methods Adult rats were allowed to freely explore for 20 min a completely dark box with four novel objects of different shapes and textures. Animals were euthanized either 1 (n = 5) or 3 h (n = 5) after exploration. A control group (n = 5) was placed for 20 min in the same environment, but without the objects. Frontal sections of the brains were submitted to immunohistochemistry to measure protein levels of egr-1 and c-fos, and phosphorylated calcium-dependent kinase (pCaKMII) in V1 cortex. Results The amount of neurons labeled with monoclonal antibodies against c-fos, egr-1 or pCaKMII increased significantly in V1 cortex after one hour of exploration in the dark. Three hours after exploration, the number of labeled neurons decreased to basal levels. Conclusions Our results suggest that non-visual exploration induces the activation of immediate-early genes in V1 cortex, which is suggestive of cross-modal processing in this area. Besides, the increase in the number of neurons labeled with pCaKMII may signal a condition promoting synaptic plasticity.

Dopamine release and phase-amplitude cross-frequency coupling (CFC) have independently been implicated in prefrontal cortex (PFC) functioning. To causally investigate whether dopamine release affects phase-amplitude comodulation between different frequencies in local field potentials (LFP) recorded from the medial PFC (mPFC) of behaving rats, we used RuBiDopa, a light-sensitive caged compound that releases the neurotransmitter dopamine when irradiated with visible light. LFP power did not change in any frequency band after the application of light-uncaged dopamine, but significantly strengthened phase-amplitude comodulation between delta and gamma oscillations. Saline did not exert significant changes, while injections of dopamine and RuBiDopa produced a slow increase in comodulation for several minutes after the injection. The results show that dopamine release in the medial PFC shifts phase-amplitude comodulation from theta-gamma to delta-gamma. Although being preliminary results due to the limitation of the low number of animals present in this study, our findings suggest that dopamine-mediated modification of the frequencies involved in comodulation could be a mechanism by which this neurotransmitter regulates functioning in mPFC.

O presente estudo avalia se o modo como acessamos as palavras é influenciado pela estrutura do léxico; mais especificamente, se há diferenças na forma como reconhecemos palavras simples e compostas do Português Brasileiro (PB). Para isto, aplicamos dois testes de acesso lexical a 80 participantes para determinar (i) se há diferenças nos tempos de reação e acurácia de resposta entre palavras simples e compostas, e (ii) se essas diferenças se correlacionam com a frequência de uso dessas palavras. Os resultados do experimento 1 fornecem evidências para ocorrências de decomposição no reconhecimento de palavras compostas do PB. No entanto, as latências de resposta das palavras de altas frequências dos experimentos 1 e 2 confirmam as predições de modelos de listagem plena. Para explicar esses resultados sugerimos um mecanismo de acesso lexical em rota dupla, em que cada tipo de palavra é acessado mais rapidamente dependendo da sua frequência e de propriedades morfológicas.

No encontro entre matemática, física, química, biologia, psicologias, filosofia e artes, as neurociências fascinam o público pela possibilidade de compreensão dos mecanismos das emoções, pensamentos e ações, doenças e loucuras, aprendizado e esquecimento, sonhos e imaginação, fenômenos que nos definem e constituem. Como interpretar as novas descobertas das neurociências? O presente artigo aborda alguns tópicos de amplo interesse social: o envelhecimento, a educação, as drogas, o retorno científico à psicanálise e o problema da consciência.The neurosciences are at the confluence of mathematics, physics, chemistry, biology, psychology, philosophy, and the arts. They fascinate the general public due to the possibility of understanding the mechanisms of emotions, thoughts and actions, disease and madness, learning and forgetting, dreams and imagination, phenomena that define and conform us. How to interpret the new findings in neuroscience? This article discusses some topics of broad social interest: aging, education, drugs, the scientific return to psychoanalysis and the problem of consciousness.

Automatic classification of vocalization type could potentially become a useful tool for acoustic the monitoring of captive colonies of highly vocal primates. However, for classification to be useful in practice, a reliable algorithm that can be successfully trained on small datasets is necessary. In this work, we consider seven different classification algorithms with the goal of finding a robust classifier that can be successfully trained on small datasets. We found good classification performance (accuracy > 0.83 and F1-score > 0.84) using the Optimum Path Forest classifier. Dataset and algorithms are made publicly available.

Sleep is critical for hippocampus-dependent memory consolidation. However, the underlying mechanisms of synaptic plasticity are poorly understood. The central controversy is on whether long-term potentiation (LTP) takes a role during sleep and which would be its specific effect on memory. To address this question, we used immunohistochemistry to measure phosphorylation of Ca2+/calmodulin-dependent protein kinase II (pCaMKIIα) in the rat hippocampus immediately after specific sleep-wake states were interrupted. Control animals not exposed to novel objects during waking (WK) showed stable pCaMKIIα levels across the sleep-wake cycle, but animals exposed to novel objects showed a decrease during subsequent slow-wave sleep (SWS) followed by a rebound during rapid-eye-movement sleep (REM). The levels of pCaMKIIα during REM were proportional to cortical spindles near SWS/REM transitions. Based on these results, we modeled sleep-dependent LTP on a network of fully connected excitatory neurons fed with spikes recorded from the rat hippocampus across WK, SWS and REM. Sleep without LTP orderly rescaled synaptic weights to a narrow range of intermediate values. In contrast, LTP triggered near the SWS/REM transition led to marked swaps in synaptic weight ranking. To better understand the interaction between rescaling and restructuring during sleep, we implemented synaptic homeostasis and embossing in a detailed hippocampal-cortical model with both excitatory and inhibitory neurons. Synaptic homeostasis was implemented by weakening potentiation and strengthening depression, while synaptic embossing was simulated by evoking LTP on selected synapses. We observed that synaptic homeostasis facilitates controlled synaptic restructuring. The results imply a mechanism for a cognitive synergy between SWS and REM, and suggest that LTP at the SWS/REM transition critically influences the effect of sleep: Its lack determines synaptic homeostasis, its presence causes synaptic restructuring.

The experiences induced by psychedelics share a wide variety of subjective features, related to the complex changes in perception and cognition induced by this class of drugs. A remarkable increase in introspection is at the core of these altered states of consciousness. Self-oriented mental activity has been consistently linked to the Default Mode Network (DMN), a set of brain regions more active during rest than during the execution of a goal-directed task. Here we used fMRI technique to inspect the DMN during the psychedelic state induced by Ayahuasca in ten experienced subjects. Ayahuasca is a potion traditionally used by Amazonian Amerindians composed by a mixture of compounds that increase monoaminergic transmission. In particular, we examined whether Ayahuasca changes the activity and connectivity of the DMN and the connection between the DMN and the task-positive network (TPN). Ayahuasca caused a significant decrease in activity through most parts of the DMN, including its most consistent hubs: the Posterior Cingulate Cortex (PCC)/Precuneus and the medial Prefrontal Cortex (mPFC). Functional connectivity within the PCC/Precuneus decreased after Ayahuasca intake. No significant change was observed in the DMN-TPN orthogonality. Altogether, our results support the notion that the altered state of consciousness induced by Ayahuasca, like those induced by psilocybin (another serotonergic psychedelic), meditation and sleep, is linked to the modulation of the activity and the connectivity of the DMN.

The power-law size distributions obtained experimentally for neuronal avalanches are an important evidence of criticality in the brain. This evidence is supported by the fact that a critical branching process exhibits the same exponent [Formula: see text]. Models at criticality have been employed to mimic avalanche propagation and explain the statistics observed experimentally. However, a crucial aspect of neuronal recordings has been almost completely neglected in the models: undersampling. While in a typical multielectrode array hundreds of neurons are recorded, in the same area of neuronal tissue tens of thousands of neurons can be found. Here we investigate the consequences of undersampling in models with three different topologies (two-dimensional, small-world and random network) and three different dynamical regimes (subcritical, critical and supercritical). We found that undersampling modifies avalanche size distributions, extinguishing the power laws observed in critical systems. Distributions from subcritical systems are also modified, but the shape of the undersampled distributions is more similar to that of a fully sampled system. Undersampled supercritical systems can recover the general characteristics of the fully sampled version, provided that enough neurons are measured. Undersampling in two-dimensional and small-world networks leads to similar effects, while the random network is insensitive to sampling density due to the lack of a well-defined neighborhood. We conjecture that neuronal avalanches recorded from local field potentials avoid undersampling effects due to the nature of this signal, but the same does not hold for spike avalanches. We conclude that undersampled branching-process-like models in these topologies fail to reproduce the statistics of spike avalanches.

BackgroundPsychosis has various causes, including mania and schizophrenia. Since the differential diagnosis of psychosis is exclusively based on subjective assessments of oral interviews with patients, an objective quantification of the speech disturbances that characterize mania and schizophrenia is in order. In principle, such quantification could be achieved by the analysis of speech graphs. A graph represents a network with nodes connected by edges; in speech graphs, nodes correspond to words and edges correspond to semantic and grammatical relationships.Methodology/principal findingsTo quantify speech differences related to psychosis, interviews with schizophrenics, manics and normal subjects were recorded and represented as graphs. Manics scored significantly higher than schizophrenics in ten graph measures. Psychopathological symptoms such as logorrhea, poor speech, and flight of thoughts were grasped by the analysis even when verbosity differences were discounted. Binary classifiers based on speech graph measures sorted schizophrenics from manics with up to 93.8% of sensitivity and 93.7% of specificity. In contrast, sorting based on the scores of two standard psychiatric scales (BPRS and PANSS) reached only 62.5% of sensitivity and specificity.Conclusions/significanceThe results demonstrate that alterations of the thought process manifested in the speech of psychotic patients can be objectively measured using graph-theoretical tools, developed to capture specific features of the normal and dysfunctional flow of thought, such as divergence and recurrence. The quantitative analysis of speech graphs is not redundant with standard psychometric scales but rather complementary, as it yields a very accurate sorting of schizophrenics and manics. Overall, the results point to automated psychiatric diagnosis based not on what is said, but on how it is said.

Norepinephrine (NE) is thought to play important roles in the consolidation and retrieval of long-term memories, but its role in the processing and memorization of complex acoustic signals used for vocal communication has yet to be determined. We have used a combination of gene expression analysis, electrophysiological recordings and pharmacological manipulations in zebra finches to examine the role of noradrenergic transmission in the brain's response to birdsong, a learned vocal behavior that shares important features with human speech. We show that noradrenergic transmission is required for both the expression of activity-dependent genes and the long-term maintenance of stimulus-specific electrophysiological adaptation that are induced in central auditory neurons by stimulation with birdsong. Specifically, we show that the caudomedial nidopallium (NCM), an area directly involved in the auditory processing and memorization of birdsong, receives strong noradrenergic innervation. Song-responsive neurons in this area express α-adrenergic receptors and are in close proximity to noradrenergic terminals. We further show that local α-adrenergic antagonism interferes with song-induced gene expression, without affecting spontaneous or evoked electrophysiological activity, thus dissociating the molecular and electrophysiological responses to song. Moreover, α-adrenergic antagonism disrupts the maintenance but not the acquisition of the adapted physiological state. We suggest that the noradrenergic system regulates long-term changes in song-responsive neurons by modulating the gene expression response that is associated with the electrophysiological activation triggered by song. We also suggest that this mechanism may be an important contributor to long-term auditory memories of learned vocalizations.

Multielectrodes have been used with great success to simultaneously record the activity of neuronal populations in awake, behaving animals. In particular, there is great promise in the use of this technique to allow the control of neuroprosthetic devices by human patients. However, it is crucial to fully characterize the tissue response to the chronic implants in animal models ahead of the initiation of human clinical trials. Here we evaluated the effects of unilateral multielectrode implants on the motor cortex of rats weekly recorded for 1-6 months using several histological methods to assess metabolic markers, inflammatory response, immediate-early gene (IEG) expression, cytoskeletal integrity and apoptotic profiles. We also investigated the correlations between each of these features and firing rates, to estimate the impact of post-implant time on neuronal recordings. Overall, limited neuronal loss and glial activation were observed on the implanted sites. Reactivity to enzymatic metabolic markers and IEG expression were not significantly different between implanted and non-implanted hemispheres. Multielectrode recordings remained viable for up to 6 months after implantation, and firing rates correlated well to the histochemical and immunohistochemical markers. Altogether, our results indicate that chronic tungsten multielectrode implants do not substantially alter the histological and functional integrity of target sites in the cerebral cortex.

Scale-invariant neuronal avalanches have been observed in cell cultures and slices as well as anesthetized and awake brains, suggesting that the brain operates near criticality, i.e. within a narrow margin between avalanche propagation and extinction. In theory, criticality provides many desirable features for the behaving brain, optimizing computational capabilities, information transmission, sensitivity to sensory stimuli and size of memory repertoires. However, a thorough characterization of neuronal avalanches in freely-behaving (FB) animals is still missing, thus raising doubts about their relevance for brain function.To address this issue, we employed chronically implanted multielectrode arrays (MEA) to record avalanches of action potentials (spikes) from the cerebral cortex and hippocampus of 14 rats, as they spontaneously traversed the wake-sleep cycle, explored novel objects or were subjected to anesthesia (AN). We then modeled spike avalanches to evaluate the impact of sparse MEA sampling on their statistics. We found that the size distribution of spike avalanches are well fit by lognormal distributions in FB animals, and by truncated power laws in the AN group. FB data surrogation markedly decreases the tail of the distribution, i.e. spike shuffling destroys the largest avalanches. The FB data are also characterized by multiple key features compatible with criticality in the temporal domain, such as 1/f spectra and long-term correlations as measured by detrended fluctuation analysis. These signatures are very stable across waking, slow-wave sleep and rapid-eye-movement sleep, but collapse during anesthesia. Likewise, waiting time distributions obey a single scaling function during all natural behavioral states, but not during anesthesia. Results are equivalent for neuronal ensembles recorded from visual and tactile areas of the cerebral cortex, as well as the hippocampus.Altogether, the data provide a comprehensive link between behavior and brain criticality, revealing a unique scale-invariant regime of spike avalanches across all major behaviors.

Long-term changes in dopaminergic signaling are thought to underlie the pathophysiology of a number of psychiatric disorders. Several conditions are associated with cognitive deficits such as disturbances in attention processes and learning and memory, suggesting that persistent changes in dopaminergic signaling may alter neural mechanisms underlying these processes. Dopamine transporter knockout (DAT-KO) mice exhibit a persistent five-fold increase in extracellular dopamine levels. Here, we demonstrate that DAT-KO mice display lower hippocampal theta oscillation frequencies during baseline periods of waking and rapid-eye movement sleep. These altered theta oscillations are not reversed via treatment with the antidopaminergic agent haloperidol. Thus, we propose that persistent hyperdopaminergia, together with secondary alterations in other neuromodulatory systems, results in lower frequency activity in neural systems responsible for various cognitive processes.

Episodic and spatial memories engage the hippocampus during acquisition but migrate to the cerebral cortex over time. We have recently proposed that the interplay between slow-wave (SWS) and rapid eye movement (REM) sleep propagates recent synaptic changes from the hippocampus to the cortex. To test this theory, we jointly assessed extracellular neuronal activity, local field potentials (LFP), and expression levels of plasticity-related immediate-early genes (IEG) arc and zif-268 in rats exposed to novel spatio-tactile experience. Post-experience firing rate increases were strongest in SWS and lasted much longer in the cortex (hours) than in the hippocampus (minutes). During REM sleep, firing rates showed strong temporal dependence across brain areas: cortical activation during experience predicted hippocampal activity in the first post-experience hour, while hippocampal activation during experience predicted cortical activity in the third post-experience hour. Four hours after experience, IEG expression was specifically upregulated during REM sleep in the cortex, but not in the hippocampus. Arc gene expression in the cortex was proportional to LFP amplitude in the spindle-range (10-14 Hz) but not to firing rates, as expected from signals more related to dendritic input than to somatic output. The results indicate that hippocampo-cortical activation during waking is followed by multiple waves of cortical plasticity as full sleep cycles recur. The absence of equivalent changes in the hippocampus may explain its mnemonic disengagement over time.

The discovery of experience-dependent brain reactivation during both slow-wave (SW) and rapid eye-movement (REM) sleep led to the notion that the consolidation of recently acquired memory traces requires neural replay during sleep. To date, however, several observations continue to undermine this hypothesis. To address some of these objections, we investigated the effects of a transient novel experience on the long-term evolution of ongoing neuronal activity in the rat forebrain. We observed that spatiotemporal patterns of neuronal ensemble activity originally produced by the tactile exploration of novel objects recurred for up to 48 h in the cerebral cortex, hippocampus, putamen, and thalamus. This novelty-induced recurrence was characterized by low but significant correlations values. Nearly identical results were found for neuronal activity sampled when animals were moving between objects without touching them. In contrast, negligible recurrence was observed for neuronal patterns obtained when animals explored a familiar environment. While the reverberation of past patterns of neuronal activity was strongest during SW sleep, waking was correlated with a decrease of neuronal reverberation. REM sleep showed more variable results across animals. In contrast with data from hippocampal place cells, we found no evidence of time compression or expansion of neuronal reverberation in any of the sampled forebrain areas. Our results indicate that persistent experience-dependent neuronal reverberation is a general property of multiple forebrain structures. It does not consist of an exact replay of previous activity, but instead it defines a mild and consistent bias towards salient neural ensemble firing patterns. These results are compatible with a slow and progressive process of memory consolidation, reflecting novelty-related neuronal ensemble relationships that seem to be context- rather than stimulus-specific. Based on our current and previous results, we propose that the two major phases of sleep play distinct and complementary roles in memory consolidation: pretranscriptional recall during SW sleep and transcriptional storage during REM sleep.

Laboratory evidence of a positive effect of sleep on declarative memory consolidation suggests that naps can be used to boost school learning in a scalable, low-cost manner. The few direct investigations of this hypothesis have so far upheld it, but departed from the naturalistic setting by testing non-curricular contents presented by experimenters instead of teachers. Furthermore, nap and non-nap groups were composed of different children. Here we assessed the effect of post-class naps on the retention of Science and History curricular contents presented by the regular class teacher to 24 students from 5th grade. Retention was repeatedly measured 3-4 days after content learning, with weekly group randomization over 6 consecutive weeks. Contents followed by long naps (>30 min), but not short naps (<30 min), were significantly more retained than contents followed by waking (Cohen's d = 0.7962). The results support the use of post-class morning naps to enhance formal education.

Objective: To conduct Brazil’s first clinical trial employing 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder (PTSD), given its high prevalence resulting from epidemic violence. Methods: Of 60 volunteers, four matched the inclusion & exclusion criteria. Three patients with PTSD secondary to sexual abuse (diagnosed by the Structured Clinical Interview for DSM-IV and the Clinician Administered PTSD Scale for DSMV-4 [CAPS 4]) completed enrollment and treatment, following a standardized Multidisciplinary Association for Psychedelic Studies protocol consisting of 15 weekly therapy sessions: three with orally administered MDMA with concurrent psychotherapy and music, spaced approximately 1 month apart. CAPS-4 scores two months after the final MDMA session were the primary outcome. Results: No serious adverse events occurred. The most frequent adverse events were somatic pains and anguish. CAPS-4 reductions were always greater than 25 points. The final scores were 61, 27, and 8, down from baseline scores of 90, 78, and 72, respectively. All reductions were greater than 30%, which is indicative of clinically significant improvement. Secondary outcomes included lower Beck Depressive Inventory scores and higher Post-Traumatic Growth Inventory and Global Assessment of Functioning scores. Conclusions: Considering the current limitations in safe and efficacious treatments for PTSD and recent studies abroad with larger patient samples, MDMA-assisted psychotherapy could become a viable treatment in Brazil. Clinical trial registration: RBR-6sq4c9