Mice lacking the transcriptional regulator Bhlhe40 have enhanced neuronal excitability and impaired synaptic plasticity in the hippocampus

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.

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Memory Beyond Synaptic Plasticity: The Role of Intrinsic Neuronal Excitability

Memory Mechanisms in Health and Disease ◽

10.1142/9789814366700_0003 ◽

2012 ◽

pp. 53-80 ◽

Cited By ~ 3

Author(s):

Athanasia Papoutsi ◽

Kyriaki Sidiropoulou ◽

Panayiota Poirazi

Keyword(s):

Synaptic Plasticity ◽

Neuronal Excitability

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RGS7/Gβ5/R7BP complex regulates synaptic plasticity and memory by modulating hippocampal GABABR-GIRK signaling

eLife ◽

10.7554/elife.02053 ◽

2014 ◽

Vol 3 ◽

Cited By ~ 41

Author(s):

Olga Ostrovskaya ◽

Keqiang Xie ◽

Ikuo Masuho ◽

Ana Fajardo-Serrano ◽

Rafael Lujan ◽

...

Keyword(s):

Synaptic Plasticity ◽

Neuronal Excitability ◽

Pyramidal Neurons ◽

Dynamic Range ◽

Gabab Receptor ◽

Girk Channels ◽

Hippocampal Pyramidal Neurons ◽

Inhibitory Neurotransmitter ◽

Membrane Anchoring

In the hippocampus, the inhibitory neurotransmitter GABA shapes the activity of the output pyramidal neurons and plays important role in cognition. Most of its inhibitory effects are mediated by signaling from GABAB receptor to the G protein-gated Inwardly-rectifying K+ (GIRK) channels. Here, we show that RGS7, in cooperation with its binding partner R7BP, regulates GABABR-GIRK signaling in hippocampal pyramidal neurons. Deletion of RGS7 in mice dramatically sensitizes GIRK responses to GABAB receptor stimulation and markedly slows channel deactivation kinetics. Enhanced activity of this signaling pathway leads to decreased neuronal excitability and selective disruption of inhibitory forms of synaptic plasticity. As a result, mice lacking RGS7 exhibit deficits in learning and memory. We further report that RGS7 is selectively modulated by its membrane anchoring subunit R7BP, which sets the dynamic range of GIRK responses. Together, these results demonstrate a novel role of RGS7 in hippocampal synaptic plasticity and memory formation.

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Regulation of Chloride Gradients and Neural Plasticity

Oxford Research Encyclopedia of Neuroscience ◽

10.1093/acrefore/9780190264086.013.238 ◽

2019 ◽

Cited By ~ 2

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.

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Perineuronal Nets in the Superior Olivary Complex

The Oxford Handbook of the Auditory Brainstem ◽

10.1093/oxfordhb/9780190849061.013.12 ◽

2018 ◽

pp. 420-444 ◽

Cited By ~ 1

Author(s):

Markus Morawski ◽

Mandy Sonntag

Keyword(s):

Experimental Data ◽

Extracellular Matrix ◽

Synaptic Plasticity ◽

Neuronal Excitability ◽

Auditory Brainstem ◽

Specific Form ◽

Superior Olivary Complex ◽

Perineuronal Nets ◽

Neuronal Somata ◽

Main Components

This chapter addresses perineuronal nets in the superior olivary complex, a collection of nuclei in the auditory brainstem that are involved in the processing of sound source location. Perineuronal nets, a specific form of extracellular matrix, are believed to control synaptic plasticity. They surround neuronal somata and dendrites of specific types of neurons, among which are many neurons of the superior olivary complex. The chapter describes the distribution of perineuronal nets in the superior olivary complex, focusing on controversial results and discussing underlying reasons. In addition, it considers the development of perineuronal nets and highlights differences between the main components of perineuronal nets, including the proteoglycans aggrecan, brevican, and neurocan. Finally, it introduces current concepts on the function of perineuronal nets that are specifically based on experimental data collected in the superior olivary complex and point to a contribution of perineuronal nets to synaptic transmission and neuronal excitability.

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Spike-timing dependent plasticity beyond synapse - pre- and post-synaptic plasticity of intrinsic neuronal excitability

Frontiers in Synaptic Neuroscience ◽

10.3389/fnsyn.2010.00021 ◽

2010 ◽

Cited By ~ 14

Author(s):

Dominique Debanne

Keyword(s):

Synaptic Plasticity ◽

Neuronal Excitability ◽

Spike Timing ◽

Spike Timing Dependent Plasticity ◽

Dependent Plasticity

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Increased Neuronal Excitability, Synaptic Plasticity, and Learning in Aged Kvβ1.1 Knockout Mice

Current Biology ◽

10.1016/j.cub.2004.10.021 ◽

2004 ◽

Vol 14 (21) ◽

pp. 1907-1915 ◽

Cited By ~ 71

Author(s):

Geoffrey G. Murphy ◽

Nikolai B. Fedorov ◽

K.Peter Giese ◽

Masuo Ohno ◽

Eugenia Friedman ◽

...

Keyword(s):

Synaptic Plasticity ◽

Knockout Mice ◽

Neuronal Excitability

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Significance of GABAA Receptor for Cognitive Function and Hippocampal Pathology

International Journal of Molecular Sciences ◽

10.3390/ijms222212456 ◽

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.

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Neuroplasticity induction using transcranial magnetic stimulation

Psychiatry Neurology and Medical Psychology ◽

10.26565/2312-5675-2019-12-07 ◽

2019 ◽

Keyword(s):

Synaptic Plasticity ◽

Transcranial Magnetic Stimulation ◽

Magnetic Stimulation ◽

Neuronal Excitability ◽

Scientific Data ◽

Dependent Manner ◽

Global Dynamic ◽

Endogenous Dopamine ◽

Ipsilateral Striatum ◽

The Brain

In this article, we have displayed the results of an analysis of modern scientific data on the induction of neuroplasticity using transcranial magnetic stimulation. We presented the multilevel neuroplastic effects of electromagnetic fields caused by transcranial magnetic stimulation (TMS). The authors of the article determined that transcranial magnetic stimulation uses variable magnetic fields to non-invasively stimulate neurons in the brain. The basis of this method is the modulation of neuroplasticity mechanisms with the subsequent reorganization of neural networks. Repeated TMS (rTMS), which is widely used in neurology, affects neurotransmitters and synaptic plasticity, glial cells and the prevention of neuronal death. The neurotrophic effects of rTMS on dendritic growth, as well as growth and neurotrophic factors, are described. An important aspect of the action of TMS is its effect on neuroprotective mechanisms. A neuroimaging study of patients with Parkinson's disease showed that rTMS increased the concentration of endogenous dopamine in the ipsilateral striatum. After rTMS exposure, the number of β-adrenergic receptors in the frontal and cingulate cortex decreases, but the number of NMDA receptors in the ventromedial thalamus, amygdala, and parietal cortex increases. These processes ultimately lead to the induction of prolonged potentiation. In response to rTMS, neuronal excitability changes due to a shift in ion balance around a population of stimulated neurons; this shift manifests itself as altered synaptic plasticity. Combinations of rTMS treatment and pharmacotherapy (e.g., small doses of memantine) may block the alleviating effect during prolonged potentiation. Studies using models of transient ischemic attack and prolonged ischemia have shown that rTMS protects neurons from death and alters the blood flow and metabolism in the brain. It has been demonstrated that TMS has a proven ability to modulate the internal activity of the brain in a frequency-dependent manner, generate contralateral responses, provide, along with the neuromodulating and neurostimulating effect, affect the brain as a global dynamic system.

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