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        <title>Frontiers in Synaptic Neuroscience | New and Recent Articles</title>
        <link>https://www.frontiersin.org/journals/synaptic-neuroscience</link>
        <description>RSS Feed for Frontiers in Synaptic Neuroscience | New and Recent Articles</description>
        <language>en-us</language>
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        <pubDate>2026-05-12T19:02:21.167+00:00</pubDate>
        <ttl>60</ttl>
        <item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fnsyn.2026.1819500</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fnsyn.2026.1819500</link>
        <title><![CDATA[Tuning excitatory input to fast-spiking parvalbumin-positive interneurons: a lever for plasticity and hyperexcitability across the lifespan]]></title>
        <pubdate>2026-04-24T00:00:00Z</pubdate>
        <category>Perspective</category>
        <author>Daniel Severin</author><author>Alfredo Kirkwood</author>
        <description><![CDATA[Experience reshapes cortical circuits, yet plasticity is tightly gated—high during early critical periods and increasingly constrained with maturation. Later in life, aging and Alzheimer’s disease (AD) create a growing demand to restrain network hyperactivity. Across these contexts, excitatory drive onto parvalbumin-positive fast-spiking interneurons (PVs)—shaped by synaptic organizers such as NPTX2—offers a control point for tuning inhibitory tone while preserving fast, precise inhibition. We outline the cellular and synaptic specializations that make PVs powerful regulators of network excitability, then synthesize evidence from visual cortex suggesting that critical period termination reflects the loss of plasticity at principal neuron→PV inputs. Finally, we extend this framework to aging and AD, where medial temporal lobe hyperactivity and early PV dysfunction coincide with NPTX2 dysregulation, suggesting that restoring excitatory recruitment of PVs may help stabilize circuits and prevent cognitive decline.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fnsyn.2026.1830809</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fnsyn.2026.1830809</link>
        <title><![CDATA[Metabolic regulation of synaptic plasticity in anorexia nervosa]]></title>
        <pubdate>2026-04-22T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Olof Lagerlöf</author><author>Qiongxuan Lu</author><author>Manish Bhattacharjee</author><author>Rashmi Arora</author><author>Linkun Han</author><author>Jingyu Pan</author><author>Sabrina Galizia</author><author>Peter Asellus</author><author>Erik Ekbäck</author>
        <description><![CDATA[Anorexia nervosa (AN) is increasingly understood as a metabo-psychiatric disorder in which metabolic biology and neural circuit function are intrinsically intertwined. Genetic studies reveal that AN is associated with heritable metabolic traits suggesting that metabolic vulnerability contributes to the disorder. The metabolic profile of AN further shapes brain responses; endocrine signals such as insulin, leptin, ghrelin, and adiponectin elicit atypical neural responses in circuits regulating appetite, reward, interoception, and cognitive control. This altered signaling is accompanied by circuit-specific remodeling, suggesting that the chronic metabolic dysregulation seen in AN affects synaptic plasticity across distributed brain regions. Neural systems that integrate metabolic, emotional, and cognitive information—including hypothalamic, striatal, prefrontal, and limbic circuits—show altered plasticity under starvation. Glucose and insulin modulate excitatory–inhibitory balance and synaptic efficacy, while ketone bodies act as starvation-associated neuromodulators influencing transmitter release and structural plasticity. These and other body-to-brain signals recalibrate network dynamics central to food intake, motivation, and learning. At the molecular level, intracellular metabolic sensors such as AMPK, mTOR, and O-GlcNAc function as transducers that convert nutrient availability into changes in protein synthesis, receptor trafficking, and dendritic spine architecture, providing mechanistic links between metabolic state and synaptic remodeling. Overall, converging evidence supports a model in which AN arises from interactions between metabolic traits and the plastic neural circuits mediating food intake, emotion, and cognition. By clarifying how metabolic signals reshape synaptic ensembles in AN, we present a framework for understanding mechanisms of vulnerability and identify targets capable of restoring adaptive plasticity. This review suggests a trajectory in which treatments jointly address metabolic physiology and brain-based processes of learning, motivation, and affect.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fnsyn.2026.1730181</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fnsyn.2026.1730181</link>
        <title><![CDATA[Patterned pre-sensory spontaneous activity drives the structural refinement of developing cochlear ribbon synapses]]></title>
        <pubdate>2026-03-23T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Victoria C. Halim</author><author>Lukas Hallbrucker</author><author>Jan F. Ahrend</author><author>Cristian Setz</author><author>Roos A. Voorn</author><author>Samira Franke</author><author>Vanessa Konrad</author><author>Alina Seiler</author><author>Tina Pangršič</author><author>Stefan Roesler</author><author>Christian Vogl</author>
        <description><![CDATA[IntroductionIn the mammalian cochlea, hearing relies on highly specialized ribbon-type synapses between sensory inner hair cells (IHCs) and postsynaptic spiral ganglion neurons. During early postnatal maturation, structural and functional refinements re-shape synaptic morphology and thereby maximize release efficiency in the run-up to hearing onset. This developmental period is further characterized by the occurrence of pre-sensory spontaneous activity waves, which are essential for the functional maturation of the ascending auditory pathway– yet, their importance for IHC presynaptic structural refinement remains uncertain.MethodsTo investigate activity-dependent structural plasticity at cochlear ribbon synapses, we combined genetic, pharmacological, and optogenetic approaches with immunohistochemical and electrophysiological analyses. Moreover, we developed a novel optical stimulation device (OSD) that enables millisecond-precise, long-term and differentially-patterned optogenetic activation of cochlear IHCs under tightly controlled conditions within a standard tissue culture incubator.ResultsUsing this experimental framework, we show that positive as well as negative activity modulation triggers dynamic and rapidly-inducible homeostatic scaling of ribbon synapse morphology. Moreover, our data indicate that the temporal pattern of the presynaptic activity acts as a fundamental regulatory component of this process.DiscussionOur results suggest that – prior to hearing onset – pre-sensory synaptic activity plays a critical role in shaping cochlear ribbon synapse architecture in the developing auditory system.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fnsyn.2026.1771781</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fnsyn.2026.1771781</link>
        <title><![CDATA[The Freiburg framework for multimodal ex situ assessment of neural plasticity in human cortical tissue]]></title>
        <pubdate>2026-03-16T00:00:00Z</pubdate>
        <category>Perspective</category>
        <author>Jakob Straehle</author><author>Christos Galanis</author><author>Lukas Grünewald</author><author>Elli-Anna Balta</author><author>Tobias D. Deller</author><author>Ute Häussler</author><author>Boris Mizaikoff</author><author>Jürgen Beck</author><author>Andreas Vlachos</author>
        <description><![CDATA[Studying human cortical physiology requires access to viable brain tissue, yet species-specific differences limit the translational value of animal models. To address this, multiple laboratories have developed ex situ approaches for investigating neurosurgical access tissue using electrophysiological, molecular, and imaging techniques. Here, we introduce the Freiburg framework—a structured, multimodal approach that integrates high-resolution electrophysiology, advanced imaging, molecular analyses, and Raman microscopy to assess neuronal and glial function under controlled, near-native conditions. Clinical metadata, including preoperative MRI, together with in-patient controls is systematically incorporated to account for biological variability and to enable human-to-human translational (H2H) comparisons. The framework further enables controlled neuromodulatory and pharmacological interventions, including ex situ repetitive transcranial magnetic stimulation (rTMS). By formalizing an end-to-end experimental pipeline, the Freiburg framework supports systematic investigation of human-specific neurophysiological mechanisms and provides a robust foundation for translational human neuroscience.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fnsyn.2026.1798456</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fnsyn.2026.1798456</link>
        <title><![CDATA[Rhythmic network activity in human brain slices: variability, mechanisms, and translational insights]]></title>
        <pubdate>2026-03-09T00:00:00Z</pubdate>
        <category>Mini Review</category>
        <author>Danqing Yang</author><author>Dirk Feldmeyer</author>
        <description><![CDATA[In vitro maintained human brain slices provide a unique experimental platform for investigating rhythmic neuronal network activity, bridging the gap between animal models and clinical studies. A wide range of spontaneous and induced oscillatory activities has been described in human brain slices. However, their occurrence and characteristics are strongly shaped by methodological determinants spanning tissue origin, slice preparation, recording conditions, and induction strategies. This has been shown to have a profound impact on the reproducibility and interpretation of oscillatory dynamics. This review synthesizes current evidence on rhythmic network activity in acute human brain slices, with a particular emphasis on how methodological determinants interact with intrinsic circuit properties to generate oscillatory dynamics. We discuss how different experimental manipulations influence oscillation frequency, stability, and spatial organization. We further examine the cellular and circuit mechanisms underlying rhythmic activity, highlighting the roles of excitatory–inhibitory balance, synaptic dynamics, neuromodulatory influences, and distinct interneuron populations. Finally, we consider how oscillatory patterns differ across disease contexts, particularly epilepsy and tumor-associated cortex, and discuss the translational value and limitations of human brain slices for linking microcircuit mechanisms to pathological and functional brain states.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fnsyn.2026.1741328</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fnsyn.2026.1741328</link>
        <title><![CDATA[Increased synaptic turnover in injured cortical axons: exploring the role of SARM1 ablation]]></title>
        <pubdate>2026-02-23T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Ensieh Izadi</author><author>William Bennett</author><author>Jessica Collins</author><author>Aidan Bindoff</author><author>Anna King</author><author>Alison Canty</author>
        <description><![CDATA[IntroductionProgrammed axon degeneration significantly affects neural connectivity, however, the underlying mechanisms remain poorly understood, particularly in cortical regions. Sterile Alpha and TIR motif-containing protein 1 (SARM1) is a known regulator of axon degeneration in the peripheral nervous system, but its role in cortical axon plasticity, particularly during injury conditions, remains unclear. This study examined the role of SARM1 in synaptic connectivity and remodelling in the adult sensory-motor cortex under normal physiological conditions and following acute axonal injury.MethodsAdult male Thy1-GFP-M mice (3–12 months) expressing EGFP in excitatory neurons were also either wild-type (WT-GFP) or null for SARM1 (SARM1KO-GFP). Using in vivo multiphoton microscopy, long cortical axon segments (~335 μm ± 140 μm), with terminaux and en passant synaptic boutons in the upper layers of the cortical neuropil, were repeatedly imaged at 48-h intervals to assess axon morphology, synaptic density, and synaptic turnover in the presence and absence of SARM1.ResultsWithout injury, axon morphology, synaptic density, and turnover were similar between WT and SARM1KO groups, suggesting that SARM1 is not necessary for maintaining baseline cortical synaptic connectivity. Following axotomy by laser lesion, the non-degenerating proximal axon (still connected to the soma) showed significant changes in synaptic plasticity, with an increased rate of loss of synapses.DiscussionOur findings suggest that SARM1 plays no role in the remodelling of synapses in the proximal axon after an acute axonal injury.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fnsyn.2026.1770193</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fnsyn.2026.1770193</link>
        <title><![CDATA[Enhanced information processing in the human neocortex: cellular mechanisms and translational perspectives]]></title>
        <pubdate>2026-02-13T00:00:00Z</pubdate>
        <category>Mini Review</category>
        <author>Manuela Tore</author><author>Laura Monni</author><author>Alessio Di Clemente</author><author>Michele Giugliano</author>
        <description><![CDATA[Understanding the sophisticated cognitive abilities of the human brain requires understanding its cellular and synaptic components. While rodent studies provide foundational knowledge, recent research using freshly resected human neocortical and hippocampal tissue has revealed unanticipated distinctive cellular characteristics. These properties, identified through in vitro electrophysiology, anatomical reconstructions, and computational modeling, have profound implications for physiological processes and modulatory responses. Here we highlight and review a selection of key unique features of human neurons. Human layer 2/3 pyramidal cells exhibit exceptionally low specific membrane capacitance and distinctive ion channel kinetics. Moreover, human pyramidal-to-pyramidal connections display species-specific synaptic dynamics, recovering from short-term depression much faster than in rodents. We also highlight that human pyramidal neurons exhibit more elaborate dendritic trees, particularly perisomatic branching, and faster, more stable Action Potentials (AP) dynamics. Interestingly, these features allow higher-bandwidth information transfer, reflecting enhanced computational power. All these cell-level differences directly impact how circuits process information and respond to pharmacological interventions. Increasingly, drugs targeting ion channels or synaptic mechanisms are used but often display different efficacy or kinetics in human neurons compared to rodents, reflecting underlying biophysical disparities. Consequently, leveraging human brain tissue is key as it allows for the identification of human-specific drug targets and a more accurate understanding of disease mechanisms. This review highlights these crucial cellular distinctions and underscores the importance of exploiting resected human brain tissue for advancing central nervous system therapeutics.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fnsyn.2026.1766413</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fnsyn.2026.1766413</link>
        <title><![CDATA[Group I metabotropic glutamate receptors differentially modulate excitatory transmission across interneuron types in the human cortex]]></title>
        <pubdate>2026-02-13T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Joanna Grace Sandle</author><author>Gábor Molnár</author><author>Martin Tóth</author><author>Katalin Ágnes Kocsis</author><author>Éva Adrienn Csajbók</author><author>Pál Barzó</author><author>Karri Lamsa</author><author>Gábor Tamás</author>
        <description><![CDATA[IntroductionGroup I metabotropic glutamate receptors (mGluRs) play a critical role in regulating neuronal excitability, synaptic strength, and cortical network activity. Although their physiological functions and involvement in neurological disorders are well established, direct experimental evidence for their role in human cortical neurons remains limited.MethodsWe investigated the effects of group I mGluR activation on excitatory synaptic transmission in the human supragranular cortex using paired whole-cell patch-clamp recordings from synaptically connected pyramidal cells and interneurons in acute slices of human neocortex resected during neurosurgery.ResultsActivation of mGluRs with the agonist (S)-3,5-dihydroxyphenylglycine (DHPG) altered excitatory synaptic efficacy in an interneuron subtype–dependent manner. Specifically, we observed acute enhancement of excitatory postsynaptic current (EPSC) amplitudes in 54% of fast-spiking interneurons and in 15% of non-fast-spiking interneuron types. Applying the same experimental protocol in slices from Wistar rats resulted in a similar increase in synaptic strength in fast-spiking interneurons. However, paired-pulse ratio analysis showed species-dependent differences, which may reflect distinct contributions of pre- and postsynaptic factors to the observed modulation.DiscussionTogether, these results demonstrate that acute modulation of pyramidal cell–fast-spiking interneuron synapses via group I mGluRs is conserved between human and rodent neocortex, while pointing to species-specific underlying mechanisms. Moreover, mGluR-mediated modulation exhibits cell-type specificity in human cortical circuits. Collectively, these findings provide direct functional evidence for group I mGluR-dependent synaptic regulation in the human cortex and highlight important species- and cell-type–specific differences that should be considered when extrapolating rodent data to human cortical physiology and disease mechanisms.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fnsyn.2026.1769881</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fnsyn.2026.1769881</link>
        <title><![CDATA[Spatial characterization of backpropagating action potential-evoked Ca2+ signals in human cortical layer 2/3 pyramidal neurons]]></title>
        <pubdate>2026-02-10T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Ildikó Szöts</author><author>Martin Tóth</author><author>Csongor Ludányi</author><author>Pál Barzó</author><author>Éva Adrienn Csajbók</author><author>Gábor Tamás</author><author>Gábor Molnár</author>
        <description><![CDATA[IntroductionIn pyramidal neurons, backpropagating action potentials (bAPs) activate voltage-gated calcium channels (VGCCs), producing compartment-specific dendritic Ca2+ transients. While extensively characterized in rodent models, little is known about the spatial properties and channel-specific contributions of bAP-induced Ca2+ signals in human cortical neurons.MethodsWe used simultaneous whole-cell patch-clamp recordings and two-photon Ca2+ imaging in acute human cortical slices to characterize bAP-evoked Ca2+ transients along the apical dendrites of layer 2/3 pyramidal neurons.ResultsWe found that Ca2+ signal amplitudes followed a non-linear spatial profile, increasing proximally and peaking between 50-100 µm from the soma before declining in more distal regions. Oblique dendrites exhibited significantly higher Ca2+ amplitudes compared to the primary apical branches. Morphological parameters, such as dendritic diameter, spine density, and branching, were correlated with the spatial profile of Ca2+ transients to the peak of the calcium signal profile. Pharmacological blockade of VGCCs revealed that major channel subtypes (L-, N-, R-, and T-type) contribute to dendritic Ca2+ influx, with distinct spatial effects. In particular, N-type channel blockade produced the largest attenuation in the medial dendritic segments, while T-type channel inhibition affected all regions.DiscussionThese findings highlight spatial heterogeneity and channel-specific contributions to dendritic Ca2+ signaling in human neocortical neurons and underscore the influence of dendritic morphology on signal propagation.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fnsyn.2026.1761008</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fnsyn.2026.1761008</link>
        <title><![CDATA[Convergence and divergence of molecular mechanisms in Hebbian and homeostatic plasticity]]></title>
        <pubdate>2026-02-09T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Kira M. Feighan</author><author>Harshit K. Thakare</author><author>Stephen D. Glasgow</author><author>Timothy E. Kennedy</author>
        <description><![CDATA[The umbrella of synaptic plasticity includes associative, activity-dependent alterations in synaptic strength that are thought to underlie learning and memory, and negative feedback that stabilizes network activity, termed Hebbian and homeostatic plasticity, respectively. These forms of plasticity respond to activity oppositely, and on different spatial and temporal scales. However, despite these fundamental differences, many similar molecular mechanisms are engaged by each form of plasticity to alter synaptic strength. Here, we review molecular mechanisms involved in homeostatic plasticity and compare their involvement in Hebbian plasticity. We focus on synaptic scaling, long-term potentiation, and long-term depression, which are mediated by regulation of post-synaptic amino-3-hydroxyl-5-methyl-4-isoxazole-propionate-type glutamate receptor (AMPARs) accumulation. Addressing synaptic scaffolding, intracellular signaling, cell-adhesion, and secreted factors, we identify mechanisms that appear to be convergent, differentially engaged, and divergent that uniquely regulate homeostatic scaling. These comparisons identify clear gaps to be addressed by future studies that aim to parse the contributions of Hebbian and homeostatic plasticity to regulate AMPAR function.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fnsyn.2026.1741452</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fnsyn.2026.1741452</link>
        <title><![CDATA[Evolutionary neuroeconomic adaptations of fast-spiking neurons in the human neocortex]]></title>
        <pubdate>2026-01-16T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Viktor Szegedi</author><author>Abdennour Douida</author><author>Gábor Hutóczki</author><author>László Novák</author><author>Karri Lamsa</author>
        <description><![CDATA[Homo sapiens has evolved a large and complex neocortex that underlies advanced cognitive capabilities. Neural computation, however, is inherently energy-intensive, and evolutionary pressures have shaped mechanisms that optimize both computational performance and energy efficiency in the human brain. Fast-spiking interneurons, particularly basket cells, are among the most active neuron types in the neocortex, where they play a key role in coordinating time and space in the activity of neuronal networks, but their high activity levels require high metabolic resources. Because the human neocortex is significantly larger than that of rodents—and contains a higher proportion of inhibitory interneurons relative to pyramidal cells—this expansion may have created evolutionary pressure to reduce the energetic cost of fast-spiking neurons. Compared with rodents, human fast-spiking neurons exhibit adaptations that appear to lower energy expenditure while preserving rapid and precise inhibition. One such adaptation is increased input resistance, which allows both excitation and inhibition to occur with reduced transmembrane ion currents, thereby decreasing the energy required to maintain ionic gradients across the plasma membrane. Since higher input resistance also slows down membrane potential changes, these cells show secondary adaptations that maintain rapid electrical signaling. Additional modifications—such as optimized ion channel composition in soma and axon initial segment, enhanced axon myelination, simplified structure of dendritic tree, and multivesicular synapses—further improve electrical signaling and are likely to reduce metabolic demand, collectively reducing ATP consumption in the neuronal network. By integrating cellular and synaptic perspectives, this review highlights how fast-spiking neurons in the human neocortex have evolved differently from those in rodents to balance energy efficiency while maintaining computational power, providing insight into the metabolic constraints of the human brain.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fnsyn.2025.1676317</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fnsyn.2025.1676317</link>
        <title><![CDATA[Aging and Alzheimer’s: the critical role of mitochondrial dysfunction and synaptic alterations]]></title>
        <pubdate>2026-01-02T00:00:00Z</pubdate>
        <category>Review</category>
        <author> Pinky</author><author>Zitin Wali</author><author> Neha</author><author>Prachi Tiwari</author><author>Mohamed El-Tanani</author><author>Syed Arman Rabbani</author><author>Suhel Parvez</author>
        <description><![CDATA[Alzheimer’s disease is a progressive neurodegenerative disorder marked by cognitive decline, accumulation of amyloid-β plaques and neurofibrillary tangles, synaptic dysfunction, and mitochondrial impairment. Despite multiple therapeutic strategies, currently available treatments only provide symptomatic relief without halting disease progression. Emerging evidence implicates mitochondrial dysfunction–including oxidative stress, impaired calcium signaling, mitophagy deficits, disrupted proteostasis, and electron transport chain abnormalities, as central to AD pathogenesis. These dysfunctions contribute to synaptic degeneration, increased reactive oxygen species, and neuronal death. This review consolidates current knowledge on the mechanistic pathways of mitochondrial impairment in AD and their downstream effects on neuronal health. We also explore the therapeutic potential of multitarget approaches, including agents targeting Aβ and tau pathology, oxidative stress mitigation, mitochondrial quality control, and synaptic restoration. By integrating evidence from recent preclinical and clinical studies, this work highlights mitochondrial homeostasis as a promising frontier for disease-modifying therapies in AD.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fnsyn.2025.1724377</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fnsyn.2025.1724377</link>
        <title><![CDATA[Synaptic transmission in supragranular layers of the human cortex – comparative review of structure, function, and plasticity]]></title>
        <pubdate>2025-12-10T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Amelie Eichler</author><author>Pia Kruse</author><author>Charlotte Schob</author><author>Maximilian Lenz</author>
        <description><![CDATA[Synapses are the highly specialized connection sites between neurons enabling the establishment of complex neuronal networks. As highly plastic structures, synapses collocate both the transmission and storage of information, which is an essential prerequisite for learning and memory. Since synaptic deficits are associated with degenerative and neuropsychiatric diseases, it is essential to understand the mechanisms of synaptic plasticity. Throughout evolution, the human brain has developed distinct characteristics, such as supragranular expansion and enhanced long-range connectivity, suggesting an evolutionary specialization of synapses. Recent collaborative research, employing slice preparations obtained from neurosurgical resections of the human neocortex, has significantly advanced our understanding of the unique structural and functional properties of the human neocortex. This review investigates findings derived from diverse experimental methodologies, highlighting specific synaptic features. Focusing on synapses in supragranular layers, we discuss the distinctive synaptic structure, function, and mechanisms of plasticity that contribute to the unique circuitry of the adult human brain. Additionally, we outline emerging directions of research aimed at further elucidating the functionality of human cortical networks.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fnsyn.2025.1732955</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fnsyn.2025.1732955</link>
        <title><![CDATA[From microelectrode arrays to all-optical and multimodal neural interfaces: emerging platforms for spatiotemporal interrogation of in vitro neural circuits]]></title>
        <pubdate>2025-12-09T00:00:00Z</pubdate>
        <category>Mini Review</category>
        <author>Song Wang</author><author>Sarah Gordon</author><author>Chris French</author><author>Ranjith R. Unnithan</author><author>Dechuan Sun</author>
        <description><![CDATA[Understanding how synaptic interactions lead to circuit dynamics for neural computation requires experimental tools that can both observe and perturb neuronal activity across spatial and temporal scales. Microelectrode arrays (MEAs) provide scalable access to population spiking activity, yet they lack the spatial resolution and molecular specificity to precisely dissect synaptic mechanisms. In contrast, recent advances in optogenetic actuators, genetically encoded calcium and voltage indicators, and patterned photostimulation have transformed in vitro research, enabling all-optical interrogation of synaptic plasticity, functional connectivity, and emergent network dynamics. Further progress in transparent MEAs and hybrid optical–electrical systems has bridged the divide between electrophysiology and optical control, allowing simultaneous, bidirectional interaction with biological neural networks (BNNs) and real-time feedback modulation of activity patterns. Together, these multimodal in vitro platforms provide unprecedented experimental access to how local interactions shape global network behavior. Beyond technical integration, they establish a foundation for studying biological computation, linking mechanistic understanding of synaptic processes with their computational outcomes. This mini-review summarizes the progression from conventional MEA-based electrophysiology, through all-optical interrogation, to integrated multimodal frameworks that unite the strengths of both modalities.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fnsyn.2025.1656759</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fnsyn.2025.1656759</link>
        <title><![CDATA[GABAB receptors negatively modulate excitatory plasticity at the mossy fiber synapse onto parvalbumin-expressing basket and axo-axonic cells in the dentate gyrus]]></title>
        <pubdate>2025-11-18T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Rita M. Loureiro</author><author>Sam A. Booker</author><author>Akos Kulik</author><author>Imre Vida</author>
        <description><![CDATA[IntroductionGABAB receptors (GABABRs) are important modulators of neuronal excitability, synaptic transmission and plasticity in principal cells (PCs). While at the cellular level they can inhibit synaptic transmission directly, at the network level, due to a net disinhibitory effect, they promote plasticity in PCs. However, their effect on plasticity in GABAergic interneurons (INs) is less well-understood.MethodsIn this study, we have combined quantitative immunoelectron microscopy and ex vivo whole-cell recordings to investigate the surface expression of GABABRs and their modulation of synaptic plasticity at mossy fiber (MF) inputs onto parvalbumin-expressing interneurons (PV-INs) in the rat dentate gyrus (DG).ResultsImmunoelectron microscopy confirmed the expression of the GABABRs and their effector channel Kir3.1 on PV-IN dendritic shafts. Theta-burst extracellular stimulation of MFs resulted in robust long-term potentiation (LTP) in basket cells (BCs) and axo-axonic cells (AACs), the two main types of DG PV-INs. LTP in both types was strongly reduced, but not abolished, by the GABABR agonist baclofen.Discussion/ConclusionFinally, pre-application of SCH-23390, a blocker of Kir3 channels, occluded the inhibitory effect of baclofen on LTP. These results demonstrate that postsynaptic GABABRs negatively regulate synaptic plasticity at MF synapses onto DG perisomatic-inhibitory PV-INs via Kir3 channels.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fnsyn.2025.1701349</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fnsyn.2025.1701349</link>
        <title><![CDATA[Opposite serotonergic modulation of sharp waves in the dorsal and ventral hippocampus]]></title>
        <pubdate>2025-11-05T00:00:00Z</pubdate>
        <category>Brief Research Report</category>
        <author>Charalampos L. Kandilakis</author><author>Costas Papatheodoropoulos</author>
        <description><![CDATA[Serotonin plays a crucial role in regulating hippocampal network dynamics, however, its effects on sharp wave–ripples (SPWs), a pattern fundamental for memory consolidation and emotional processing, remain incompletely understood, particularly along the dorsoventral axis. Using hippocampal slices from adult rats, we compared serotonergic modulation of SPWs and associated multiunit activity (MUA) in dorsal and ventral CA1 regions. Serotonin (1–100 μM) was applied to evaluate dose dependent and region-specific effects on SPW amplitude, duration, frequency, and neuronal firing. We found that serotonin reduces SPW amplitude in both hippocampal segments, decreases the rate of SPW occurrence in the dorsal hippocampus, and increases the rate of SPW occurrence in the ventral hippocampus, but only at relatively low concentrations. The suppressive effect on SPW amplitude is accompanied by a reduction in firing frequency during SPWs in both regions, whereas the enhancing effect of low serotonin concentrations on SPW rate in the ventral hippocampus is associated with an excitatory action on basal neuronal activity. These results reveal a region-specific, and dose-dependent serotonergic modulation of SPWs, reflecting distinct excitatory/inhibitory balances and receptor subtype distributions along the hippocampal axis. Functionally, serotonergic suppression of dorsal SPWs may regulate cognitive processes, whereas bidirectional modulation in the ventral hippocampus may fine-tune affective and stress-related responses. Our findings highlight dorsoventral specialization of serotonergic control over hippocampal network patterns, providing insights into the mechanisms of dorsoventral hippocampal specialization and the symptom heterogeneity of neuropsychiatric disorders involving serotonergic dysfunction.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fnsyn.2025.1656232</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fnsyn.2025.1656232</link>
        <title><![CDATA[Is it possible to prevent excessive synaptic pruning in schizophrenia? Possibilities and limitations]]></title>
        <pubdate>2025-10-15T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Agnieszka Pawlak</author><author>Jakub Stefanowicz</author><author>Zofia Kotkowska</author><author>Agata Gabryelska</author><author>Marcin Sochal</author><author>Filip Napieraj</author><author>Magdalena Kotlicka-Antczak</author><author>Dominik Strzelecki</author>
        <description><![CDATA[BackgroundSynaptic pruning is a critical neurodevelopmental process that eliminates redundant or weak synaptic connections to optimize brain circuitry. In schizophrenia, converging evidence from imaging, genetic, and postmortem studies suggests that this process is pathologically accelerated, particularly in the prefrontal cortex during adolescence. The resulting reduction in synaptic density has been implicated in disrupted neural connectivity observed in psychosis, with the onset of cognitive impairment and negative symptoms.ObjectiveThis review explores whether modulating aberrant synaptic pruning could serve as a preventive or early intervention strategy for schizophrenia. We analyze domains with emerging therapeutic relevance: tetracycline antibiotics, the complement system and C4 gene, kynurenine pathway modulation, epigenetic therapies, neuroprotective strategies (e.g., BDNF, NF-κB, progranulin), genetic and transcriptional regulators of pruning, and other new, mostly hypothetical, options. We also discuss the limitations of the impact on pruning.MethodsWe conducted a structured review of the mechanisms involved in pruning, as well as clinical trials, preclinical studies, and mechanistic models that investigate molecular targets influencing synaptic pruning in schizophrenia.ResultsSeveral molecular pathways have been implicated in abnormal synaptic pruning in schizophrenia, including complement C4A overexpression, kynurenine pathway imbalance (KYNA/QUIN), and dysregulation of microglial and transcriptional modulators such as MEF2C and TCF4. While retrospective studies suggest minocycline or doxycycline may reduce psychosis risk, randomized trials remain inconclusive. Emerging interventions, including LSD1 inhibitors, BDNF/progranulin enhancers, and lifestyle-based epigenetic modulation, show promise but require further validation in clinical settings. We also discuss the limitations of these methods, including safety considerations.ConclusionTargeted modulation of synaptic pruning represents a promising but complex therapeutic strategy. The timing, specificity, and reversibility of interventions are crucial to avoid disrupting essential neurodevelopment. Future efforts should focus on identifying biomarkers for patient stratification and validating preventive strategies in high-risk populations.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fnsyn.2025.1661342</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fnsyn.2025.1661342</link>
        <title><![CDATA[AMPA receptors in the evolving synapse: structure, function, and disease implications]]></title>
        <pubdate>2025-10-10T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Fleming Francis</author><author>Dewan Chettri</author><author>Deepak Nair</author>
        <description><![CDATA[Synapses, once considered static conduits for neuronal signals, are now recognized as dynamic, multifunctional structures critical to brain function, plasticity, and disease. This evolving understanding has highlighted the tripartite nature of synapses, including pre-synaptic terminals, post-synaptic compartments, and regulatory glial elements. Among excitatory synapses, glutamatergic transmission dominates, with AMPA receptors (AMPARs) playing a central role in fast synaptic signaling. AMPARs are tetrameric, ligand-gated ion channels that mediate rapid depolarization and are tightly regulated by subunit composition, trafficking, and interactions with scaffolding and signaling proteins. Their activity-dependent modulation underpins key processes such as long-term potentiation and depression, central to learning and memory. Importantly, dysfunctions in AMPAR expression, localization, or signaling are increasingly linked to neurological and psychiatric disorders including autism spectrum disorders, epilepsy, schizophrenia, and Alzheimer's disease. This review discusses AMPAR biology in the context of synaptic organization, highlighting recent advances and ongoing challenges in understanding their roles in health and disease.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fnsyn.2025.1672646</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fnsyn.2025.1672646</link>
        <title><![CDATA[Exploring the singularity of human neurons: keep calm and carry on]]></title>
        <pubdate>2025-10-02T00:00:00Z</pubdate>
        <category>Mini Review</category>
        <author>Baptiste Libé-Philippot</author>
        <description><![CDATA[The human brain’s increased cognitive abilities are underpinned by evolutionary adaptations at the molecular, cellular, and circuit levels of neural structures. This perspective explores how protracted neuronal development and divergent cell intrinsic neuronal properties, including neuronal excitability, contribute to human neurobiological singularity. Those cellular aspects rely on molecular evolutionary innovations, including evolution of gene regulation and gene duplications that play critical roles in prolonging synaptogenesis and reducing neuronal excitability. These molecular evolutionary innovations are shown to interact with core neurodevelopmental molecular pathways linked to neurodevelopmental disorders. Furthermore, complementary multimodal and multiscale approaches offer promising platforms to study these processes and develop species-relevant therapeutic strategies. They include ex vivo acute brain slices and organotypic cultures which offer emerging tools for understanding human species-specificities and neural disorders.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fnsyn.2025.1638371</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fnsyn.2025.1638371</link>
        <title><![CDATA[PKMζ drives spatial memory reconsolidation but not maintenance]]></title>
        <pubdate>2025-08-13T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>João Rodrigo de Oliveira</author><author>Janine I. Rossato</author><author>Johseph P. G. Souza</author><author>Rodrigo Orvate</author><author>Livia Carneiro</author><author>Ana Luizi Baracho</author><author>Martín Cammarota</author>
        <description><![CDATA[Non-reinforced reactivation destabilizes spatial memory in the Morris water maze (MWM), triggering reconsolidation, a protein synthesis-dependent process that restabilizes reactivated memories. PKMζ is a constitutively active, atypical PKC isoform implicated in memory storage. However, the potential involvement of this kinase in spatial memory reconsolidation remains unexplored. We found that intra-dorsal CA1 infusion of the PKMζ inhibitor myristoylated ζ-inhibitory peptide (ZIP), but not its inactive scrambled analog scZIP, following non-reinforced spatial memory reactivation in the MWM, induced time-dependent, long-lasting amnesia in adult male Wistar rats. This effect was replicated by silencing PKMζ mRNA translation with phosphorothioated antisense oligonucleotides, but not by inhibiting the related PKCι/λ with ICAP, and was prevented by disrupting hippocampal GluN2B-NMDAR signaling with RO25-6981, proteasome activity with clasto-lactacystin β-lactone, and AMPAR endocytosis with dynasore hydrate. ZIP had no effect on retention when given without reactivation or after reinforced reactivation. These findings suggest hippocampal PKMζ is necessary for spatial memory reconsolidation in the MWM, but not for its passive maintenance.]]></description>
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