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How to Rewire the Brain—Neuroplasticity

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A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Molecular and Cellular Neuroscience".

Deadline for manuscript submissions: 19 June 2026 | Viewed by 29172

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Dr. Jianyang Du

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Guest Editor

Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, TN 38163, USA
Interests: neural circuit; mouse behavior; psychiatric disorders; synaptic transmission and plasticity; learning and memory
Special Issues, Collections and Topics in MDPI journals

Dr. Hui Lu

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Guest Editor

Department of Pharmacology and Physiology, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA
Interests: machine learning; neural circuit coding of behavior; neural ensemble activity; neurological disorders; system neuroscience
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We would like to welcome you to this Special Issue of our scientific journal, dedicated to exploring the intricate world of brain circuits and neuroplasticity. Neuroplasticity, the brain's remarkable ability to reorganize itself in response to experiences, learning, and injury, is a cornerstone of neuroscience research. This Special Issue, titled “How to Rewire the Brain—Neuroplasticity”, explores the dynamic processes underpinning neural adaptation and their profound implications for cognition, behavior, and recovery from neurological disorders.

Through cutting-edge studies, we delve into the molecular, cellular, and systemic mechanisms that drive plasticity, from synaptic remodeling to large-scale network reorganization. Our contributors investigate how factors such as age, environment, and genetics influence plasticity and how these insights inform innovative therapeutic strategies, including neurorehabilitation, brain stimulation, and pharmacological interventions.

By unraveling the complexities of neuroplasticity, this Special Issue seeks to bridge foundational science with translational applications, offering new perspectives on how we can harness the brain’s adaptability to optimize health and function. We invite readers to explore these advances and their transformative potential.

Dr. Jianyang Du
Dr. Hui Lu
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Brain Sciences is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

brain circuits
neural networks
synaptic plasticity
neural development
network dynamics
neural coding
information processing
neuron–glia interaction
behavioral output
neurological disorders

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Published Papers (5 papers)

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Research

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30 pages, 6603 KB

Open AccessArticle

Reduced Cortical Pyramidal Neuron Membrane Excitability and Synaptic Function in Parkinsonian Mice and Their Restoration by L-Dopa Treatment: Indirect Mediation by Striatal Dopaminergic Activity

by Huimin Chen, Manli Zhong, Geng Lin, Francesca-Fang Liao and Fu-Ming Zhou

Brain Sci. 2026, 16(3), 285; https://doi.org/10.3390/brainsci16030285 - 3 Mar 2026

Viewed by 742

Abstract

Background: We previously established that striatal, but not cortical, dopaminergic activation stimulates movement, indicating that the crucial and original site of dopaminergic stimulation of motor function is the striatum, not the motor cortex. In the present study, we have further investigated the potential effects of the cortical and striatal dopaminergic activity on cortical pyramidal neuron physiology. Methods and Results: First, under a constant fluorescence imaging condition, we established that DA innervation and D1R and D2R expression were very low in the cerebral cortex but very high in the striatum. Second, we performed cellular neurophysiological experiments on layer 2/3 pyramidal neurons in the primary motor cortex (M1) in tyrosine hydroxylase gene knockout (TH-KO) DA-depleted mice that have hyperfunctional DA receptors. Using brain slice–whole-cell patch-clamping techniques, we found that M1 layer 2/3 pyramidal neurons had lower input resistance, stronger inward rectification, more negative RMP, and fired fewer spikes in DA-depleted TH-KO mice than in DA-intact WT mice; M1 layer 2/3 pyramidal neurons also had a diminished synaptic release function with reduced frequencies for spontaneous and miniature excitatory synaptic currents in TH-KO mice compared to WT mice. Third, we also found that when TH-KO mice were treated with L-dopa before brain slice preparation, these neurophysiological deficits of M1 layer 2/3 pyramidal neurons were reversed, but 30 min incubation of cortical brain slices with 10–20 μM DA produced no detectable effect in M1 layer 2/3 pyramidal neurons in TH-KO mice and WT mice. Fourth, Golgi staining showed that cortical pyramidal neuron morphology was indistinguishable between WT mice and TH-KO mice. Conclusions: Our results indicate that DA loss in the striatum, not in the cortex, indirectly reduces cortical pyramidal neuron membrane excitability and weakens synaptic function. Our data also indicate that (1) the normal direct effects of the cortical DA system on cortical pyramidal neurons are weak, (2) the striatal DA system is the dominant DA system in the brain, and (3) striatal DA activity can indirectly increase cortical neuron activity (spike firing and synaptic activity) and thus critically contribute to brain function. Additionally, our data suggest that in DA depletion rodent PD models, DA loss-induced effects on cortical pyramidal neurons and other neurons are functional rather than structural, such that DA replenishment restores motor function almost instantaneously. These findings provide important insights into how the brain’s dopaminergic system controls our motor and cognitive functions and indicate that the striatum is the main therapeutic target of dopaminergic drugs. Full article

(This article belongs to the Special Issue How to Rewire the Brain—Neuroplasticity)

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29 pages, 8282 KB

Open AccessArticle

Dopaminergic Inhibition of the Inwardly Rectifying Potassium Current in Direct Pathway Medium Spiny Neurons in Normal and Parkinsonian Striatum

by Qian Wang, Yuhan Wang, Francesca-Fang Liao and Fu-Ming Zhou

Brain Sci. 2025, 15(9), 979; https://doi.org/10.3390/brainsci15090979 - 12 Sep 2025

Cited by 1 | Viewed by 2007

Abstract

Background: Despite the profound behavioral effects of the striatal dopamine (DA) activity and the inwardly rectifying potassium channel (Kir) being a key determinant of striatal medium spiny neuron (MSN) activity that strongly affects behavior, previously reported DA regulations of Kir are conflicting and incompatible with MSN function in behavior. Methods and Results: Here, we used DA depletion mouse models that have hyperfunctional DA receptors such that potential DA regulation of Kir may be enhanced and relatively large and thus detected reliably. We show that in striatal brain slices from normal mice with an intact striatal DA system, the predominant effect of DA activation of D1Rs in D1-MSNs is to cause a modest depolarization and an increase in input resistance by inhibiting Kir, thus moderately increasing the spike outputs from behavior-promoting D1-MSNs. In brain slices from parkinsonian (DA-depleted) striatum, DA increases D1-MSN intrinsic excitability more strongly than in normal striatum, consequently more strongly increasing D1-MSN spike firing that is behavior-promoting. This DA inhibition of Kir is occluded by the Kir blocker barium chloride (BaCl₂). In behaving parkinsonian mice, BaCl₂ microinjection into the dorsal striatum stimulates movement and also occludes the motor stimulation of D1R agonism. Conclusions: Taken together, our results resolve the long-standing question about what D1R agonism does to D1-MSN excitability in normal and parkinsonian striatum and strongly indicate that D1R inhibition of Kir is a key ion channel mechanism that mediates the profound motoric and behavioral stimulation of striatal D1R activation in normal and parkinsonian animals. Full article

(This article belongs to the Special Issue How to Rewire the Brain—Neuroplasticity)

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17 pages, 2085 KB

Open AccessArticle

Chronic Fluoxetine Treatment Desensitizes Serotoninergic Inhibition of GABAergic Inputs and Intrinsic Excitability of Dorsal Raphe Serotonin Neurons

by Wei Zhang, Ying Jin and Fu-Ming Zhou

Brain Sci. 2025, 15(4), 384; https://doi.org/10.3390/brainsci15040384 - 8 Apr 2025

Cited by 2 | Viewed by 2551

Abstract

Background: Dorsal raphe serotonin (5-hydroxytryptamine, 5-HT) neurons are spontaneously active and release 5-HT that is critical for normal brain function and regulates mood and emotion. Serotonin reuptake inhibitors (SSRIs) increase the synaptic and extracellular 5-HT level and are effective in treating depression. Treatment of two weeks or longer is often required for SSRIs to produce clinical benefits. The cellular mechanism underlying this delay is not fully understood. Methods and Results: Using whole-cell patch clamp recording in brain slices, here we show that the GABAergic inputs inhibit the spike firing of raphe 5-HT neurons. This GABAergic regulation was reduced by 5-HT; additionally, this 5-HT effect was prevented by the G-protein-activated inwardly rectifying potassium (GirK) channel inhibitor tertiapin-Q, indicating a contribution of 5-HT activation of GirK channels in GABAergic presynaptic axon terminals. Equally important, after 14 days of treatment with fluoxetine, a widely used SSRI type antidepressant, the 5-HT inhibition of GABAergic inputs was downregulated. Furthermore, chronic fluoxetine treatment downregulated the 5-HT activation of the inhibitory GirK current in 5-HT neurons. Conclusions: Taken together, our results suggest that chronic fluoxetine treatment, by blocking 5-HT reuptake and hence increasing the extracellular 5-HT level, can downregulate the function of 5-HT1B receptors on the GABAergic afferent axon terminals synapsing onto 5-HT neurons, allowing extrinsic GABAergic neurons to more effectively influence 5-HT neurons; simultaneously, chronic fluoxetine treatment also downregulated somatic 5-HT autoreceptor-activated GirK channel-mediated hyperpolarization and decrease in input resistance, rendering 5-HT neurons resistant to autoinhibition and leading to increased 5-HT neuron activity. These neuroplastic changes in raphe 5-HT neurons and their GABAergic afferents may contribute to the behavioral effect of SSRIs. Full article

(This article belongs to the Special Issue How to Rewire the Brain—Neuroplasticity)

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11 pages, 2142 KB

Open AccessArticle

Dance Training and the Neuroplasticity of the Vestibular-Ocular Reflex: Preliminary Findings

by Raghav H. Jha, Erin G. Piker, Miranda Scalzo and Diana Trinidad

Brain Sci. 2025, 15(4), 355; https://doi.org/10.3390/brainsci15040355 - 29 Mar 2025

Viewed by 2318

Abstract

Background: The impact of dance training on brainstem-mediated vestibular reflexes remains unclear. This study examined the vestibulo-ocular reflex (VOR) and its suppression during high-speed head movements, which may closely resemble the head-turning speeds used in dancers’ spotting techniques, using the video head impulse test. Methods: Eighteen female college students (mean age: 21 years) were divided into two groups—nine trained dancers (≥six years of dance training) and nine age-matched non-dancers—all without a history of hearing, vestibular, or neurological disorders. VOR function was assessed using the head impulse paradigm (HIMP) and the suppression head impulse paradigm (SHIMP) for right and left lateral stimulation, with minimum head velocities of 150°/s. Results: All participants exhibited VOR measures within normal limits and the VOR gain of dancers did not significantly differ from that of non-dancers. However, most dancers reported a preference for right-sided pirouettes and the right-side SHIMP gain negatively correlated with years of training, suggesting a link between preferred turning direction and VOR suppression ability. Furthermore, dancers with over 15 years of training exhibited earlier anti-compensatory saccade latencies (~75 ms) during SHIMP. Conclusions: Trained dancers maintain a healthy VOR and may develop enhanced voluntary control, enabling more effective VOR suppression. The earlier onset of anti-compensatory saccades suggests neural adaptations in eye–head coordination for high-velocity movements. Given the study’s small sample size and the inclusion of non-fulltime dancers, future research with larger samples of professional dancers is needed for enhanced generalizability. These findings provide preliminary evidence of dance-related neuroplasticity in brainstem-mediated vestibular reflexes and open new research avenues. Full article

(This article belongs to the Special Issue How to Rewire the Brain—Neuroplasticity)

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21 pages, 1040 KB

Open AccessEditor’s ChoiceReview

Neuroplasticity and Nervous System Recovery: Cellular Mechanisms, Therapeutic Advances, and Future Prospects

by Ligia Gabriela Tataranu and Radu Eugen Rizea

Brain Sci. 2025, 15(4), 400; https://doi.org/10.3390/brainsci15040400 - 15 Apr 2025

Cited by 17 | Viewed by 20287

Abstract

Neuroplasticity, the ability of the nervous system to adapt structurally and functionally in response to environmental interactions and injuries, is a cornerstone of recovery in the central (CNS) and peripheral nervous systems (PNS). This review explores the mechanisms underlying neuroplasticity, focusing on the dynamic roles of cellular and molecular processes in recovery from nervous system injuries. Key cellular players, including Schwann cells, oligodendrocytes, and neural stem cells, are highlighted for their contributions to nerve repair, myelination, and regeneration. Advances in therapeutic interventions, such as electrical stimulation, bioluminescent optogenetics, and innovative nerve grafting techniques, are discussed alongside their potential to enhance recovery and functional outcomes. The molecular underpinnings of plasticity, involving synaptic remodeling, homeostatic mechanisms, and activity-dependent regulation of gene expression, are elucidated to illustrate their role in learning, memory, and injury repair. Integrating emerging technologies and therapeutic approaches with a foundational understanding of neuroplasticity offers a pathway toward more effective strategies for restoring nervous system functionality after injury. Full article

(This article belongs to the Special Issue How to Rewire the Brain—Neuroplasticity)

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