Retinotopy is a fundamental organizational principle of the visual system, where neighboring neurons represent adjacent points in visual space. This spatial relationship is established by precise anatomical wiring across successive areas, e.g., from the retina to the lateral geniculate nucleus (LGN) to the visual cortex. To examine the precision of this topographic arrangement within the long-range projection axons themselves, we recorded retinal ganglion cell (RGC) axons in the mouse optic tract (OT) and mapped their receptive fields (RFs). As expected for a retinotopically organized area, we found that nearby LGN cell pairs had significantly smaller RF distances than distant pairs. In contrast, no such relationship was observed among RGC axons in the OT. Modelling analyses further confirmed that the observed RF distances in the OT were incompatible with any locally retinotopic arrangement. Instead, the OT retained only coarse topography, with ~18° RF deviations or ~40 μm axonal displacements from an ideal retinotopic organization. These results demonstrate that the mouse OT lacks fine-scale retinotopy and maintains only broad topographic structure.

Brain pericytes play essential roles in vascular homeostasis, including capillary stabilization and maintenance of the blood–brain barrier. Lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria, is known to trigger inflammatory responses not only systemically but also within the central nervous system. In this study, we investigated the effects of LPS on the phenotype and transcriptome of brain vascular pericytes. LPS promoted bromodeoxyuridine incorporation in the primary culture of human brain pericytes as well as increased the number of Ki67-positive cells, indicating enhanced pericyte proliferation. Morphological analysis revealed that LPS decreased the cellular aspect ratio, suggesting altered cellular elongation. Transcriptomic profiling showed that LPS-induced differentially expressed genes were enriched for terms related to cell proliferation, angiogenesis, and blood–brain barrier function. Because pericytes critically regulate neurovascular coupling and metabolic support for active neurons, these LPS-induced alterations may ultimately perturb the microvascular control of neural circuits. These results suggest that LPS has the potential to regulate brain vascular function by inducing morphological and functional changes in pericytes.

The regulatory mechanisms of postnatal neurogenesis in the subventricular zone (SVZ) and the rostral migratory stream (RMS) are still not fully understood. Recent evidence suggests that neurogenesis in the SVZ/RMS may be regulated by neurons located directly in these regions. To date, two populations of neurons residing in the SVZ/RMS, which display the morphological characteristics of mature neurons, have been identified: nitric oxide (NO)-producing neurons and neurons expressing secretagogin (SCGN). The aim of our study was to map the possible projections of these neuronal populations in the SVZ/RMS. All experiments were performed on adult male Wistar albino rats. To test the hypothesis that nNOS- and SCGN-positive neurons of the SVZ and RMS send their axons to the striatum, we injected this target brain structure with the retrograde fluorescent tracer Fluoro-Gold (F-G). To verify the identity of nitrergic neurons and SCGN- expressing neurons, double immunofluorescent labeling with anti-nNOS/anti-SCGN and anti-F-G was performed. Microscopic analysis revealed the presence of F-G, administered into the striatum, in cells of the SVZ and different parts of the RMS. F-G-labeled cells in the SVZ/RMS were identified as either nitrergic neurons or SCGN-expressing neurons. Our results demonstrate a connection between mature neurons of the SVZ/RMS and the striatum.

How can we make sense of large-scale recordings of neural activity across learning? Theories of neural network learning with their origins in statistical physics offer a potential answer: for a given task, there are often a small set of summary statistics that are sufficient to predict performance as the network learns. Here, we review recent advances in how summary statistics can be used to build theoretical understanding of neural network learning. We then argue for how this perspective can inform the analysis of neural data, enabling better understanding of learning in biological and artificial neural networks.

Dissociated neuronal cultures provide a powerful, simplified model for investigating self-organized prediction and information processing in neural networks. This review synthesizes and critically examines research demonstrating their fundamental computational abilities, including predictive coding, adaptive learning, goal-directed behavior, and deviance detection. A unique contribution of this work is the integration of findings on network self-organization, such as the development of critical dynamics optimized for information processing, with emergent predictive capabilities, the mechanisms of learning and memory, and the relevance of the free energy principle within these systems. Building on this, we discuss how insights from these cultures inform the design of neuromorphic and reservoir computing architectures, aiming to enhance energy efficiency and adaptive functionality in artificial intelligence. Finally, this review outlines promising future directions, including advancements in three-dimensional cultures, multi-compartment models, and brain organoids, to deepen our understanding of hierarchical predictive processes in both biological and artificial systems, thereby paving the way for novel, biologically inspired computing solutions.

Neurodegenerative disorders affect millions of people worldwide, presenting not only motor impairments but also severe mood and cognitive disturbances. Current treatments remain largely symptomatic and non-specific, sometimes even exacerbating psychiatric complications. Emerging evidence indicates that maladaptive plasticity in neural circuits could be responsible for both motor and non-motor symptoms. This Research Topic, "Circuits Plasticity in Neurodegenerative Disorders: Targeting Mood Disorders," gathers studies employing neuroimaging, chemogenetics, and molecular techniques, along with opinion reviews to elucidate the shared neurobiological mechanisms linking psychiatric symptoms and neurodegeneration.In this issue, (Wilt et al., 2025) focused on the zona incerta (ZI), a small, understudied subthalamic structure now recognized as a heterogeneous hub. Initially investigated for its role in ingestive behaviors and basic survival, numerous investigations have then established the ZI's contributions in motor control, particularly in Parkinson's disease (PD), with deep brain stimulation improving motor symptoms when applied not only to subthalamic nucleus but also to ZI. Wilt et al. synthesize recent findings highlighting the contribution of ZI to reward motivation and hypothesizing its potential involvement in addiction. These evidences include the ZI's connectivity, or its neuronal populations reminiscent of the substantia nigra pars compacta (SNc) and ventral tegmental area composition, with the notable presence of dopaminergic neurons. Thus, the ZI may be integrated into neural circuits underlying aberrant reward processes, including addiction, although its precise role in encoding reward prediction errors or driving compulsive behaviors for instance remains unclear. The authors suggest that targeting ZI circuits could open novel therapeutic avenues for treating addiction-related disorders.Expanding on connectivity, (Cirillo et al., 2025) revealed a direct anatomical pathway between the SNc and the thalamus in young healthy humans. Using multi-shell high-angular resolution diffusion imaging (MS-HARDI) tractography on 10 subjects (5 males, 5 females; ages 25-30), they precisely segmented the SNc and thalamus from high-resolution 3D T1 images. Their probabilistic tractography isolated streamlines traversing the SNc and terminating in the thalamus, while excluding fibers to other regions. Approximately 12% of SNc streamlines are directly connected with the thalamus in both hemispheres, a finding further supported by normative PET analysis of dopamine receptor densities showing similar profiles in both regions. Despite limitations such as imaging resolution and potential false positives, reproducibility across two MS-HARDI schemes reinforces this nigro-thalamic pathway, expanding our understanding of dopaminergic regulation beyond the classic nigro-striatal circuit.In a neuromodulation study, (Lipari et al., 2024) investigated whether selectively inhibiting serotonin (5-HT) projections from the dorsal raphe nucleus could improve L-DOPA-induced dyskinesia (LID) and Parkinson's disease-associated psychosis (PDAP) in a rat model of PD. Using TPH2-Cre Long Evans rats with bilateral 6-hydroxydopamine lesions of the medial forebrain bundle, they infused a Cre-dependent inhibitory DREADD into the dorsal raphe and administered the designer drug Compound 21 (C21) during chronic L-DOPA treatment. Motor performance was measured via a stepping test, and abnormal involuntary movements (AIMs) were quantified, with prepulse inhibition (PPI) assessing sensorimotor gating. Acute inhibition of dorsal raphe 5-HT neurons with C21 significantly reduced LID without affecting sensorimotor function, suggesting that abnormal 5-HT activity contributes to dyskinetic movements.Addressing molecular mechanisms of depressive behavior, (He et al., 2024) explored how modulation of L-type Ca²⁺ channel activity and DNA methylation interact in an lipopolysaccharide (LPS)-induced depression model in male C57BL/6J mice. Chronic LPS injections reduced body weight, sucrose preference, and increased immobility in the forced swim test, accompanied by decreased Dnmt3a expression in the hippocampal dentate gyrus. While the antidepressant Venlafaxine reversed these deficits and normalized inflammation markers (GFAP), the L-type Ca²⁺ channel agonist BAY K 8644 alone only partially improved depressive-like behavior without restoring Dnmt3a levels. Notably, combining BAY K 8644 with L-methionine significantly enhanced behavioral improvements, suggesting a synergistic interaction between Ca²⁺ channel modulation and DNA methylation in regulating neurodegenerative-induced mood disorders.Finally, (Dong et al., 2021) review the connectivity and functionality of the external segment of the globus pallidus (GPe), once considered a simple relay in the BG but now considered as a heterogeneous structure. The GPe comprises predominantly GABAergic neurons, divided into prototypic and arkypallidal subtypes, and a minority of cholinergic cells. The review details extensive afferents from the striatum, subthalamic nucleus, cortex, thalamus, and brainstem, and diverse efferents to BG output nuclei and the cortex. In PD, dopaminergic loss disrupts GPe firing patterns and increases β oscillations, contributing to both motor and non-motor symptoms. The authors emphasize the need to investigate distinct GPe neurons subpopulation to improve diagnosis and therapeutic interventions for PD.All together, these articles underscore the evolution of our comprehension of neurodegenerative disorders, driven by maladaptive circuit plasticity across diverse neural networks. By integrating advanced techniques, the research highlights novel circuit-based therapeutic targets that may pave the way for more precise and effective treatments for mood disorders.YMV initiated the Research Topic. RM and PH co-hosted this research topic. RM and YMV wrote the draft of this editorial, with help from PH.

[This corrects the article DOI: 10.3389/fncir.2024.1463941.].

Experience-dependent neural plasticity enables the brain to adapt to diverse and dynamic environments by reshaping circuits. In the adult visual system, this plasticity can be elicited by repeated sensory stimuli; however, its temporal dynamics and underlying mechanisms remain unclear. Here, we investigated the regulation of visual response potentiation induced by repeated light flashes in the primary visual cortex of awake adult mice. Our findings revealed two distinct temporal phases of potentiation: a rapid phase occurring within seconds and a cumulative phase developing over hours to days. Notably, the identification of this rapid phase phenomenon adds to and refines the prevailing view that visual plasticity in the adult cortex is predominantly slow. Additionally, exposure to visual stimuli enhanced spontaneous slow-wave activity in the visual cortex during non-REM sleep. This plasticity was significantly impaired in Grin2a (NR2A) knockout mice, a model of schizophrenia, which mirrors visual plasticity deficits observed in human patients. The dual temporal characteristics of flash-evoked visual plasticity likely reflect multifaceted aspects of adult brain functionality, encompassing processes related to memory, learning, and neurological disorders. This model of visual plasticity in defined neural circuits provides a simplified yet robust and extensible framework for exploring the neural mechanisms underlying adaptive and maladaptive behavioral changes.

According to the World Health Organization, the number of people suffering from depressive disorders worldwide is approaching 350 million. The consequences of depressive disorders include considerable worsening of the quality of life, which frequently leads to social isolation. One of the key factors which may cause depression in adulthood is early life stress, in particular, insufficient maternal care during infancy. Studies performed with children raised in orphanages have shown that long-term complete absence of maternal care (chronic early life stress) leads to vulnerability to emotional disorders, including depression, in adulthood. All of the above dictates the need for a deep understanding of the mechanisms of the pathogenicity of stress in neurogenesis. Therefore, the consequences of stress experienced in the early stages of development are actively studied in animal models. A large body of evidence has accumulated indicating stress-induced changes in gene expression and behavioral disorders in adulthood. However, the connection between the molecular biology of neurons and complex behavior runs through the synaptic connections linking these neurons into complex neural networks. In turn, coordinated activity in neuronal ensembles, achieved by a balance of synaptic excitation and inhibition, is the basis of complex behavior. Unfortunately, the effect of stress on synaptic interactions of neurons remains poorly understood.