Neurobehavioral Plasticity Research Articles

Neural acetylcholinesterase and monoamine oxidase deregulation during streptozotocin-induced behavioral, metabolic and redox modification in Nauphoeta cinerea.

Genetic and environmental factors have been linked with neurodegeneration, especially in the elderly. Yet, efforts to impede neurodegenerative processes have at best addressed symptoms instead of underlying pathologies. The gap in the understanding of neuro-behavioral plasticity is consistent from insects to mammals, and cockroaches have been proven to be effective models for studying the toxicity mechanisms of various chemicals. We therefore used head injection of 74 and 740 nmol STZ in Nauphoeta cinerea to elucidate the mechanisms of chemical-induced neurotoxicity, as STZ is known to cross the blood-brain barrier. Neurolocomotor assessment was carried out in a new environment, while head homogenate was used to estimate metabolic, neurotransmitter and redox activities, followed by RT-qPCR validation of relevant cellular signaling. STZ treatment reduced the distance and maximum speed travelled by cockroaches, and increased glucose levels while reducing triglyceride levels in neural tissues. The activity of neurotransmitter regulators - AChE and MAO was exacerbated, with concurrent upregulation of glucose sensing and signaling, and increased mRNA levels of redox regulators and inflammation-related genes. Consequently, STZ neurotoxicity is conserved in insects, with possible implications for using N. cinerea to target the multi-faceted mechanisms of neurodegeneration and test potential anti-neurodegenerative agents.

Persistent vocal learning in an aging open-ended learner reflected in neural FoxP2 expression

BackgroundMost vocal learning species exhibit an early critical period during which their vocal control neural circuitry facilitates the acquisition of new vocalizations. Some taxa, most notably humans and parrots, retain some degree of neurobehavioral plasticity throughout adulthood, but both the extent of this plasticity and the neurogenetic mechanisms underlying it remain unclear. Differential expression of the transcription factor FoxP2 in both songbird and parrot vocal control nuclei has been identified previously as a key pattern facilitating vocal learning. We hypothesize that the resilience of vocal learning to cognitive decline in open-ended learners will be reflected in an absence of age-related changes in neural FoxP2 expression. We tested this hypothesis in the budgerigar (Melopsittacus undulatus), a small gregarious parrot in which adults converge on shared call types in response to shifts in group membership. We formed novel flocks of 4 previously unfamiliar males belonging to the same age class, either “young adult” (6 mo − 1 year) or “older adult” (≥ 3 year), and then collected audio-recordings over a 20-day learning period to assess vocal learning ability. Following behavioral recording, immunohistochemistry was performed on collected neural tissue to measure FoxP2 protein expression in a parrot vocal learning center, the magnocellular nucleus of the medial striatum (MMSt), and its adjacent striatum.ResultsAlthough older adults show lower vocal diversity (i.e. repertoire size) and higher absolute levels of FoxP2 in the MMSt than young adults, we find similarly persistent downregulation of FoxP2 and equivalent vocal plasticity and vocal convergence in the two age cohorts. No relationship between individual variation in vocal learning measures and FoxP2 expression was detected.ConclusionsWe find neural evidence to support persistent vocal learning in the budgerigar, suggesting resilience to aging in the open-ended learning program of this species. The lack of a significant relationship between FoxP2 expression and individual variability in vocal learning performance suggests that other neurogenetic mechanisms could also regulate this complex behavior.

Unraveling the Influence of Litter Size, Maternal Care, Exercise, and Aging on Neurobehavioral Plasticity and Dentate Gyrus Microglia Dynamics in Male Rats.

This study explores the multifaceted influence of litter size, maternal care, exercise, and aging on rats' neurobehavioral plasticity and dentate gyrus microglia dynamics. Body weight evolution revealed a progressive increase until maturity, followed by a decline during aging, with larger litters exhibiting lower weights initially. Notably, exercised rats from smaller litters displayed higher body weights during the mature and aged stages. The dentate gyrus volumes showed no significant differences among groups, except for aged sedentary rats from smaller litters, which exhibited a reduction. Maternal care varied significantly based on litter size, with large litter dams showing lower frequencies of caregiving behaviors. Behavioral assays highlighted the detrimental impact of a sedentary lifestyle and reduced maternal care/large litters on spatial memory, mitigated by exercise in aged rats from smaller litters. The microglial dynamics in the layers of dentate gyrus revealed age-related changes modulated by litter size and exercise. Exercise interventions mitigated microgliosis associated with aging, particularly in aged rats. These findings underscore the complex interplay between early-life experiences, exercise, microglial dynamics, and neurobehavioral outcomes during aging.

Methylphenidate exposure in juvenile period elicits locomotion changes and anxiolytic-like behavior in adulthood: Evidence using zebrafish as a translational model

Methylphenidate (MPH) is a central nervous system stimulant that is mainly used for Attention-Deficit/Hyperactivity Disorder (ADHD). It is well known that there is a high rate of ADHD misdiagnosis, leading to a great number of neurotypical children chronically exposed to MPH in early periods of life. This increase raises concern about possible long-lasting effects of this exposure. We aimed to evaluate whether exposure to MPH during childhood might impact adult behavioral pattern. For this purpose, we used zebrafish as a translational model considering its robustness as experimental model and fast life cycle. Fish were exposed during juvenile period (from 30 to 60 post-natal day) at MPH therapeutic concentration (2 mg L−1), and behavioral tests were performed at fish adulthood (120 post-natal day). MPH provoked slight anxiolytic-like effects and hyperlocomotion, and no differences on sociability and cortisol levels were observed. Moreover, sex did not affect any of the parameters evaluated. These results demonstrate that early chronic exposure to MPH leads to neurobehavioral adaptations that persist into adulthood in zebrafish regardless of sex, suggesting that the misuse of MPH during childhood and adolescence can alter neurobehavioral plasticity and these alterations might persist until adulthood.

Cocaine-induced plasticity, motivation, and cue responsivity do not differ in obesity-prone vs obesity-resistant rats; implications for food addiction

RationaleCompared to obesity-resistant rats, obesity-prone rats consume more food, work harder to obtain food, show greater motivational responses to food-cues, and show greater striatal plasticity in response to eating sugary/fatty foods. Therefore, it is possible that obesity-prone rats may also be more sensitive to the motivational properties of cocaine and cocaine-paired cues, and to plasticity induced by cocaine.ObjectiveTo examine baseline differences in motivation for cocaine and effects of intermittent access (IntA) cocaine self-administration on cocaine motivation, neurobehavioral responsivity to cocaine-paired cues, and locomotor sensitization in male obesity-prone vs obesity-resistant rats.MethodsIntravenous cocaine self-administration was used to examine drug-taking and drug-seeking in males. Motivation for cocaine was measured using a within session threshold procedure. Cue-induced c-Fos expression in mesocorticolimbic regions was measured.ResultsDrug-taking and drug-seeking, cue-induced c-Fos, locomotor sensitization, and preferred level of cocaine consumption (Q0) were similar between obesity-prone and obesity-resistant groups. Maximal responding during demand testing (Rmax) was lower in obesity-prone rats. IntA experience enhanced motivation for cocaine (Pmax) in obesity-prone rats.ConclusionsThe results do not support robust inherent differences in motivation for cocaine, cue-induced cocaine seeking, or neurobehavioral plasticity induced by IntA in obesity-prone vs obesity-resistant rats. This contrasts with previously established differences seen for food and food cues in these populations and shows that inherent enhancements in motivation for food and food-paired cues do not necessarily transfer to drugs and drug-paired cues.

Effect of rate of intravenous cocaine infusion on psychomotor sensitization and striatal AMPAR expression in female rats

The speed at which addictive drugs reach the brain influences the magnitude of their effects and increases abuse liability. For example, in rats, fast rates of i.v. cocaine infusion (5 s) induce greater cocaine intake and self‐administration, and enhance psychomotor sensitization compared to slower infusion rates (90 s). Psychomotor sensitization is a behavioral manifestation of drug‐induced neural plasticity thought to underlie addiction. However, most rate of infusion (ROI) studies included only males and were limited to acute experimenter‐administered infusions. Furthermore, increases in cell‐surface expression of AMPA‐type glutamate receptors within the nucleus accumbens (NAc) are associated with psychomotor sensitization and enhanced cocaine‐seeking, but potential effects of ROI on NAc glutamate plasticity had not been examined. Therefore here, we examined psychomotor sensitization and glutamatergic plasticity in female Long‐Evans rats (N=22) given either fast (5 s, n=9) or slow (90 s, n=9) cocaine infusions (50 μl, 2.0 mg/kg i.v.) or saline infusions (5 s, n=2; 90 s, n=2). Rats were given one infusion per session, three sessions per week, for 8 total infusions. To examine effects on AMPAR expression, tissue from the NAc and dorsolateral striatal (DLS) will be collected after an additional 21 days of withdrawal. Briefly, tissue will be prepared using established BS3 crosslinking approaches, and surface expression of AMPAR subunits GluA1 and GluA2 will be examined. Psychomotor sensitization is typically quantified by measuring locomotion using automated beam break measures or by hand scoring behavior. However, beam break measures are inaccurate in small enclosures, and hand scoring is time‐consuming. Here, we developed a novel approach to measuring locomotion using DeepLabCut, a markerless pose estimation method. In pilot studies, tracking locomotion using this method provided reliable measures of locomotion that were comparable to hand‐scored videos. This approach also provided more detailed analysis of the entire time course (rather than using time sampling), and provided additional quantitative measures including velocity. In pilot studies, females in the fast infusion group showed locomotor sensitization, whereas rats in the slow infusion group did not. To our knowledge, this is the first demonstration that repeated slow infusions of cocaine do not produce sensitization, and suggests that although total drug exposure is identical, the speed of drug delivery strongly influences cocaine‐induced plasticity in females. Ongoing studies are being conducted to examine effects on glutamate plasticity. We predict that enhancements in AMPAR surface expression may occur selectively in the 5 s group, based on previous sensitization studies in males, but that this effect may be more pronounced in DLS than NAc. Together these data will reveal how varying pharmacokinetics influence cocaine‐induced neurobehavioral plasticity in females.

Adaptive functions of neurobehavioral plasticity in language learning and processing

AbstractThis article presents a large scope of issues on early and late language plasticity that increase our understanding of the neurobehavioral dynamics of change, the main property of the learning brain. In their pioneering work, Bates and Kuhl have convincingly demonstrated that plasticity is intrinsic to development. Bates has provided new data on the impressive recovery of language in children with focal brain injury, highlighting that both hemispheres support the early phases of this change, contrary to previous assumptions. The fundamental reorganization of the early phonemic system around the age of 8 months proposed by Kuhl, combining neural commitment and social abilities, has powerful cascading effects for subsequent word learning. Our developmental crosslinguistic research on online sentence processing in monolinguals and simultaneous bilinguals has revealed distinctive linguistic patterns of “cue cost”, a multifactorial concept relevant for capturing the microplasticity of the processing system. Whatever the language, the shift around the age of 9 towards the canonical adult pattern indicates an efficient adaptive processing occurring with a small delay in bilinguals. Most salient, from childhood, bilinguals exhibit specific cue cost patterns with interactions. In older French adults, cue cost variability is mediated by processing speed which preserves online syntactic abilities but reveals plasticity limits in Alzheimer’s patients.

Conflict between Threat Sensitivity and Sensation Seeking in the Adolescent Brain: Role of the Hippocampus, and Neurobehavioural Plasticity Induced by Pleasurable Early Enriched Experience.

Adolescence is characterized both by the exacerbation of the experience of anxiety, fear or threat, on one hand, and by increased reward seeking (reward sensitivity) and risk taking on the other hand. The rise of these apparently opposite processes, i.e., threat-related anxiety and reward-related sensation seeking, seems to stem from a relatively decreased top-down inhibition of amygdala and striatal circuits by regulatory systems (e.g., prefrontal cortex, hippocampus) that mature later. The present commentary article aims to discuss recent related literature and focusses on two main issues: (i) the septo-hippocampal system (in particular the ventral hippocampus) might be a crucial region for the regulation of approach–avoidance conflict and also for the selection of the most appropriate responses during adolescence, and (ii) developmental studies involving early-life pleasurable-enriched experience (as opposed to early-life adversity) might be a useful study paradigm in order to decipher whether neuroplasticity induced by such experiences (for example, in the hippocampus and associated circuitry) may lead to better top-down inhibition and more “balanced” adolescent responses to environmental demands.

Metabotropic Glutamate Receptor Trafficking and its Role in Drug-Induced Neurobehavioral Plasticity.

Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system that guides developmental and experience-dependent changes in many cellular substrates and brain circuits, through the process collectively referred to as neurobehavioral plasticity. Regulation of cell surface expression and membrane trafficking of glutamate receptors represents an important mechanism that assures optimal excitatory transmission, and at the same time, also allows for fine-tuning neuronal responses to glutamate. On the other hand, there is growing evidence implicating dysregulated glutamate receptor trafficking in the pathophysiology of several neuropsychiatric disorders. This review provides up-to-date information on the molecular determinants regulating trafficking and surface expression of metabotropic glutamate (mGlu) receptors in the rodent and human brain and discusses the role of mGluR trafficking in maladaptive synaptic plasticity produced by addictive drugs. As substantial evidence links glutamatergic dysfunction to the progression and the severity of drug addiction, advances in our understanding of mGluR trafficking may provide opportunities for the development of novel pharmacotherapies of addiction and other neuropsychiatric disorders.

Propofol but not dexmedetomidine produce locomotor sensitization via nitric oxide in rats

The abused potential of some anesthetics has been debated. Measurement of locomotor sensitization is a better way to detect the neurobehavioral plasticity of addiction. The present study aims to explore whether propofol and dexmedetomidine are capable of inducing locomotor sensitization. Male Wistar rats (250-300g) were the subjects (n= 8 for each group). Propofol (20 and 40mg/kg) and dexmedetomidine (2.5-20μg/kg) or saline were injected to rats intraperitoneally (IP), and their locomotor activities were recorded for 15min. Consequently, L-NAME (30 and 60mg/kg)-a nitric oxide (NO) inhibitory agent-was injected to rats 30min before propofol (40mg/kg) or saline injections, and the locomotor activity was recorded. The process was carried out for 13days, with 7 sessions applied every other day. Dexmedetomidine did not produce any significant locomotor sensitization. While propofol (20mg/kg) produced a significant locomotor sensitization in the last treatment session (day 13), at the higher dose, it prompted a significant locomotor sensitization from the 3rd treatment session. L-NAME blocked propofol-induced locomotor hyperactivity and sensitization significantly without producing any noteworthy changes on the locomotor activity during the testing period of 13days when administered alone. Our results suggest that propofol but not dexmedetomidine produced a significant locomotor sensitization via central nitrergic system. Dexmedetomidine may have a lesser psychostimulant type addictive potential than propofol. Sensitization development by propofol implies that this drug might be effective on the neuroadaptive processes associated with a stimulant type of dependence.

Neurobehavioral Effects of Restricted and Unpredictable Environmental Enrichment in Rats.

To study how motivational factors modulate experience-dependent neurobehavioral plasticity, we modify a protocol of environmental enrichment (EE) in rats. We assumed that the benefits derived from EE might vary according to the level of incentive salience attributed to it. To enhance the rewarding properties of EE, access to the EE cage varied randomly from 2 to 48 h for 30 days (REE). The REE group was enriched only 50% of the time and was compared to standard housing and continuous EE (CEE) groups. As behavioral readout, we analyzed the spontaneous activity and the ultrasonic vocalizations (USVs) within the EE cage weekly, and in the open field test at the end of the experiment. In the cage, REE increased the utilization of materials, physical activity, and the rate of appetitive USVs. In the OF, the CEE-induced enhancements in novelty habituation and social signaling were equaled by the REE. At the neural level, we measured the expression of genes related to neural plasticity and epigenetic regulations in different brain regions. In the dorsal striatum and hippocampus, REE upregulated the expression of the brain-derived neurotrophic factor, its tropomyosin kinase B receptor, and the DNA methyltransferase 3A. Altogether, our results suggest that the higher activity within the cage and the augmented incentive motivation provoked by the REE boosted its neurobehavioral effects equaling or surpassing those observed in the CEE condition. As constant exposures to treatments or stimulating environments are virtually impossible for humans, restricted EE protocols would have greater translational value than traditional ones.

Brain evoked potential Analysis of Effects of Popular Music Training on Adolescents' Cognitive Neurobehavioral Plasticity

In order to study the impact of pop music on cognitive neurobehavioral plasticity through the use of ERP technology, this study selected adolescents as the research target group, and studied the impact of music training on multiple cognitive functions, influence characteristics, brain structure and brain functional connection in different stages of popular music training through experimental analysis. The results indicated that pop music training not only enabled adolescents to acquire corresponding musical skill and music knowledge reserve, but also exerted a profound effect on adolescents' cerebral neural development. Meanwhile, the brain plasticity could also be improved, including the neural connection and information communication in the nervous system, making it possible for young people to exercise and develop multiple brain regions. The research results of this paper bear important reference significance for the application of pop music in adolescent education.

Increased brain glucocorticoid actions following social defeat in rats facilitates the long-term establishment of social subordination

Social rank is frequently established through aggressive encounters between new conspecifics. Despite increasing evidence suggesting that social rank is critical for the well-being of both humans and animals, knowledge about the factors influencing social rank remain scarce. Stress was previously shown to affect the establishment and maintenance of social hierarchies in rats. Likewise, increasing systemic corticosterone levels post-encounter in the emerging subordinate rat facilitates the long-term establishment of social subordination. Here, we investigated whether central corticosterone actions are sufficient to mediate this effect. Our data shows that, indeed, an intracerebroventricular corticosterone injection given to the emerging subordinate rat facilitates the long-term maintenance of the subordinate rank. Next, we attempted to identify a particular brain region in which enhancement of corticosterone actions could be sufficient to exert the facilitation of a long-term maintenance in the emerging subordinate brain. However, post-encounter administration of corticosterone into the basolateral amygdala, medial amygdala, lateral septum and the nucleus accumbens, brain regions selected for their implication in social rank establishment and emotional modulation of memory, did not affect long-term social subordination. Our study highlights the involvement of intracerebral corticosterone actions on the facilitation of long-lasting subordinate behavior, likely by having a modulatory role in the neurobehavioral plasticity engaged in the shaping of social subordination.

Competition, testosterone, and adult neurobehavioral plasticity.

Motivation in performance is often measured via competitions. Winning a competition has been found to increase the motivation to perform in subsequent competitions. One potential neurobiological mechanism that regulates the motivation to compete involves sex hormones, such as the steroids testosterone and estradiol. A wealth of studies in both nonhuman animals and humans have shown that a rise in testosterone levels before and after winning a competition enhances the motivation to compete. There is strong evidence for acute behavioral effects in response to steroid hormones. Intriguingly, a substantial testosterone surge following a win also appears to improve an individual's performance in later contests resulting in a higher probability of winning again. These effects may occur via androgen and estrogen pathways modulating dopaminergic regions, thereby behavior on longer timescales. Hormones thus not only regulate and control social behavior but are also key to adult neurobehavioral plasticity. Here, we present literature showing hormone-driven behavioral effects that persist for extended periods of time beyond acute effects of the hormone, highlighting a fundamental role of sex steroid hormones in adult neuroplasticity. We provide an overview of the relationship between testosterone, motivation measured from objective effort, and their influence in enhancing subsequent effort in competitions. Implications for an important role of testosterone in enabling neuroplasticity to improve performance will be discussed.

Enhanced cocaine-induced locomotor sensitization and intrinsic excitability of NAc medium spiny neurons in adult but not in adolescent rats susceptible to diet-induced obesity.

Basal and diet-induced differences in mesolimbic function, particularly within the nucleus accumbens (NAc), may contribute to human obesity; these differences may be more pronounced in susceptible populations. We examined differences in cocaine-induced behavioral plasticity in rats that are susceptible vs. resistant to diet-induced obesity and basal differences in striatal neuron function in adult and in adolescent obesity-prone and obesity-resistant rats. Susceptible and resistant outbred rats were identified based on "junk-food" diet-induced obesity. Then, the induction and expression of cocaine-induced locomotor sensitization, which is mediated by enhanced striatal function and is associated with increased motivation for rewards and reward-paired cues, were evaluated. Basal differences in mesolimbic function were examined in selectively bred obesity-prone and obesity-resistant rats (P70-80 and P30-40) using both cocaine-induced locomotion and whole-cell patch clamping approaches in NAc core medium spiny neurons (MSNs). In rats that became obese after eating junk-food, the expression of locomotor sensitization was enhanced compared to non-obese rats, with similarly strong responses to 7.5 and 15mg/kg cocaine. Without diet manipulation, obesity-prone rats were hyper-responsive to the acute locomotor-activating effects of cocaine, and the intrinsic excitability of NAc core MSNs was enhanced by ∼60% at positive and negative potentials. These differences were present in adult, but not adolescent rats. Post-synaptic glutamatergic transmission was similar between groups. Mesolimbic systems, particularly NAc MSNs, are hyper-responsive in obesity-prone individuals, and interactions between predisposition and experience influence neurobehavioral plasticity in ways that may promote weight gain and hamper weight loss in susceptible rats.

Blunted behavioral and molecular responses to chronic mild stress in adult rats with experience of infancy maternal separation.

Childhood adversity has profound and persistent effects on brain functions and has been implicated in the etiology of depression. Brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB) play critical roles during brain development to maintain neuronal function and structural integrity in adulthood. We therefore investigated the long-term effects of early life adversity on the depression-related behavior and the expression of BDNF and CREB in the hippocampus. Male Sprague-Dawley newborn rats were subjected to maternal separation for 3 h/day on postnatal days 2-14. After the postnatal day 90, rats with or without the experience of infancy maternal separation received a series of unpredictable chronic mild stress (CMS) for 21 days. Sucrose preference and spontaneous activity in the open field test were recorded, and the expression of BDNF and CREB in the hippocampus was measured by real-time RT-PCR and Western blot analyses. Before exposure to CMS, the rats with maternal separation showed the significant decreases in sucrose preference, spontaneous activity, and hippocampal expression of BDNF and CREB, compared to the animals without maternal separation. In contrast, the rats without maternal separation showed greater decreases of the above indictors after CMS, the levels of which were lower than those observed in the rats with maternal separation. Thus, early life adversity leads to long-term decreases in the capacity of enjoying sweetness, spontaneous activity, and hippocampal expression of BDNF and CREB. Moreover, childhood neglect may decrease the neurobehavioral plasticity, thereby blunting the responses to adulthood stress and increasing the susceptibility to depression.

The trace amine associated receptor 1 agonist RO5263397 attenuates the induction of cocaine behavioral sensitization in rats

The trace amine associated receptor (TAAR) 1 is a new G protein coupled receptor that critically modulates central dopaminergic system. Recently, several selective TAAR 1 ligands have been described to possess antipsychotic and antidepressant-like activities. However, it is unknown of the role of these ligands in modulating psychostimulant-induced neurobehavioral plasticity. This study examined the effects of a selective TAAR 1 agonist, RO5263397, on cocaine induced behavioral sensitization in rats, a rodent model of drug-induced behavioral plasticity. Daily treatment with 15mg/kg cocaine (i.p., 7 days) induced robust locomotor sensitization in rats. RO5263397 (1–10mg/kg, i.p.) alone did not significantly alter the locomotor activity. Acute treatment with RO5263397 (3.2 and 10mg/kg) did not significantly modify cocaine-induced hyperactivity; however, the induction of locomotor sensitization was significantly blocked after 7 days of daily RO5263397 treatment. More importantly, the expression of locomotor sensitization remained significantly attenuated when rats were re-tested 7 days after the last drug treatment. The marked attenuation of cocaine sensitization was also evidenced by the suppression of the dose-effect function (3.2–32mg/kg) of cocaine sensitization. Together, these data represent the first to report a critical modulatory role of TAAR 1 agonists in cocaine-induced behavioral plasticity, which may be indicative of its potential role for altering other long-lasting behavioral maladaptations of cocaine including drug addiction.

Ketamine Decreases Resting State Functional Network Connectivity in Healthy Subjects: Implications for Antidepressant Drug Action

Increasing preclinical and clinical evidence underscores the strong and rapid antidepressant properties of the glutamate-modulating NMDA receptor antagonist ketamine. Targeting the glutamatergic system might thus provide a novel molecular strategy for antidepressant treatment. Since glutamate is the most abundant and major excitatory neurotransmitter in the brain, pathophysiological changes in glutamatergic signaling are likely to affect neurobehavioral plasticity, information processing and large-scale changes in functional brain connectivity underlying certain symptoms of major depressive disorder. Using resting state functional magnetic resonance imaging (rsfMRI), the „dorsal nexus “(DN) was recently identified as a bilateral dorsal medial prefrontal cortex region showing dramatically increased depression-associated functional connectivity with large portions of a cognitive control network (CCN), the default mode network (DMN), and a rostral affective network (AN). Hence, Sheline and colleagues (2010) proposed that reducing increased connectivity of the DN might play a critical role in reducing depression symptomatology and thus represent a potential therapy target for affective disorders. Here, using a randomized, placebo-controlled, double-blind, crossover rsfMRI challenge in healthy subjects we demonstrate that ketamine decreases functional connectivity of the DMN to the DN and to the pregenual anterior cingulate (PACC) and medioprefrontal cortex (MPFC) via its representative hub, the posterior cingulate cortex (PCC). These findings in healthy subjects may serve as a model to elucidate potential biomechanisms that are addressed by successful treatment of major depression. This notion is further supported by the temporal overlap of our observation of subacute functional network modulation after 24 hours with the peak of efficacy following an intravenous ketamine administration in treatment-resistant depression.

Rapid neural circuit switching mediated by synaptic plasticity during neural morphallactic regeneration

The aquatic oligochaete, Lumbriculus variegatus (Lumbriculidae), undergoes a rapid regenerative transformation of its neural circuits following body fragmentation. This type of nervous system plasticity, called neural morphallaxis, involves the remodeling of the giant fiber pathways that mediate rapid head and tail withdrawal behaviors. Extra- and intracellular electrophysiological recordings demonstrated that changes in cellular properties and synaptic connections underlie neurobehavioral plasticity during morphallaxis. Sensory-to-giant interneuron connections, undetectable prior to body injury, emerged within hours of segment amputation. The appearance of functional synaptic transmission was followed by interneuron activation, coupling of giant fiber spiking to motor outputs and overt segmental shortening. The onset of morphallactic plasticity varied along the body axis and emerged more rapidly in segments closer to regions of sensory field overlap between the two giant fiber pathways. The medial and lateral giant fibers were simultaneously activated during a transient phase of network remodeling. Thus, synaptic plasticity at sensory-to-giant interneuron connections mediates escape circuit morphallaxis in this regenerating annelid worm.

The neuroethics of non-invasive brain stimulation

Transcranial direct current stimulation (TDCS) is a brain stimulation tool that is portable, painless, inexpensive, apparently safe, and with potential long-term efficacy. Recent results obtained from TDCS experiments offer exciting possibilities for the enhancement and treatment of normal or impaired abilities, respectively. We discuss new neuroethical problems that have emerged from the usage of TDCS, and also focus on one of the most likely future applications of TDCS: enhancing learning and cognition in children with typical and atypical development.