Mechanisms Of Neural Plasticity Research Articles

Synchronous Measurements of Extracellular Action Potentials and Neurochemical Activity with Carbon Fiber Electrodes in Nonhuman Primates.

Measuring the dynamic relationship between neuromodulators, such as dopamine, and neuronal action potentials is imperative to understand how these fundamental modes of neural signaling interact to mediate behavior. We developed methods to measure concurrently dopamine and extracellular action potentials (i.e., spikes) in monkeys. Standard fast-scan cyclic voltammetric (FSCV) electrochemical (EChem) and electrophysiological (EPhys) recording systems are combined and used to collect spike and dopamine signals, respectively, from an array of carbon fiber (CF) sensors implanted in the monkey striatum. FSCV requires the application of small voltages at the implanted sensors to measure redox currents generated from target molecules, such as dopamine. These applied voltages create artifacts at neighboring EPhys measurement sensors which may lead to misclassification of these signals as physiological spikes. Therefore, simple automated temporal interpolation algorithms were designed to remove these artifacts and enable accurate spike extraction. We validated these methods using simulated artifacts and demonstrated an average spike recovery rate of 84.5%. We identified and discriminated cell type-specific units in the monkey striatum that were shown to correlate to specific behavioral task parameters related to reward size and eye movement direction. Synchronously recorded spike and dopamine signals displayed contrasting relations to the task variables, suggesting a complex relationship between these two modes of neural signaling. Future application of our methods will help advance our understanding of the interactions between neuromodulator signaling and neuronal activity, to elucidate more detailed mechanisms of neural circuitry and plasticity mediating behaviors in health and in disease.

Myelin plasticity in the ventral tegmental area is required for opioid reward

All drugs of abuse induce long-lasting changes in synaptic transmission and neural circuit function that underlie substance-use disorders1,2. Another recently appreciated mechanism of neural circuit plasticity is mediated through activity-regulated changes in myelin that can tune circuit function and influence cognitive behaviour3–7. Here we explore the role of myelin plasticity in dopaminergic circuitry and reward learning. We demonstrate that dopaminergic neuronal activity-regulated myelin plasticity is a key modulator of dopaminergic circuit function and opioid reward. Oligodendroglial lineage cells respond to dopaminergic neuronal activity evoked by optogenetic stimulation of dopaminergic neurons, optogenetic inhibition of GABAergic neurons, or administration of morphine. These oligodendroglial changes are evident selectively within the ventral tegmental area but not along the axonal projections in the medial forebrain bundle nor within the target nucleus accumbens. Genetic blockade of oligodendrogenesis dampens dopamine release dynamics in nucleus accumbens and impairs behavioural conditioning to morphine. Taken together, these findings underscore a critical role for oligodendrogenesis in reward learning and identify dopaminergic neuronal activity-regulated myelin plasticity as an important circuit modification that is required for opioid reward.

Advancing Neuro-Inspired Lifelong Learning for Edge with Co-Design

Lifelong learning, which refers to an agent's ability to continuously learn and enhance its performance over its lifespan, is a significant challenge in artificial intelligence (AI), that biological systems tackle efficiently. This challenge is further exacerbated when AI is deployed in untethered environments with strict energy and latency constraints. We take inspiration from neural plasticity and investigate how to leverage and build energy-efficient lifelong learning machines. Specifically, we study how a combination of neural plasticity mechanisms, namely neuromodulation, synaptic consolidation, and metaplasticity, enhance the continual learning capabilities of AI models. We further co-design architectures that leverage compute-in-memory topologies and sparse spike-based communication with quantization for the edge. Aspects of this co-design can be transferred to federated lifelong learning scenarios.

The Effectiveness of Paired Associative Stimulation on Motor Recovery after Stroke: A Scoping Review.

Paired associative stimulation (PAS) is a non-invasive brain stimulation technique combining transcranial magnetic stimulation and peripheral nerve stimulation. PAS allows connections between cortical areas and peripheral nerves (C/P PAS) or between cortical regions (C/C PAS) to be strengthened or weakened by spike-timing-dependent neural plasticity mechanisms. Since PAS modulates both neurophysiological features and motor performance, there is growing interest in its application in neurorehabilitation. We aimed to synthesize evidence on the motor rehabilitation role of PAS in stroke patients. We performed a literature search following the PRISMA Extension for Scoping Reviews Framework. Eight studies were included: one investigated C/C PAS between the cerebellum and the affected primary motor area (M1), seven applied C/P PAS over the lesional, contralesional, or both M1. Seven studies evaluated the outcome on upper limb and one on lower limb motor recovery. Although several studies omit crucial methodological details, PAS highlighted effects mainly on corticospinal excitability, and, more rarely, an improvement in motor performance. However, most studies failed to prove a correlation between neurophysiological changes and motor improvement. Although current studies seem to suggest a role of PAS in post-stroke rehabilitation, their heterogeneity and limited number do not yet allow definitive conclusions to be drawn.

Gaming expertise induces meso‑scale brain plasticity and efficiency mechanisms as revealed by whole-brain modeling

Video games are a valuable tool for studying the effects of training and neural plasticity on the brain. However, the underlying mechanisms related to plasticity-associated brain structural changes and their impact on brain dynamics are unknown. Here, we used a semi-empirical whole-brain model to study structural neural plasticity mechanisms linked to video game expertise. We hypothesized that video game expertise is associated with neural plasticity-mediated changes in structural connectivity that manifest at the meso‑scale level, resulting in a more segregated functional network topology. To test this hypothesis, we combined structural connectivity data of StarCraft II video game players (VGPs, n = 31) and non-players (NVGPs, n = 31), with generic fMRI data from the Human Connectome Project and computational models, to generate simulated fMRI recordings. Graph theory analysis on simulated data was performed during both resting-state conditions and external stimulation. VGPs’ simulated functional connectivity was characterized by a meso‑scale integration, with increased local connectivity in frontal, parietal, and occipital brain regions. The same analyses at the level of structural connectivity showed no differences between VGPs and NVGPs. Regions that increased their connectivity strength in VGPs are known to be involved in cognitive processes crucial for task performance such as attention, reasoning, and inference. In-silico stimulation suggested that differences in FC between VGPs and NVGPs emerge in noisy contexts, specifically when the noisy level of stimulation is increased. This indicates that the connectomes of VGPs may facilitate the filtering of noise from stimuli. These structural alterations drive the meso‑scale functional changes observed in individuals with gaming expertise. Overall, our work sheds light on the mechanisms underlying structural neural plasticity triggered by video game experiences.

Brain Derived Neurotrophic Factor (BDNF) Immunolabeling in C4-C5 Spinal Cord of Adult Female Rats Following Acute Intermittent Hypoxia (AIH) Exposure Composed of 5,3-min Hypoxic Episodes (AIH5x3min) at 4-weeks After mid-thoracic SCI

Acute intermittent hypoxia (AIH) induces spinal neural plasticity in both respiratory and non-respiratory somatic motor systems. AIH-induced neural plasticity has been best studied in the respiratory neural control system, where exposure to moderate AIH (9-15% inspired O2), typically composed of 3,5-min hypoxic episodes (AIH3x5min), has been shown to consistently elicit a robust increase in phrenic motor activity due to a serotonin-dependent mechanism that promotes de novo synthesis of BDNF and activation of high affnity BDNF-TrkB receptors to initiate ERK MAP kinase signaling in phrenic motoneurons. Whether other protocols that use a total duration of 15 min of hypoxic exposure, but with an increased number of shorter duration hypoxic episodes ( e.g, AIH5x3min) similarly elicit serotonin-dependent BDNF pathway-mediated neural plasticity mechanisms in this region remains to be determined. To begin to assess this possibility, we evaluated BDNF expression in C4-C5 spinal cord segments containing the phrenic motor nucleus following single exposure to AIH5x3min (12% O2) in urethane-anesthetized spontaneously breathing adult female rats at 4-weeks after mid-thoracic SCI. Experiments using AIH3x5min (12% O2) exposure and intermittent normoxia (Nx, 21% O2) exposure served as controls. At ~60-90 min after the AIH or Nx exposure protocol, the rats were transcardially perfused with saline followed by 4% PFA, and various regions of the CNS, including the C3-C5 spinal cord were removed, post-fixed, and cryoprotected. 20 μm thick transverse sections were then cut to obtain sets of slides for single- or double-label fluorescence IHC staining to localize BDNF protein expression in the C4-C5 spinal cord, including the region containing the phrenic motor nucleus. Preliminary analyses show that both AIH5x3min and AIH3x5min exposures elicit increased BDNF expression when compared to Nx exposure, with both diffuse cytosolic and punctate immunofluorescence labeling in and around neurons within the phrenic motor nucleus region, including labeling of presumptive phrenic motoneurons. No labeling was seen in adjacent tissue sections that were incubated without the primary antibody. Immunofluorescence labeling was also seen in the more medial regions of lamina VIII in the ventral horn, the medial regions of laminae VI and VII, and throughout lamina X; these regions have been reported to contain the V0-V3 classes of spinal interneurons (SpINs) albeit we did not verify BDNF labeling of specific classes of presumptive SpINs. These preliminary observations suggest that AIH5x3min exposure likely recruits a serotonin-dependent BDNF pathway-mediated mechanism for neural plasticity in a manner similar to that seen for AIH3x5min exposure. APS Summer Undergraduate Research Fellowship; DOD CDMRP W81XWH-17-1-0260; NYS DOH SCIRB C37711GG. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Центральные слуховые расстройства: причины, симптомы и способы преодоления дефицита в условиях учебного процесса

<p style="text-align: justify;">Central Auditory Processing Disorders (CAPD) are impairments in the ability to recognize sounds, localize their sources, and/or determine their identity and meaning due to functional impairments of the central auditory system. CAPD is observed in individuals with normal hearing levels and is not the result of high-level speech or cognitive impairment. This disorder is not well known to Russian specialists in the field of correctional psychology, while according to foreign sources it is observed in 2—7% of schoolchildren and is often combined with other developmental disorders (dyslexia, speech developmental disorders, ASD, ADHD). Here we provide a brief review of CAPD: its causes, symptoms, and approaches to diagnosis. In particular, we draw the readers' attention to the insufficient development of tools and practices for diagnosing and treating CAPD in Russia. Next, we review current approaches to the correction of CAPD, with special emphasis on assistive technologies that improve the signal-to-noise ratio (FM systems). Evidence in the literature indicates that in addition to the immediate effect (improved speech understanding), prolonged use of FM systems has a positive long-term effect based on mechanisms of neural plasticity.</p>

Neuroadaptive Tracking Control of Affine Nonlinear Systems Using Echo State Networks Embedded With Multiclustered Structure and Intrinsic Plasticity.

In this article, we present an echo state network (ESN)-based tracking control approach for a class of affine nonlinear systems. Different from the most existing neural-network (NN)-based control methods that are focused on the feedforward NN, the proposed method adopts a bioinspired recurrent NN fusing with multiple cluster and intrinsic plasticity (IP) to deal with modeling uncertainties and coupling nonlinearities in the systems. The key features of this work can be summarized as follows: 1) the proposed control is built upon the ESN embedded with multiclustered reservoir inspired from the hierarchically clustered organizations of cortical connections in mammalian brains; 2) the developed neuroadaptive control scheme utilizes unsupervised learning rules inspired from the neural plasticity mechanism of the individual neuron in nervous systems, called IP; 3) a multiclustered reservoir with IP is integrated into the algorithm to enhance the approximation performance of NN; and 4) the multiclustered reservoir is constructed offline and is task-independent, rendering the proposed method less expensive in computation. The effectiveness of the method is also confirmed by comparison with the existing neuroadaptive methods via numerical simulations, demonstrating that better tracking precision is achieved by the proposed method.

Neural mechanisms of associative cortical plasticity in cognitive domain: Magnetoencephalographic studies

Acquisition of language semantics is widely believed to be facilitated by biological mechanisms of associative learning [1]. However, current understanding of brain mechanisms underlying learning and memory is primarily based on simple models, including animal models, with mechanisms of learning in the cognitive realm largely unknown. Semantic language learning serves as a compelling example of these cognitive processes, whose brain mechanisms pose a challenge to explanation at the level of basic neural networks. Particularly, many processes underlying such learning still lack clear understanding, including the mechanisms that enable correlational coincidence of neuronal representation required for Hebbian plasticity, the reverberatory replay of the to-be associated representations in working memory, and the involvement of consolidation, among others. We conducted a series of studies modeling the acquisition of semantic knowledge of action-related vocabulary to investigate these questions. We implemented a unique trial-and-error-based procedure for semantic acquisition, in which participants obtained associations between newly introduced pseudowords and actions through active learning. The experimental procedure comprised the delivery of acoustically equivalent pseudowords that were previously unknown to the subjects. Participants were instructed to execute movements of their hands and feet in response to specific pseudowords. Following each trial, participants received either positive or negative feedback depending on their performance. During the learning phase, MEG was recorded, as well as during passive presentations of the same pseudowords before and after learning to control for attention and motor preparation effects. Our analysis involved event-related fields and beta oscillations. Our experiments showed that cortical plasticity related to word learning could be detected immediately after learning, without the need for prolonged consolidation time [2]. We observed two effects during learning that could contribute to Hebbian plasticity by linking auditory speech representations of pseudowords with associated movements. First, we observed the reactivation of auditory speech representations during the initialization of movement. This mechanism apparently creates the conditions for temporal coincidence of activations in two representations, specifically an auditory speech representation and a representation of a motor program. During the learning process, we observed a considerable rise in beta oscillations that occurred during and after action execution. This effect comprised a typical beta-rebound in the sensorimotor regions and a significant surge in beta activity in various associative cortical regions. We postulate that these beta oscillations constitute a reverberation mechanism that reinforces the associative connection and guards it against potential interference [3]. In further experiments, we administered the learning process over two consecutive days with an overnight interval between recordings. We evaluated beta power dynamics during the acquisition of novel pseudowords on day 1 and during task rehearsal following overnight sleep on day 2. Beta event-related synchronization in the frontal regions emerged upon the attainment of the pseudoword learning rules on day 1, and remained unchanged after sleep and subsequent rehearsal on day 2. The prefrontal beta rhythm’s dynamics mirrored the corresponding behavioral changes: subjects executed the task with minimal errors on day 2 upon meeting the learning criterion on day 1. Beta event-related synchronization augmented continuously in the posterior temporal and parietal cortices on day 2 and potentially contributed towards the assimilation of newly-acquired associations in long-term memory. In summary, our research offers fresh perspectives on the intricate neural mechanisms underlying plasticity in the human brain within the cognitive domain.

Considering intersectionality and interacting levels of early intervention on early brain development-a commentary on Nelson etal. (2023).

It has long been recognized that an individual's experiences can metaphorically 'get under the skin' and become biologically embedded, thus affecting behavior and life outcomes (Hertzman, 2012). While this term is most often used to describe how adverse experiences influence biological process, it is rarely discussed how the same can be said of positive experiences, such as intervention to prevent or treat negative outcomes. In their annual review, Nelson etal. (2023) provide a timely and comprehensive review of how early intervention capitalizes on the neuroplasticity of the postnatal years, turning periods of 'vulnerability' to ones of 'opportunity'. Drawing on decades of expertise, they discuss the neurobiological mechanisms of intervention in two contexts: caregiving interventions for children growing up in disadvantaged environments, and therapeutic interventions for children at elevated risk of neurodevelopmental disorders such as Autism. They thought-provokingly describe both how early intervention operates through mechanisms of neural plasticity and how this can and should inform policy decisions to provide the greatest benefit to children. Here, I aim to underscore the importance of this review by addressing the intersection of these topics; specifically, I muse on how the scientific discovery of biological processes and the ethical imperative to support vulnerable children's development are intimately intertwined, and how this highlights both critical lines of future inquiry as well as policy implications.

Selectivity to acoustic features of human speech in the auditory cortex of the mouse

A better understanding of the neural mechanisms of speech processing can have a major impact in the development of strategies for language learning and in addressing disorders that affect speech comprehension. Technical limitations in research with human subjects hinder a comprehensive exploration of these processes, making animal models essential for advancing the characterization of how neural circuits make speech perception possible. Here, we investigated the mouse as a model organism for studying speech processing and explored whether distinct regions of the mouse auditory cortex are sensitive to specific acoustic features of speech. We found that mice can learn to categorize frequency-shifted human speech sounds based on differences in formant transitions (FT) and voice onset time (VOT). Moreover, neurons across various auditory cortical regions were selective to these speech features, with a higher proportion of speech-selective neurons in the dorso-posterior region. Last, many of these neurons displayed mixed-selectivity for both features, an attribute that was most common in dorsal regions of the auditory cortex. Our results demonstrate that the mouse serves as a valuable model for studying the detailed mechanisms of speech feature encoding and neural plasticity during speech-sound learning.

Exploring the association between circRNA expression and pediatric obesity based on a case–control study and related bioinformatics analysis

ObjectiveOur present study utilized case–control research to explore the relationship between specific circRNAs and pediatric obesity through a literature review and bioinformatics and to predict their possible biological functions, providing ideas for epigenetic mechanism studies of pediatric obesity.MethodsCircRNAs related to pediatric obesity were preliminarily screened by a literature review and qRT–PCR. CircRNA expression in children with obesity (n = 75) and control individuals (n = 75) was confirmed with qRT–PCR in a case–control study. This was followed by bioinformatics analyses, such as GO analysis, KEGG pathway analysis, and ceRNA network construction. Multivariate logistic regression was utilized to analyze the effects of circRNAs on obesity. A receiver operating characteristic (ROC) curve was also drawn to explore the clinical application value of circRNAs in pediatric obesity.ResultsHas_circ_0046367 and hsa_circ_0000284 were separately validated to be statistically downregulated and upregulated, respectively, in the peripheral blood mononuclear cells of children with obesity and revealed as independent indicators of increased CHD risk [hsa_circ_0046367 (OR = 0.681, 95% CI: 0.480 ~ 0.967) and hsa_circ_0000284 (OR = 1.218, 95% CI: 1.041 ~ 1.424)]. The area under the ROC curve in the combined analysis of hsa_circ_0046367 and hsa_circ_0000284 was 0.706 (95% CI: 0.623 ~ 0.789). Enrichment analyses revealed that these circRNAs were actively involved in neural plasticity mechanisms, cell secretion and signal regulation.ConclusionThe present research revealed that low expression of hsa_circ_0046367 and high expression of hsa_circ_0000284 are risk factors for pediatric obesity and that neural plasticity mechanisms are closely related to obesity.

Increased proliferation and neuronal fate in prairie vole brain progenitor cells cultured in vitro: effects by social exposure and sexual dimorphism

BackgroundThe prairie vole (Microtus ochrogaster) is a socially monogamous rodent that establishes an enduring pair bond after cohabitation, with (6 h) or without (24 h) mating. Previously, we reported that social interaction and mating increased cell proliferation and differentiation to neuronal fate in neurogenic niches in male voles. We hypothesized that neurogenesis may be a neural plasticity mechanism involved in mating-induced pair bond formation. Here, we evaluated the differentiation potential of neural progenitor cells (NPCs) isolated from the subventricular zone (SVZ) of both female and male adult voles as a function of sociosexual experience. Animals were assigned to one of the following groups: (1) control (Co), sexually naive female and male voles that had no contact with another vole of the opposite sex; (2) social exposure (SE), males and females exposed to olfactory, auditory, and visual stimuli from a vole of the opposite sex, but without physical contact; and (3) social cohabitation with mating (SCM), male and female voles copulating to induce pair bonding formation. Subsequently, the NPCs were isolated from the SVZ, maintained, and supplemented with growth factors to form neurospheres in vitro.ResultsNotably, we detected in SE and SCM voles, a higher proliferation of neurosphere-derived Nestin + cells, as well as an increase in mature neurons (MAP2 +) and a decrease in glial (GFAP +) differentiated cells with some sex differences. These data suggest that when voles are exposed to sociosexual experiences that induce pair bonding, undifferentiated cells of the SVZ acquire a commitment to a neuronal lineage, and the determined potential of the neurosphere is conserved despite adaptations under in vitro conditions. Finally, we repeated the culture to obtain neurospheres under treatments with different hormones and factors (brain-derived neurotrophic factor, estradiol, prolactin, oxytocin, and progesterone); the ability of SVZ-isolated cells to generate neurospheres and differentiate in vitro into neurons or glial lineages in response to hormones or factors is also dependent on sex and sociosexual context.ConclusionSocial interactions that promote pair bonding in voles change the properties of cells isolated from the SVZ. Thus, SE or SCM induces a bias in the differentiation potential in both sexes, while SE is sufficient to promote proliferation in SVZ-isolated cells from male brains. In females, proliferation increases when mating is performed. The next question is whether the rise in proliferation and neurogenesis of cells from the SVZ are plastic processes essential for establishing, enhancing, maintaining, or accelerating pair bond formation.HighlightsSociosexual experiences that promote pair bonding (social exposure and social cohabitation with mating) induce changes in the properties of neural stem/progenitor cells isolated from the SVZ in adult prairie voles.Social interactions lead to increased proliferation and induce a bias in the differentiation potential of SVZ-isolated cells in both male and female voles.The differentiation potential of SVZ-isolated cells is conserved under in vitro conditions, suggesting a commitment to a neuronal lineage under a sociosexual context.Hormonal and growth factors treatments (brain-derived neurotrophic factor, estradiol, prolactin, oxytocin, and progesterone) affect the generation and differentiation of neurospheres, with dependencies on sex and sociosexual context.Proliferation and neurogenesis in the SVZ may play a crucial role in establishing, enhancing, maintaining, or accelerating pair bond formation.

Effects of repetitive transcranial magnetic stimulation on episodic memory in patients with subjective cognitive decline: study protocol for a randomized clinical trial.

Early decline of episodic memory is detectable in subjective cognitive decline (SCD). The left dorsolateral prefrontal cortex (DLPFC) is associated with encoding episodic memories. Repetitive transcranial magnetic stimulation (rTMS) is a novel and viable tool to improve cognitive function in Alzheimer's disease (AD) and mild cognitive impairment, but the treatment effect in SCD has not been studied. We aim to investigate the efficacy of rTMS on episodic memory in individuals with SCD, and to explore the potential mechanisms of neural plasticity. In our randomized, sham-controlled trial, patients (n = 60) with SCD will receive 20 sessions (5 consecutive days per week for 4 weeks) of real rTMS (n = 30) or sham rTMS (n = 30) over the left DLPFC. The primary outcome is the Auditory Verbal Learning Test-Huashan version (AVLT-H). Other neuropsychological examinations and the long-term potentiation (LTP)-like cortical plasticity evaluation serve as the secondary outcomes. These outcomes will be assessed before and at the end of the intervention. If the episodic memory of SCD improve after the intervention, the study will confirm that rTMS is a promising intervention for cognitive function improvement on the early stage of dementia. This study will also provide important clinical evidence for early intervention in AD and emphasizes the significance that impaired LTP-like cortical plasticity may be a potential biomarker of AD prognosis by demonstrating the predictive role of LTP on cognitive improvement in SCD. The study was approved by the Human Research Ethics Committee of the hospital (No. 2023-002-01). The results will be published in peer-review publications. https://www.chictr.org.cn/, identifier ChiCTR2300075517.

Targeting Neurogenesis in Seeking Novel Treatments for Ischemic Stroke.

The interruption of cerebral blood flow leads to ischemic cell death and results in ischemic stroke. Although ischemic stroke is one of the most important causes of long-term disability and mortality, limited treatments are available for functional recovery. Therefore, extensive research has been conducted to identify novel treatments. Neurogenesis is regarded as a fundamental mechanism of neural plasticity. Therefore, therapeutic strategies targeting neurogenesis are thought to be promising. Basic research has found that therapeutic intervention including cell therapy, rehabilitation, and pharmacotherapy increased neurogenesis and was accompanied by functional recovery after ischemic stroke. In this review, we consolidated the current knowledge of the relationship between neurogenesis and treatment for ischemic stroke. It revealed that many treatments for ischemic stroke, including clinical and preclinical ones, have enhanced brain repair and functional recovery post-stroke along with neurogenesis. However, the intricate mechanisms of neurogenesis and its impact on stroke recovery remain areas of extensive research, with numerous factors and pathways involved. Understanding neurogenesis will lead to more effective stroke treatments, benefiting not only stroke patients but also those with other neurological disorders. Further research is essential to bridge the gap between preclinical discoveries and clinical implementation.

Learning induces EPO/EPOr expression in memory relevant brain areas, whereas exogenously applied EPO promotes remote memory consolidation.

Memory and learning allow animals to appropriate certain properties of nature with which they can navigate in it successfully. Memory is acquired slowly and consists of two major phases, a fragile early phase (short-term memory, <4h) and a more robust and long-lasting late one (long-term memory, >4h). Erythropoietin (EPO) prolongs memory from 24 to 72h when animals are trained for 5min in a place recognition task but not when training lasted 3min (short-term memory). It is not known whether it promotes the formation of remote memory (≥21 days). We address whether the systemic administration of EPO can convert a short-term memory into a long-term remote memory, and the neural plasticity mechanisms involved. We evaluated the effect of training duration (3 or 5min) on the expression of endogenous EPO and its receptor to shed light on the role of EPO in coordinating mechanisms of neural plasticity using a single-trial spatial learning test. We administered EPO 10min post-training and evaluated memory after 24h, 96h, 15 days, or 21 days. We also determined the effect of EPO administered 10min after training on the expression of arc and bdnf during retrieval at 24h and 21 days. Data show that learning induces EPO/EPOr expression increase linked to memory extent, exogenous EPO prolongs memory up to 21 days; and prefrontal cortex bdnf expression at 24h and in the hippocampus at 21 days, whereas arc expression increases at 21 days in the hippocampus and prefrontal cortex.

Rapid, Activity-Dependent Intrinsic Plasticity in the Developing Zebra Finch Auditory Cortex.

The acoustic environment an animal experiences early in life shapes the structure and function of its auditory system. This process of experience-dependent development is thought to be primarily orchestrated by potentiation and depression of synapses, but plasticity of intrinsic voltage dynamics may also contribute. Here, we show that in juvenile male and female zebra finches, neurons in a cortical-level auditory area, the caudal mesopallium (CM), can rapidly change their firing dynamics. This plasticity was only observed in birds that were reared in a complex acoustic and social environment, which also caused increased expression of the low-threshold potassium channel Kv1.1 in the plasma membrane and endoplasmic reticulum (ER). Intrinsic plasticity depended on activity, was reversed by blocking low-threshold potassium currents, and was prevented by blocking intracellular calcium signaling. Taken together, these results suggest that Kv1.1 is rapidly mobilized to the plasma membrane by activity-dependent elevation of intracellular calcium. This produces a shift in the excitability and temporal integration of CM neurons that may be permissive for auditory learning in complex acoustic environments during a crucial period for the development of vocal perception and production.SIGNIFICANCE STATEMENT Neurons can change not only the strength of their connections to other neurons, but also how they integrate synaptic currents to produce patterns of action potentials. In contrast to synaptic plasticity, the mechanisms and functional roles of intrinisic plasticity remain poorly understood. We found that neurons in the zebra finch auditory cortex can rapidly shift their spiking dynamics within a few minutes in response to intracellular stimulation. This plasticity involves increased conductance of a low-threshold potassium current associated with the Kv1.1 channel, but it only occurs in birds reared in a rich acoustic environment. Thus, auditory experience regulates a mechanism of neural plasticity that allows neurons to rapidly adapt their firing dynamics to stimulation.

An fMRI study of how deaf children process the two tones (first tone and third tone) in Mandarin Chinese

The objective of this study is to investigate the brain activity patterns of deaf children and hearing children during the processing of two different tones (first tone and third tone) using resting-state functional magnetic resonance imaging (fMRI). Furthermore, the study aims to identify the differences in brain activation regions between deaf children and hearing children during the tone processing task. Five deaf children and two hearing children were selected as participants. Resting-state functional magnetic resonance imaging (fMRI) scans were conducted on the subjects using an fMRI scanner. The acquired fMRI data were then preprocessed and analyzed to examine the patterns of brain activity. Deaf children and hearing children exhibit differences in brain activation regions during the execution of tone recognition tasks. These differences can be observed in various areas such as the pre-central gyrus, superior temporal gyrus, middle occipital gyrus, supplementary motor area and interior frontal gyrus, among others. The results suggest that deaf children may rely on different neural networks to process tone information compared to hearing children, possibly exhibiting stronger neural plasticity and compensatory mechanisms. These findings contribute to the understanding of the neural basis of tone processing and may help in refining intervention strategies.

Acupuncture Alleviates CUMS-Induced Depression-Like Behaviors by Restoring Prefrontal Cortex Neuroplasticity.

To explore the therapeutic efficiency of acupuncture and the related molecular mechanism of neural plasticity in depression. Chronic unpredictable mild stress- (CUMS-) induced rats were established for the depression animal model. There were a total of four rat groups, including the control group, the CUMS group, the CUMS+acupuncture group, and the CUMS+fluoxetine group. The acupuncture group and the fluoxetine group were given a 3-week treatment after the modeling intervention. The researcher performed the open-field, elevated plus maze, and sucrose preference tests to evaluate depressive behaviors. The number of nerve cells, dendrites' length, and the prefrontal cortex's spine density were detected using Golgi staining. The prefrontal cortex expression, such as BDNF, PSD95, SYN, and PKMZ protein, was detected using the western blot and RT-PCR. Acupuncture could alleviate depressive-like behaviors and promote the recovery of the neural plasticity functions in the prefrontal cortex, showing the increasing cell numbers, prolonging the length of the dendrites, and enhancing the spine density. The neural plasticity-related proteins in the prefrontal cortex, including BDNF, PSD95, SYN, and PKMZ, were all downregulated in the CUMS-induced group; however, these effects could be partly reversed after being treated by acupuncture and fluoxetine (P < 0.05). Acupuncture can ameliorate depressive-like behaviors by promoting the recovery of neural plasticity functions and neural plasticity-related protein upregulation in the prefrontal cortex of CUMS-induced depressed rats. Our study provides new insights into the antidepressant approach, and further studies are warranted to elucidate the mechanisms of acupuncture involved in depression treatment.

Self-Regulatory Neuronal Mechanisms and Long-Term Challenges in Schizophrenia Treatment.

Schizophrenia is a chronic and relapsing disorder that is characterized not only by delusions and hallucinations but also mainly by the progressive development of cognitive and social deficits. These deficits are related to impaired synaptic plasticity and impaired neurotransmission in the nervous system. Currently, technological innovations and medical advances make it possible to use various self-regulatory methods to improve impaired synaptic plasticity. To evaluate the therapeutic effect of various rehabilitation methods, we reviewed methods that modify synaptic plasticity and improve the cognitive and executive processes of patients with a diagnosis of schizophrenia. PubMed, Scopus, and Google Scholar bibliographic databases were searched with the keywords mentioned below. A total of 555 records were identified. Modern methods of schizophrenia therapy with neuroplastic potential, including neurofeedback, transcranial magnetic stimulation, transcranial direct current stimulation, vagus nerve stimulation, virtual reality therapy, and cognitive remediation therapy, were reviewed and analyzed. Since randomized controlled studies of long-term schizophrenia treatment do not exceed 2-3 years, and the pharmacological treatment itself has an incompletely estimated benefit-risk ratio, treatment methods based on other paradigms, including neuronal self-regulatory and neural plasticity mechanisms, should be considered. Methods available for monitoring neuroplastic effects in vivo (e.g., fMRI, neuropeptides in serum), as well as unfavorable parameters (e.g., features of the metabolic syndrome), enable individualized monitoring of the effectiveness of long-term treatment of schizophrenia.