Regulation of Chloride Gradients and Neural Plasticity

2019 ◽  
Author(s):  
Jimena Perez-Sanchez ◽  
Yves De Koninck
Keyword(s):  
Synaptic Plasticity ◽  
Neural Plasticity ◽  
Neuronal Excitability ◽  
Dynamic Effect ◽  
Synaptic Inhibition ◽  
Gamma Aminobutyric Acid ◽  
Chloride Homeostasis ◽  
System P ◽  
Dual Action ◽  
The Central Nervous System

One of the most remarkable properties of neural circuits is the ability to restructure their synaptic connections throughout life. This synaptic plasticity allows neurons to structurally reorganize and adapt their function in response to experience. Among the multiple mechanisms that can modulate this property is synaptic inhibition by gamma-Aminobutyric acid (GABA) and/or glycine ionotropic receptors, which allow the flow of chloride and bicarbonate ions through the membrane. Neurons rely upon tight regulation of intracellular chloride for efficient inhibition through these receptors. The maintenance of chloride gradients is important not only to determine the strength of synaptic inhibition but also to determine its nature. Indeed, this inhibition can be hyperpolarizing or depolarizing, or with no outright change in the membrane potential. Despite the fact that membrane depolarization is commonly associated with excitation, depolarizing GABA/glycine can also produce inhibition, thereby highlighting the dual action of these neurotransmitters. Several considerations must be taken into account in order to allow depolarizing GABA/glycine responses to be excitatory. On the other hand, chloride homeostasis is never steady-state and even small changes of chloride across the membrane can impact the strength of inhibition. This dynamic effect has a direct impact on neuronal excitability and makes its regulation by changes in chloride gradients a highly tunable mechanism. Furthermore, increased excitability may also open a window for system refinement changes, such as synaptic plasticity. Indeed, the regulation of chloride homeostasis may underlie periods of enhanced plasticity, such as during early development. Finally, disruption of chloride gradients arises as a hub for pathology, which is evidenced in multiple disorders in the central nervous system.

scholarly journals Roles of Gasotransmitters in Synaptic Plasticity and Neuropsychiatric Conditions

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Ulfuara Shefa ◽  
Dokyoung Kim ◽  
Min-Sik Kim ◽  
Na Young Jeong ◽  
Junyang Jung
Keyword(s):  
Nervous System ◽  
Synaptic Plasticity ◽  
Neural Plasticity ◽  
Molecular Mechanisms ◽  
Electrical Signal ◽  
The Body ◽  
Major Depressive ◽  
Essential Information ◽  
The Central Nervous System ◽  
Neuropsychiatric Conditions

Synaptic plasticity is important for maintaining normal neuronal activity and proper neuronal functioning in the nervous system. It is crucial for regulating synaptic transmission or electrical signal transduction to neuronal networks, for sharing essential information among neurons, and for maintaining homeostasis in the body. Moreover, changes in synaptic or neural plasticity are associated with many neuropsychiatric conditions, such as schizophrenia (SCZ), bipolar disorder (BP), major depressive disorder (MDD), and Alzheimer’s disease (AD). The improper maintenance of neural plasticity causes incorrect neurotransmitter transmission, which can also cause neuropsychiatric conditions. Gas neurotransmitters (gasotransmitters), such as hydrogen sulfide (H2S), nitric oxide (NO), and carbon monoxide (CO), play roles in maintaining synaptic plasticity and in helping to restore such plasticity in the neuronal architecture in the central nervous system (CNS). Indeed, the upregulation or downregulation of these gasotransmitters may cause neuropsychiatric conditions, and their amelioration may restore synaptic plasticity and proper neuronal functioning and thereby improve such conditions. Understanding the specific molecular mechanisms underpinning these effects can help identify ways to treat these neuropsychiatric conditions.

scholarly journals Significance of GABAA Receptor for Cognitive Function and Hippocampal Pathology

2021 ◽  
Vol 22 (22) ◽  
pp. 12456
Author(s):  
Yuya Sakimoto ◽  
Paw Min-Thein Oo ◽  
Makoto Goshima ◽  
Itsuki Kanehisa ◽  
Yutaro Tsukada ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Gabaa Receptor ◽  
Neuronal Excitability ◽  
Autism Spectrum ◽  
Contextual Learning ◽  
Learning Performance ◽  
Inhibitory Synapses ◽  
Gamma Aminobutyric Acid ◽  
Contextual Memory ◽  
Spatiotemporal Information

The hippocampus is a primary area for contextual memory, known to process spatiotemporal information within a specific episode. Long-term strengthening of glutamatergic transmission is a mechanism of contextual learning in the dorsal cornu ammonis 1 (CA1) area of the hippocampus. CA1-specific immobilization or blockade of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor delivery can impair learning performance, indicating a causal relationship between learning and receptor delivery into the synapse. Moreover, contextual learning also strengthens GABAA (gamma-aminobutyric acid) receptor-mediated inhibitory synapses onto CA1 neurons. Recently we revealed that strengthening of GABAA receptor-mediated inhibitory synapses preceded excitatory synaptic plasticity after contextual learning, resulting in a reduced synaptic excitatory/inhibitory (E/I) input balance that returned to pretraining levels within 10 min. The faster plasticity at inhibitory synapses may allow encoding a contextual memory and prevent cognitive dysfunction in various hippocampal pathologies. In this review, we focus on the dynamic changes of GABAA receptor mediated-synaptic currents after contextual learning and the intracellular mechanism underlying rapid inhibitory synaptic plasticity. In addition, we discuss that several pathologies, such as Alzheimer’s disease, autism spectrum disorders and epilepsy are characterized by alterations in GABAA receptor trafficking, synaptic E/I imbalance and neuronal excitability.

scholarly journals Microglia and Spinal Cord Synaptic Plasticity in Persistent Pain

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Sarah Taves ◽  
Temugin Berta ◽  
Gang Chen ◽  
Ru-Rong Ji
Keyword(s):  
Spinal Cord ◽  
Synaptic Plasticity ◽  
Neural Plasticity ◽  
Persistent Pain ◽  
Spinal Cord Dorsal Horn ◽  
Necrosis Factor Alpha ◽  
Neuronal Interactions ◽  
Spinal Cord Dorsal ◽  
The Central Nervous System ◽  
Factor Alpha

Microglia are regarded as macrophages in the central nervous system (CNS) and play an important role in neuroinflammation in the CNS. Microglial activation has been strongly implicated in neurodegeneration in the brain. Increasing evidence also suggests an important role of spinal cord microglia in the genesis of persistent pain, by releasing the proinflammatory cytokines tumor necrosis factor-alpha (TNFα), Interleukine-1beta (IL-1β), and brain derived neurotrophic factor (BDNF). In this review, we discuss the recent findings illustrating the importance of microglial mediators in regulating synaptic plasticity of the excitatory and inhibitory pain circuits in the spinal cord, leading to enhanced pain states. Insights into microglial-neuronal interactions in the spinal cord dorsal horn will not only further our understanding of neural plasticity but may also lead to novel therapeutics for chronic pain management.

Glial Cells in the Auditory Brainstem

2018 ◽  
pp. 680-706
Author(s):  
Giedre Milinkeviciute ◽  
Karina S. Cramer
Keyword(s):  
Nervous System ◽  
Glial Cells ◽  
Sound Localization ◽  
Auditory Brainstem ◽  
Synaptic Function ◽  
System Function ◽  
Auditory Neurons ◽  
System P ◽  
The Central Nervous System ◽  
Nervous System Function

The auditory brainstem carries out sound localization functions that require an extraordinary degree of precision. While many of the specializations needed for these functions reside in auditory neurons, additional adaptations are made possible by the functions of glial cells. Astrocytes, once thought to have mainly a supporting role in nervous system function, are now known to participate in synaptic function. In the auditory brainstem, they contribute to development of specialized synapses and to mature synaptic function. Oligodendrocytes play critical roles in regulating timing in sound localization circuitry. Microglia enter the central nervous system early in development, and also have important functions in the auditory system’s response to injury. This chapter highlights the unique functions of these non-neuronal cells in the auditory system.

scholarly journals Dysregulation of Astrocyte–Neuronal Communication in Alzheimer’s Disease

2021 ◽  
Vol 22 (15) ◽  
pp. 7887
Author(s):  
Carmen Nanclares ◽  
Andres Mateo Baraibar ◽  
Alfonso Araque ◽  
Paulo Kofuji
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Neuronal Excitability ◽  
Active Role ◽  
Ionic Homeostasis ◽  
Neuronal Communication ◽  
Structural Support

Recent studies implicate astrocytes in Alzheimer’s disease (AD); however, their role in pathogenesis is poorly understood. Astrocytes have well-established functions in supportive functions such as extracellular ionic homeostasis, structural support, and neurovascular coupling. However, emerging research on astrocytic function in the healthy brain also indicates their role in regulating synaptic plasticity and neuronal excitability via the release of neuroactive substances named gliotransmitters. Here, we review how this “active” role of astrocytes at synapses could contribute to synaptic and neuronal network dysfunction and cognitive impairment in AD.

scholarly journals The Function of Selenium in Central Nervous System: Lessons from MsrB1 Knockout Mouse Models

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1372
Author(s):  
Tengrui Shi ◽  
Jianxi Song ◽  
Guanying You ◽  
Yujie Yang ◽  
Qiong Liu ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Synaptic Plasticity ◽  
Mouse Model ◽  
Mouse Models ◽  
Knockout Mouse ◽  
Methionine Sulfoxide ◽  
Methionine Sulfoxide Reductase ◽  
Knockout Mouse Model ◽  
The Central Nervous System

MsrB1 used to be named selenoprotein R, for it was first identified as a selenocysteine containing protein by searching for the selenocysteine insert sequence (SECIS) in the human genome. Later, it was found that MsrB1 is homologous to PilB in Neisseria gonorrhoeae, which is a methionine sulfoxide reductase (Msr), specifically reducing L-methionine sulfoxide (L-Met-O) in proteins. In humans and mice, four members constitute the Msr family, which are MsrA, MsrB1, MsrB2, and MsrB3. MsrA can reduce free or protein-containing L-Met-O (S), whereas MsrBs can only function on the L-Met-O (R) epimer in proteins. Though there are isomerases existent that could transfer L-Met-O (S) to L-Met-O (R) and vice-versa, the loss of Msr individually results in different phenotypes in mice models. These observations indicate that the function of one Msr cannot be totally complemented by another. Among the mammalian Msrs, MsrB1 is the only selenocysteine-containing protein, and we recently found that loss of MsrB1 perturbs the synaptic plasticity in mice, along with the astrogliosis in their brains. In this review, we summarized the effects resulting from Msr deficiency and the bioactivity of selenium in the central nervous system, especially those that we learned from the MsrB1 knockout mouse model. We hope it will be helpful in better understanding how the trace element selenium participates in the reduction of L-Met-O and becomes involved in neurobiology.

scholarly journals Monitoring and Modulating Inflammation-Associated Alterations in Synaptic Plasticity: Role of Brain Stimulation and the Blood–Brain Interface

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 359
Author(s):  
Maximilian Lenz ◽  
Amelie Eichler ◽  
Andreas Vlachos
Keyword(s):  
Synaptic Plasticity ◽  
Brain Stimulation ◽  
Vascular Function ◽  
Neuropsychiatric Symptoms ◽  
Systemic Infection ◽  
Brain Functions ◽  
Blood Brain ◽  
Brain Interface ◽  
The Central Nervous System

Inflammation of the central nervous system can be triggered by endogenous and exogenous stimuli such as local or systemic infection, trauma, and stroke. In addition to neurodegeneration and cell death, alterations in physiological brain functions are often associated with neuroinflammation. Robust experimental evidence has demonstrated that inflammatory cytokines affect the ability of neurons to express plasticity. It has been well-established that inflammation-associated alterations in synaptic plasticity contribute to the development of neuropsychiatric symptoms. Nevertheless, diagnostic approaches and interventional strategies to restore inflammatory deficits in synaptic plasticity are limited. Here, we review recent findings on inflammation-associated alterations in synaptic plasticity and the potential role of the blood–brain interface, i.e., the blood–brain barrier, in modulating synaptic plasticity. Based on recent findings indicating that brain stimulation promotes plasticity and modulates vascular function, we argue that clinically employed non-invasive brain stimulation techniques, such as transcranial magnetic stimulation, could be used for monitoring and modulating inflammation-induced alterations in synaptic plasticity.

scholarly journals Virtual Reality Augmented Feedback Rehabilitation Associated to Action Observation Therapy in Buccofacial Apraxia: Case Report

2021 ◽  
Vol 14 ◽  
pp. 117954762199457
Author(s):  
Daniele Emedoli ◽  
Maddalena Arosio ◽  
Andrea Tettamanti ◽  
Sandro Iannaccone
Keyword(s):  
Virtual Reality ◽  
Neural Plasticity ◽  
Action Observation ◽  
Voluntary Movements ◽  
Augmented Feedback ◽  
Lower Face ◽  
Facial Movements ◽  
Upper Face ◽  
The Central Nervous System ◽  
Buccofacial Apraxia

Background: Buccofacial Apraxia is defined as the inability to perform voluntary movements of the larynx, pharynx, mandible, tongue, lips and cheeks, while automatic or reflexive control of these structures is preserved. Buccofacial Apraxia frequently co-occurs with aphasia and apraxia of speech and it has been reported as almost exclusively resulting from a lesion of the left hemisphere. Recent studies have demonstrated the benefit of treating apraxia using motor training principles such as Augmented Feedback or Action Observation Therapy. In light of this, the study describes the treatment based on immersive Action Observation Therapy and Virtual Reality Augmented Feedback in a case of Buccofacial Apraxia. Participant and Methods: The participant is a right-handed 58-years-old male. He underwent a neurosurgery intervention of craniotomy and exeresis of infra axial expansive lesion in the frontoparietal convexity compatible with an atypical meningioma. Buccofacial Apraxia was diagnosed by a neurologist and evaluated by the Upper and Lower Face Apraxia Test. Buccofacial Apraxia was quantified also by a specific camera, with an appropriately developed software, able to detect the range of motion of automatic face movements and the range of the same movements on voluntary requests. In order to improve voluntary movements, the participant completed fifteen 1-hour rehabilitation sessions, composed of a 20-minutes immersive Action Observation Therapy followed by a 40-minutes Virtual Reality Augmented Feedback sessions, 5 days a week, for 3 consecutive weeks. Results: After treatment, participant achieved great improvements in quality and range of facial movements, performing most of the facial expressions (eg, kiss, smile, lateral angle of mouth displacement) without unsolicited movement. Furthermore, the Upper and Lower Face Apraxia Test showed an improvement of 118% for the Upper Face movements and of 200% for the Lower Face movements. Conclusion: Performing voluntary movement in a Virtual Reality environment with Augmented Feedbacks, in addition to Action Observation Therapy, improved performances of facial gestures and consolidate the activations by the central nervous system based on principles of experience-dependent neural plasticity.

Understanding Neuropathic Pain

CNS Spectrums ◽  
2005 ◽  
Vol 10 (4) ◽  
pp. 298-308 ◽  
Author(s):  
Walter Zieglgänsberger ◽  
Achim Berthele ◽  
Thomas R. Tölle
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neuropathic Pain ◽  
Neuronal Excitability ◽  
Traumatic Injury ◽  
Nerve Fibers ◽  
Cellular Events ◽  
Excitatory Neurotransmitters ◽  
The Central Nervous System ◽  
Activity Dependent

AbstractNeuropathic pain is defined as a chronic pain condition that occurs or persists after a primary lesion or dysfunction of the peripheral or central nervous system. Traumatic injury of peripheral nerves also increases the excitability of nociceptors in and around nerve trunks and involves components released from nerve terminals (neurogenic inflammation) and immunological and vascular components from cells resident within or recruited into the affected area. Action potentials generated in nociceptors and injured nerve fibers release excitatory neurotransmitters at their synaptic terminals such as L-glutamate and substance P and trigger cellular events in the central nervous system that extend over different time frames. Short-term alterations of neuronal excitability, reflected for example in rapid changes of neuronal discharge activity, are sensitive to conventional analgesics, and do not commonly involve alterations in activity-dependent gene expression. Novel compounds and new regimens for drug treatment to influence activity-dependent long-term changes in pain transducing and suppressive systems (pain matrix) are emerging.

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