Changes In Synaptic Strength Research Articles

The fate of neuronal synapse homeostasis in aging, infection, and inflammation.

Neuroplasticity is the brain's ability to reorganize and modify its neuronal connections in response to environmental stimuli, experiences, learning, and disease processes. This encompasses a variety of mechanisms, including changes in synaptic strength and connectivity, the formation of new synapses, alterations in neuronal structure and function, and the generation of new neurons. Proper functioning of synapses, which facilitate neuron-to-neuron communication, is crucial for brain activity. Neuronal synapse homeostasis, which involves regulating and maintaining synaptic strength and function in the central nervous system (CNS), is vital for this process. Disruptions in synaptic balance, due to factors like inflammation, aging, or infection, can lead to impaired brain function. This review highlights the main aspects and mechanisms underlying synaptic homeostasis, particularly in the context of aging, infection, and inflammation.

Cognitive Impairment and Synaptic Dysfunction in Cardiovascular Disorders: The New Frontiers of the Heart-Brain Axis.

Within the central nervous system, synaptic plasticity, fundamental to processes like learning and memory, is largely driven by activity-dependent changes in synaptic strength. This plasticity often manifests as long-term potentiation (LTP) and long-term depression (LTD), which are bidirectional modulations of synaptic efficacy. Strong epidemiological and experimental evidence show that the heart-brain axis could be severely compromised by both neurological and cardiovascular disorders. Particularly, cardiovascular disorders, such as heart failure, hypertension, obesity, diabetes and insulin resistance, and arrhythmias, may lead to cognitive impairment, a condition known as cardiogenic dementia. Herein, we review the available knowledge on the synaptic and molecular mechanisms by which cardiogenic dementia may arise and describe how LTP and/or LTD induction and maintenance may be compromised in the CA1 region of the hippocampus by heart failure, metabolic syndrome, and arrhythmias. We also discuss the emerging evidence that endothelial dysfunction may contribute to directly altering hippocampal LTP by impairing the synaptically induced activation of the endothelial nitric oxide synthase. A better understanding of how CV disorders impact on the proper function of central synapses will shed novel light on the molecular underpinnings of cardiogenic dementia, thereby providing a new perspective for more specific pharmacological treatments.

Neuron-Glial Interactions: Implications for Plasticity, Behavior, and Cognition.

The traditional view of glial cells as mere supportive tissue has shifted, due to advances in technology and theoretical conceptualization, to include a diversity of other functions, such as regulation of complex behaviors. Astrocytes, the most abundant glial cells in the central nervous system (CNS), have been shown to modulate synaptic functions through gliotransmitter-mediated neurotransmitter reuptake, influencing neuronal signaling and behavioral functions. Contemporary studies further highlight astrocytes' involvement in complex cognitive functions. For instance, inhibiting astrocytes in the hippocampus can lead to memory deficits, suggesting their integral role in memory processes. Moreover, astrocytic calcium activity and astrocyte-neuron metabolic coupling have been linked to changes in synaptic strength and learning. Microglia, another type of glial cell, also extend beyond their supportive roles, contributing to learning and memory processes, with microglial reductions impacting these functions in a developmentally dependent manner. Oligodendrocytes, traditionally thought to have limited roles postdevelopment, are now recognized for their activity-dependent modulation of myelination and plasticity, thus influencing behavioral responses. Recent advancements in technology and computational modeling have expanded our understanding of glial functions, particularly how astrocytes influence neuronal circuits and behaviors. This review underscores the importance of glial cells in CNS functions and the need for further research to unravel the complexities of neuron-glia interactions, the impact of these interactions on brain functions, and potential implications for neurological diseases.

Short-term plasticity and context-dependent circuit function: Insights from retinal circuitry

Changes in synaptic strength across timescales are integral to algorithmic operations of neural circuits. However, pinpointing synaptic loci that undergo plasticity in intact brain circuits and delineating contributions of synaptic plasticity to circuit function remain challenging. The whole-mount retina preparation provides an accessible platform for measuring plasticity at specific synapses while monitoring circuit-level behaviors during visual processing ex vivo. In this review, we discuss insights gained from retina studies into the versatile roles of short-term synaptic plasticity in context-dependent circuit functions. Plasticity at single synapse level greatly expands the algorithms of common microcircuit motifs and contributes to diverse circuit-level behaviors such as gain modulation, selective gating, and stimulus-dependent excitatory/inhibitory balance. Examples in retinal circuitry offer unequivocal support that synaptic plasticity increases the computational capacity of hardwired neural circuitry.

Competitive processes shape multi-synapse plasticity along dendritic segments

Neurons receive thousands of inputs onto their dendritic arbour, where individual synapses undergo activity-dependent plasticity. Long-lasting changes in postsynaptic strengths correlate with changes in spine head volume. The magnitude and direction of such structural plasticity - potentiation (sLTP) and depression (sLTD) - depend upon the number and spatial distribution of stimulated synapses. However, how neurons allocate resources to implement synaptic strength changes across space and time amongst neighbouring synapses remains unclear. Here we combined experimental and modelling approaches to explore the elementary processes underlying multi-spine plasticity. We used glutamate uncaging to induce sLTP at varying number of synapses sharing the same dendritic branch, and we built a model incorporating a dual role Ca2+-dependent component that induces spine growth or shrinkage. Our results suggest that competition among spines for molecular resources is a key driver of multi-spine plasticity and that spatial distance between simultaneously stimulated spines impacts the resulting spine dynamics.

Logical Resonance in Izhikevich Neuron

This paper proposes a new logic element model based on an Izhikevich (IZ) neuron and neural system that emulates two- and three-state logic behaviours. In a noise-free environment, with a periodic current of suitable amplitude and frequency, the IZ system is capable of performing logical AND and OR operations. Initially, a single IZ neuron demonstrates membrane dynamics in response to an input signal generated by combining two-state logic currents below the threshold. Subsequently, an IZ neural system model is introduced to enhance the reliability and resilience of the system. This model is characterised by electrical coupling with fast conduction and chemical coupling with a more adaptable structure. Each logic input independently influences each neuron within the system. Additionally, it has been observed that the reliability of the logic element is influenced by changes in synaptic strength, with a neural system lacking sufficient synaptic strength failing to generate logical output. Furthermore, the system displays a three-state logic behaviour under suitable forcing periodicity, thus enhancing the power efficiency of the logic element. The proposed IZ neuron and neural system are expected to significantly impact the development of brain-inspired logic elements.

PI3K couples long-term synaptic potentiation with cofilin recruitment and actin polymerization in dendritic spines via its regulatory subunit p85α

Long-term synaptic plasticity is typically associated with morphological changes in synaptic connections. However, the molecular mechanisms coupling functional and structural aspects of synaptic plasticity are still poorly defined. The catalytic activity of type I phosphoinositide-3-kinase (PI3K) is required for specific forms of synaptic plasticity, such as NMDA receptor-dependent long-term potentiation (LTP) and mGluR-dependent long-term depression (LTD). On the other hand, PI3K signaling has been linked to neuronal growth and synapse formation. Consequently, PI3Ks are promising candidates to coordinate changes in synaptic strength with structural remodeling of synapses. To investigate this issue, we targeted individual regulatory subunits of type I PI3Ks in hippocampal neurons and employed a combination of electrophysiological, biochemical and imaging techniques to assess their role in synaptic plasticity. We found that a particular regulatory isoform, p85α, is selectively required for LTP. This specificity is based on its BH domain, which engages the small GTPases Rac1 and Cdc42, critical regulators of the actin cytoskeleton. Moreover, cofilin, a key regulator of actin dynamics that accumulates in dendritic spines after LTP induction, failed to do so in the absence of p85α or when its BH domain was overexpressed as a dominant negative construct. Finally, in agreement with this convergence on actin regulatory mechanisms, the presence of p85α in the PI3K complex determined the extent of actin polymerization in dendritic spines during LTP. Therefore, this study reveals a molecular mechanism linking structural and functional synaptic plasticity through the coordinate action of PI3K catalytic activity and a specific isoform of the regulatory subunits.

At the onset of active whisking, the input layer of barrel cortex exhibits a 24 h window of increased excitability that depends on prior experience.

The development of motor control over sensory organs is a critical milestone in sensory processing, enabling active exploration and shaping of the sensory environment. However, whether the onset of sensory organ motor control directly influences the development of corresponding sensory cortices remains unknown. Here, we exploit the late onset of whisking behavior in mice to address this question in the somatosensory system. Using ex vivo electrophysiology, we discovered a transient increase in the intrinsic excitability of excitatory neurons in layer IV of the barrel cortex, which processes whisker input, precisely coinciding with the onset of active whisking at postnatal day 14 (P14). This increase in neuronal gain was specific to layer IV, independent of changes in synaptic strength, and required prior sensory experience. Strikingly, the effect was not observed in layer II/III of the barrel cortex or in the visual cortex upon eye opening, suggesting a unique interaction between the development of active sensing and the thalamocortical input layer in the somatosensory system. Predictive modeling indicated that changes in active membrane conductances alone could reliably distinguish P14 neurons in control but not whisker-deprived hemispheres. Our findings demonstrate an experience-dependent, lamina-specific refinement of neuronal excitability tightly linked to the emergence of active whisking. This transient increase in the gain of the thalamic input layer coincides with a critical period for synaptic plasticity in downstream layers, suggesting a role in facilitating cortical maturation and sensory processing. Together, our results provide evidence for a direct interaction between the development of motor control and sensory cortex, offering new insights into the experience-dependent development and refinement of sensory systems. These findings have broad implications for understanding the interplay between motor and sensory development, and how the mechanisms of perception cooperate with behavior.

At the Basis of Brain Malformations: Brain Plasticity, Developmental Neurobiology, and Considerations for Rehabilitation

AbstractFrom early age in the human brain occurs plasticity process that influences its development. The functioning of the brain is governed by its neuronal connectivity and the synaptic dynamics of these connections. A neuron, over thousands of synapses, can receive a large number of inputs and produce different outputs leading to the consolidation and integration of memory. Synaptic plasticity is the set of experience-dependent changes in neuronal pathways that support acquired habits. It is the ability of the nervous system to reshape connectivity between neurons, changing the functional and structural organization of neuronal circuits that allows us to adapt to the multiple and continuous changes in the environment and leading to processes such as cognitive development and the ability to learn. Synaptic plasticity is mainly due to short- and long-term mechanisms. Short-term synaptic plasticity refers to changes in synaptic strength that occurs very quickly (from one-thousandth of a second to 5 minutes) and are temporary and decay over minutes (maximum 30 minutes). Long-term synaptic plasticity is defined by a long-lasting, activity-dependent change in synaptic efficacy, last from hours up to a lifetime (from 30 minutes to weeks, months, and years) and is thought to constitute the basis of learning and memory. A significant difference occurs in the nature of the change; short-term plasticity adds only a functional change, whereas long-term plasticity causes not only functional but also structural changes. Aside from genetic factors and metabolic processes, brain development is mediated also by environmental factors. Interaction with the environment plays a key role in the development and growth of neural networks and neuroplasticity. Environmental interactions that can modify and increase the development of neural networks and intelligence in children are several and are herein discussed.

Mesoscale simulations predict the role of synergistic cerebellar plasticity during classical eyeblink conditioning.

According to the motor learning theory by Albus and Ito, synaptic depression at the parallel fibre to Purkinje cells synapse (pf-PC) is the main substrate responsible for learning sensorimotor contingencies under climbing fibre control. However, recent experimental evidence challenges this relatively monopolistic view of cerebellar learning. Bidirectional plasticity appears crucial for learning, in which different microzones can undergo opposite changes of synaptic strength (e.g. downbound microzones-more likely depression, upbound microzones-more likely potentiation), and multiple forms of plasticity have been identified, distributed over different cerebellar circuit synapses. Here, we have simulated classical eyeblink conditioning (CEBC) using an advanced spiking cerebellar model embedding downbound and upbound modules that are subject to multiple plasticity rules. Simulations indicate that synaptic plasticity regulates the cascade of precise spiking patterns spreading throughout the cerebellar cortex and cerebellar nuclei. CEBC was supported by plasticity at the pf-PC synapses as well as at the synapses of the molecular layer interneurons (MLIs), but only the combined switch-off of both sites of plasticity compromised learning significantly. By differentially engaging climbing fibre information and related forms of synaptic plasticity, both microzones contributed to generate a well-timed conditioned response, but it was the downbound module that played the major role in this process. The outcomes of our simulations closely align with the behavioural and electrophysiological phenotypes of mutant mice suffering from cell-specific mutations that affect processing of their PC and/or MLI synapses. Our data highlight that a synergy of bidirectional plasticity rules distributed across the cerebellum can facilitate finetuning of adaptive associative behaviours at a high spatiotemporal resolution.

Axon morphology and intrinsic cellular properties determine repetitive transcranial magnetic stimulation threshold for plasticity.

Repetitive transcranial magnetic stimulation (rTMS) is a widely used therapeutic tool in neurology and psychiatry, but its cellular and molecular mechanisms are not fully understood. Standardizing stimulus parameters, specifically electric field strength, is crucial in experimental and clinical settings. It enables meaningful comparisons across studies and facilitates the translation of findings into clinical practice. However, the impact of biophysical properties inherent to the stimulated neurons and networks on the outcome of rTMS protocols remains not well understood. Consequently, achieving standardization of biological effects across different brain regions and subjects poses a significant challenge. This study compared the effects of 10 Hz repetitive magnetic stimulation (rMS) in entorhino-hippocampal tissue cultures from mice and rats, providing insights into the impact of the same stimulation protocol on similar neuronal networks under standardized conditions. We observed the previously described plastic changes in excitatory and inhibitory synaptic strength of CA1 pyramidal neurons in both mouse and rat tissue cultures, but a higher stimulation intensity was required for the induction of rMS-induced synaptic plasticity in rat tissue cultures. Through systematic comparison of neuronal structural and functional properties and computational modeling, we found that morphological parameters of CA1 pyramidal neurons alone are insufficient to explain the observed differences between the groups. Although morphologies of mouse and rat CA1 neurons showed no significant differences, simulations confirmed that axon morphologies significantly influence individual cell activation thresholds. Notably, differences in intrinsic cellular properties were sufficient to account for the 10% higher intensity required for the induction of synaptic plasticity in the rat tissue cultures. These findings demonstrate the critical importance of axon morphology and intrinsic cellular properties in predicting the plasticity effects of rTMS, carrying valuable implications for the development of computer models aimed at predicting and standardizing the biological effects of rTMS.

Stability against fluctuations: a two-dimensional study of scaling, bifurcations and spontaneous symmetry breaking in stochastic models of synaptic plasticity

Stochastic models of synaptic plasticity must confront the corrosive influence of fluctuations in synaptic strength on patterns of synaptic connectivity. To solve this problem, we have proposed that synapses act as filters, integrating plasticity induction signals and expressing changes in synaptic strength only upon reaching filter threshold. Our earlier analytical study calculated the lifetimes of quasi-stable patterns of synaptic connectivity with synaptic filtering. We showed that the plasticity step size in a stochastic model of spike-timing-dependent plasticity (STDP) acts as a temperature-like parameter, exhibiting a critical value below which neuronal structure formation occurs. The filter threshold scales this temperature-like parameter downwards, cooling the dynamics and enhancing stability. A key step in this calculation was a resetting approximation, essentially reducing the dynamics to one-dimensional processes. Here, we revisit our earlier study to examine this resetting approximation, with the aim of understanding in detail why it works so well by comparing it, and a simpler approximation, to the system’s full dynamics consisting of various embedded two-dimensional processes without resetting. Comparing the full system to the simpler approximation, to our original resetting approximation, and to a one-afferent system, we show that their equilibrium distributions of synaptic strengths and critical plasticity step sizes are all qualitatively similar, and increasingly quantitatively similar as the filter threshold increases. This increasing similarity is due to the decorrelation in changes in synaptic strength between different afferents caused by our STDP model, and the amplification of this decorrelation with larger synaptic filters.

Neuroplasticity in the pathogenesis and treatment of chronic pain syndrome: new research and therapeutic perspectives

Recent research and therapeutic outlooks examine the impact of neuroplasticity on the progression and management of chronic pain syndrome. Aims: To review neurobiological basis as well as neuroplastic mechanisms in chronic pain syndrome, exploring bidirectional relationship and innovative therapies and to evaluate efficacy/safety of diverse treatments like TENS, rTMS, pharmacotherapies, and exercise in chronic pain management. Study design: A narrative literature review. Place and Duration of Study: 2019 to 2024. Methodology: A narrative review was conducted using the keywords “Neuroplasticity" AND "Chronic Pain" on PubMed yielded a total of 333 publications. Out of the total publications, 21 were deemed directly relevant, probably providing valuable perspectives on the link between neuroplasticity and chronic pain. Results: Results showed that out of the 11 studies analysed, 7 investigated the bidirectional relationship between chronic pain and neuroplasticity. Additionally, 4 studies reviewed pharmacological methods, 2 studies discussed personalised management and mechanistic profiling, and 7 explored neuromodulation and non-pharmacological interventions. Various neurophysiological correlates of chronic pain were studied, including somatosensory and cortical neurophysiology profiles but Central sensitisation and neuroinflammation were the explored key mechanisms. Activity-dependent plasticity, neuroplasticity in pain modulation, and cortical plasticity are extensively explored, revealing changes in neural activity, synaptic strength, and brain structure. Research explores the connection between chronic pain and neuroplasticity, examining how they impact each other and highlighting the constant interaction between pain perception and neural plasticity. Innovative therapeutic strategies include neuromodulation techniques, pharmacological interventions, personalised pain management, and multimodal approach. Non-invasive brain stimulation, transcutaneous electrical nerve stimulation , and home-based focused tDCS show promise in chronic pain management. Conclusion: In summary, these findings highlighted the multifaceted nature of chronic pain and the on-going efforts to develop effective therapeutic interventions, showcasing a dynamic field of research aiming to improve the lives of those suffering from chronic pain.

Dynamic Network Connectivity: from monkeys to humans.

Human brain imaging research using functional MRI (fMRI) has uncovered flexible variations in the functional connectivity between brain regions. While some of this variability likely arises from the pattern of information flow through circuits, it may also be influenced by rapid changes in effective synaptic strength at the molecular level, a phenomenon called Dynamic Network Connectivity (DNC) discovered in non-human primate circuits. These neuromodulatory molecular mechanisms are found in layer III of the macaque dorsolateral prefrontal cortex (dlPFC), the site of the microcircuits shown by Goldman-Rakic to be critical for working memory. This research has shown that the neuromodulators acetylcholine, norepinephrine, and dopamine can rapidly change the strength of synaptic connections in layer III dlPFC by (1) modifying the depolarization state of the post-synaptic density needed for NMDA receptor neurotransmission and (2) altering the open state of nearby potassium channels to rapidly weaken or strengthen synaptic efficacy and the strength of persistent neuronal firing. Many of these actions involve increased cAMP-calcium signaling in dendritic spines, where varying levels can coordinate the arousal state with the cognitive state. The current review examines the hypothesis that some of the dynamic changes in correlative strength between cortical regions observed in human fMRI studies may arise from these molecular underpinnings, as has been seen when pharmacological agents or genetic alterations alter the functional connectivity of the dlPFC consistent with the macaque physiology. These DNC mechanisms provide essential flexibility but may also confer vulnerability to malfunction when dysregulated in cognitive disorders.

Exploring the Role of Neuroplasticity in Development, Aging, and Neurodegeneration.

Neuroplasticity refers to the ability of the brain to reorganize and modify its neural connections in response to environmental stimuli, experience, learning, injury, and disease processes. It encompasses a range of mechanisms, including changes in synaptic strength and connectivity, the formation of new synapses, alterations in the structure and function of neurons, and the generation of new neurons. Neuroplasticity plays a crucial role in developing and maintaining brain function, including learning and memory, as well as in recovery from brain injury and adaptation to environmental changes. In this review, we explore the vast potential of neuroplasticity in various aspects of brain function across the lifespan and in the context of disease. Changes in the aging brain and the significance of neuroplasticity in maintaining cognitive function later in life will also be reviewed. Finally, we will discuss common mechanisms associated with age-related neurodegenerative processes (including protein aggregation and accumulation, mitochondrial dysfunction, oxidative stress, and neuroinflammation) and how these processes can be mitigated, at least partially, by non-invasive and non-pharmacologic lifestyle interventions aimed at promoting and harnessing neuroplasticity.

Synaptic plasticity and the role of astrocytes in central metabolic circuits.

Neural circuits in the brain, primarily in the hypothalamus, are paramount to the homeostatic control of feeding and energy utilization. They integrate hunger, satiety, and body adiposity cues from the periphery and mediate the appropriate behavioral and physiological responses to satisfy the energy demands of the animal. Notably, perturbations in central homeostatic circuits have been linked to the etiology of excessive feeding and obesity. Considering the ever-changing energy requirements of the animal and required adaptations, it is not surprising that brain-feeding circuits remain plastic in adulthood and are subject to changes in synaptic strength as a consequence of nutritional status. Indeed, synapse density, probability of presynaptic transmitter release, and postsynaptic responses in hypothalamic energy balance centers are tailored to behavioral and physiological responses required to sustain survival. Mounting evidence supports key roles of astrocytes facilitating some of this plasticity. Here we discuss these synaptic plasticity mechanisms and the emerging roles of astrocytes influencing energy and glucose balance control in health and disease. This article is categorized under: Cancer > Molecular and Cellular Physiology Neurological Diseases > Molecular and Cellular Physiology.

Homosynaptic plasticity induction causes heterosynaptic changes at the unstimulated neighbors in an induction pattern and location-specific manner.

Dendritic spines are highly dynamic structures whose structural and functional fluctuations depend on multiple factors. Changes in synaptic strength are not limited to synapses directly involved in specific activity patterns. Unstimulated clusters of neighboring spines in and around the site of stimulation can also undergo alterations in strength. Usually, when plasticity is induced at single dendritic spines with glutamate uncaging, neighboring spines do not show any significant structural fluctuations. Here, using two-photon imaging and glutamate uncaging at single dendritic spines of hippocampal pyramidal neurons, we show that structural modifications at unstimulated neighboring spines occur and are a function of the temporal pattern of the plasticity-inducing stimulus. Further, the relative location of the unstimulated neighbors within the local dendritic segment correlates with the extent of heterosynaptic plasticity that is observed. These findings indicate that naturalistic patterns of activity at single spines can shape plasticity at nearby clusters of synapses, and may play a role in priming local inputs for further modifications.

Golgi satellites are essential for polysialylation of NCAM and expression of LTP at distal synapses

The complex cytoarchitecture of neurons poses significant challenges for the maturation of synaptic membrane proteins. It is currently unclear whether locally secreted synaptic proteins bypass the Golgi or whether they traffic through Golgi satellites (GSs). Here, we create a transgenic GS reporter mouse line and show that GSs are widely distributed along dendrites and are capable of mature glycosylation, in particular sialylation. We find that polysialylation of locally secreted NCAM takes place at GSs. Accordingly, in mice lacking a component of trans-Golgi network-to-plasma membrane trafficking, we find fewer GSs and significantly reduced PSA-NCAM levels in distal dendrites of CA1 neurons that receive input from the temporoammonic pathway. Induction of long-term potentiation at those, but not more proximal, synapses is severely impaired. We conclude that GSs serve the need for local mature glycosylation of synaptic membrane proteins in distal dendrites and thereby contribute to rapid changes in synaptic strength.

Anesthetics inhibit phosphorylation of the ribosomal protein S6 in mouse cultured cortical cells and developing brain.

The development and maintenance of neural circuits is highly sensitive to neural activity. General anesthetics have profound effects on neural activity and, as such, there is concern that these agents may alter cellular integrity and interfere with brain wiring, such as when exposure occurs during the vulnerable period of brain development. Under those conditions, exposure to anesthetics in clinical use today causes changes in synaptic strength and number, widespread apoptosis, and long-lasting cognitive impairment in a variety of animal models. Remarkably, most anesthetics produce these effects despite having differing receptor mechanisms of action. We hypothesized that anesthetic agents mediate these effects by inducing a shared signaling pathway. We exposed cultured cortical cells to propofol, etomidate, or dexmedetomidine and assessed the protein levels of dozens of signaling molecules and post-translational modifications using reverse phase protein arrays. To probe the role of neural activity, we performed separate control experiments to alter neural activity with non-anesthetics. Having identified anesthetic-induced changes in vitro, we investigated expression of the target proteins in the cortex of sevoflurane anesthetized postnatal day 7 mice by Western blotting. All the anesthetic agents tested in vitro reduced phosphorylation of the ribosomal protein S6, an important member of the mTOR signaling pathway. We found a comparable decrease in cortical S6 phosphorylation by Western blotting in sevoflurane anesthetized neonatal mice. Using a systems approach, we determined that propofol, etomidate, dexmedetomidine, and APV/TTX all similarly modulate a signaling module that includes pS6 and other cell mediators of the mTOR-signaling pathway. Reduction in S6 phosphorylation and subsequent suppression of the mTOR pathway may be a common and novel signaling event that mediates the impact of general anesthetics on neural circuit development.

Spike timing-dependent plasticity alters electrosensory neuron synaptic strength in vitro but does not consistently predict changes in sensory tuning in vivo.

How do sensory systems optimize detection of behaviorally relevant stimuli when the sensory environment is constantly changing? We addressed the role of spike timing-dependent plasticity (STDP) in driving changes in synaptic strength in a sensory pathway and whether those changes in synaptic strength could alter sensory tuning. It is challenging to precisely control temporal patterns of synaptic activity in vivo and replicate those patterns in vitro in behaviorally relevant ways. This makes it difficult to make connections between STDP-induced changes in synaptic physiology and plasticity in sensory systems. Using the mormyrid species Brevimyrus niger and Brienomyrus brachyistius, which produce electric organ discharges for electrolocation and communication, we can precisely control the timing of synaptic input in vivo and replicate these same temporal patterns of synaptic input in vitro. In central electrosensory neurons in the electric communication pathway, using whole cell intracellular recordings in vitro, we paired presynaptic input with postsynaptic spiking at different delays. Using whole cell intracellular recordings in awake, behaving fish, we paired sensory stimulation with postsynaptic spiking using the same delays. We found that Hebbian STDP predictably alters sensory tuning in vitro and is mediated by NMDA receptors. However, the change in synaptic responses induced by sensory stimulation in vivo did not adhere to the direction predicted by the STDP observed in vitro. Further analysis suggests that this difference is influenced by polysynaptic activity, including inhibitory interneurons. Our findings suggest that STDP rules operating at identified synapses may not drive predictable changes in sensory responses at the circuit level.NEW & NOTEWORTHY We replicated behaviorally relevant temporal patterns of synaptic activity in vitro and used the same patterns during sensory stimulation in vivo. There was a Hebbian spike timing-dependent plasticity (STDP) pattern in vitro, but sensory responses in vivo did not shift according to STDP predictions. Analysis suggests that this disparity is influenced by differences in polysynaptic activity, including inhibitory interneurons. These results suggest that STDP rules at synapses in vitro do not necessarily apply to circuits in vivo.