scholarly journals Corticosteroid Regulation of Synaptic Plasticity in the Hippocampus

2010 ◽  
Vol 10 ◽  
pp. 462-469 ◽  
Author(s):  
Nicola Maggio ◽  
Menahem Segal
Keyword(s):  
Synaptic Plasticity ◽  
Stress Level ◽  
Cognitive Functions ◽  
Molecular Mechanisms ◽  
High Stress ◽  
Long Term Potentiation ◽  
Cellular Functions ◽  
Effects Of Stress

Stress, via release of steroid hormones, has been shown to affect several cellular functions in the brain, including synaptic receptors and ion channels. As such, corticosteroids were reported to modulate plasticity, expressed as long-term changes in reactivity to afferent stimulation. The classical view of the effects of stress on synaptic plasticity and cognitive functions assumes an inverted U-shape curve, such that a low stress level facilitates and a high stress level (i.e., corticosterone levels) impairs cognitive functions. This universal view has been challenged recently in a series of studies that show that stress and corticosterone have immediate and opposite effects on the ability to express long-term potentiation (LTP) in the dorsal and ventral sectors of the hippocampus. This differential role of stress may be related to the different functions associated with these sectors of the hippocampus. Herein, we review the known effects of stress hormones on cellular functions and outline the role of molecular mechanisms in stress-related global functions of the hippocampus.

scholarly journals Dissecting the Roles of Kalirin-7/PSD95/GluN2B Interactions in Different Forms of Synaptic Plasticity

2019 ◽  
Author(s):  
Mason L. Yeh ◽  
Jessica R. Yasko ◽  
Eric S. Levine ◽  
Betty A. Eipper ◽  
Richard E. Mains
Keyword(s):  
Synaptic Plasticity ◽  
Knockout Mice ◽  
Molecular Mechanisms ◽  
Postsynaptic Density ◽  
Long Term Potentiation ◽  
Surface Expression ◽  
Multiple Components ◽  
Term Potentiation ◽  
Knockout Animals

AbstractKalirin-7 (Kal7) is a Rac1/RhoG GEF and multidomain scaffold localized to the postsynaptic density which plays an important role in synaptic plasticity. Behavioral and physiological phenotypes observed in the Kal7 knockout mouse are quite specific: genetics of breeding, growth, strength and coordination are normal; Kal7 knockout animals self-administer cocaine far more than normal mice, show exaggerated locomotor responses to cocaine, but lack changes in dendritic spine morphology seen in wildtype mice; Kal7 knockout mice have depressed surface expression of GluN2B receptor subunits and exhibit marked suppression of long-term potentiation and depression in hippocampus, cerebral cortex, and spinal cord; and Kal7 knockout mice have dramatically blunted perception of pain. To address the underlying cellular and molecular mechanisms which are deranged by loss of Kal7, we administered intracellular blocking peptides to acutely change Kal7 function at the synapse, to determine if plasticity deficits in Kal7-/-mice are the product of developmental processes since conception, or could be detected on a much shorter time scale. We found that specific disruption of the interactions of Kal7 with PSD-95 or GluN2B resulted in significant suppression of long-term potentiation and long-term depression. Biochemical approaches indicated that Kal7 interacted with PSD-95 at multiple sites within Kal7.Graphical Table of ContentsThe postsynaptic density is an integral player in receiving, interpreting and storing signals transmitted by presynaptic terminals. The correct molecular composition is crucial for successful expression of synaptic plasticity. Key components of the postsynaptic density include ligand-gated ion channels, structural and binding proteins, and multidomain scaffolding plus enzymatic proteins. These studies address whether the multiple components of the synaptic density bind together in a static or slowly adapting molecular complex, or whether critical interactions are fluid on a minute-to-minute basis.

scholarly journals Chronic neuronal excitation leads to homeostatic suppression of structural long-term potentiation

2021 ◽  
Author(s):  
Hiromi H Ueda ◽  
Aiko Sato ◽  
Maki Onda ◽  
Hideji Murakoshi
Keyword(s):  
Synaptic Plasticity ◽  
Molecular Mechanisms ◽  
Long Term Potentiation ◽  
Homeostatic Plasticity ◽  
Ca1 Neurons ◽  
Downstream Signaling ◽  
Neuronal Excitation ◽  
Term Potentiation ◽  
Hippocampal Ca1

Synaptic plasticity is long-lasting changes in synaptic currents and structure. When neurons are exposed to signals that induce aberrant neuronal excitation, they increase the threshold for the induction of synaptic plasticity, called homeostatic plasticity. To further understand the homeostatic regulation of synaptic plasticity and its molecular mechanisms, we investigated glutamate uncaging/photoactivatable (pa)CaMKII-dependent sLTP induction in hippocampal CA1 neurons after chronic neuronal excitation by GABAA receptor antagonists. The neuronal excitation suppressed the glutamate uncaging-evoked Ca2+ influx and failed to induce sLTP. Single-spine optogenetic stimulation using paCaMKII also failed to induce sLTP, suggesting that CaMKII downstream signaling is impaired in response to chronic neuronal excitation. Furthermore, while the inhibition of Ca2+ influx was protein synthesis-independent, paCaMKII-induced sLTP depended on it. Our findings demonstrate that chronic neuronal excitation suppresses sLTP in two independent ways (i.e., the inhibitions of Ca2+ influx and CaMKII downstream signaling), which may contribute to the robust neuronal protection in excitable environments.

scholarly journals Dissecting the Roles of Kalirin-7/PSD-95/GluN2B Interactions in Different Forms of Synaptic Plasticity

2020 ◽  
Author(s):  
Mason L. Yeh ◽  
Jessica R Yasko ◽  
Eric S. Levine ◽  
Betty A. Eipper ◽  
Richard Mains
Keyword(s):  
Synaptic Plasticity ◽  
Molecular Mechanisms ◽  
Long Term Potentiation ◽  
Surface Expression ◽  
Synaptic Function ◽  
Nucleotide Exchange ◽  
Long Term Depression ◽  
Term Potentiation ◽  
Knockout Animals

Abstract Background: Kalirin-7 (Kal7) is a multidomain scaffold and guanine nucleotide exchange factor localized to the postsynaptic density, where Kal7 is crucial for synaptic plasticity. Kal7 knockout mice exhibit marked suppression of long-term potentiation and long-term depression in hippocampus, cerebral cortex and spinal cord, with depressed surface expression of GluN2B receptor subunits and dramatically blunted perception of pain. Kal7 knockout animals show exaggerated locomotor responses to psychostimulants and self-administer cocaine more enthusiastically than wildtype mice. Results: To address the underlying cellular and molecular mechanisms which are deranged by loss of Kal7, we infused candidate intracellular interfering peptides to acutely challenge the synaptic function(s) of Kal7 with potential protein binding partners, to determine if plasticity deficits in Kal7-/- mice are the product of developmental processes since conception, or could be produced on a much shorter time scale. We demonstrated that these small intracellular peptides disrupted normal long-term potentiation and long-term depression, strongly suggesting that maintenance of established interactions of Kal7 with PSD-95 and/or GluN2B is crucial to synaptic plasticity. Conclusions: Blockade of the Kal7-GluN2B interaction was most effective at blocking long-term potentiation, but had no effect on long-term depression. Biochemical approaches indicated that Kal7 interacted with PSD-95 at multiple sites within Kal7.

scholarly journals A Unique Mouse Model of Early Life Exercise Enables Hippocampal Memory and Synaptic Plasticity

2019 ◽  
Author(s):  
Autumn S. Ivy ◽  
Tim Yu ◽  
Enikö Kramár ◽  
Sonia Parievsky ◽  
Fred Sohn ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Early Life ◽  
Molecular Mechanisms ◽  
Memory Task ◽  
Long Term Potentiation ◽  
Long Term Memory ◽  
Critical Periods ◽  
Juvenile Period ◽  
Cognitive Benefits

AbstractAerobic exercise is a powerful modulator of learning and memory. Molecular mechanisms underlying the cognitive benefits of exercise are well documented in adult rodents. Animal models of exercise targeting specific postnatal periods of hippocampal development and plasticity are lacking. Here we characterize a model of early-life exercise (ELE) in male and female mice designed with the goal of identifying critical periods by which exercise may have a lasting impact on hippocampal memory and synaptic plasticity. Mice freely accessed a running wheel during three postnatal periods: the 4th postnatal week (juvenile ELE, P21-27), 6th postnatal week (adolescent ELE, P35-41), or 4th-6th postnatal weeks (juvenile-adolescent ELE, P21-41). All exercise groups significantly increased their running distances over time. When exposed to a weak learning stimulus, mice that had exercised during the juvenile period were able to form lasting long-term memory for a hippocampus-dependent spatial memory task. Electrophysiological experiments revealed enhanced long-term potentiation in hippocampal CA1 the juvenile-adolescent ELE group only. Furthermore, basal synaptic transmission was significantly increased in all mice that exercised during the juvenile period. Our results suggest early-life exercise can enable hippocampal memory, synaptic plasticity, and basal synaptic physiology when occurring during postnatal periods of hippocampal maturation.

Molecular mechanisms of synaptic consolidation during sleep: BDNF function and dendritic protein synthesis

2005 ◽  
Vol 28 (1) ◽  
pp. 65-66
Author(s):  
Clive R. Bramham
Keyword(s):  
Memory Consolidation ◽  
Molecular Mechanisms ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Dendritic Protein Synthesis ◽  
Mechanisms Of Memory ◽  
Activity Dependent ◽  
Specific Contribution

Insights into the role of sleep in the molecular mechanisms of memory consolidation may come from studies of activity-dependent synaptic plasticity, such as long-term potentiation (LTP). This commentary posits a specific contribution of sleep to LTP stabilization, in which mRNA transported to dendrites during wakefulness is translated during sleep. Brain-derived neurotrophic factor may drive the translation of newly transported and resident mRNA.

Synaptic plasticity in Alzheimer’s disease and healthy aging

2020 ◽  
Vol 31 (3) ◽  
pp. 245-268 ◽  
Author(s):  
Diana Marcela Cuestas Torres ◽  
Fernando P. Cardenas
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Healthy Aging ◽  
Molecular Mechanisms ◽  
Long Term Potentiation ◽  
Cellular Level ◽  
Memory And Learning ◽  
The Individual

AbstractThe strength and efficiency of synaptic connections are affected by the environment or the experience of the individual. This property, called synaptic plasticity, is directly related to memory and learning processes and has been modeled at the cellular level. These types of cellular memory and learning models include specific stimulation protocols that generate a long-term strengthening of the synapses, called long-term potentiation, or a weakening of the said long-term synapses, called long-term depression. Although, for decades, researchers have believed that the main cause of the cognitive deficit that characterizes Alzheimer’s disease (AD) and aging was the loss of neurons, the hypothesis of an imbalance in the cellular and molecular mechanisms of synaptic plasticity underlying this deficit is currently widely accepted. An understanding of the molecular and cellular changes underlying the process of synaptic plasticity during the development of AD and aging will direct future studies to specific targets, resulting in the development of much more efficient and specific therapeutic strategies. In this review, we classify, discuss, and describe the main findings related to changes in the neurophysiological mechanisms of synaptic plasticity in excitatory synapses underlying AD and aging. In addition, we suggest possible mechanisms in which aging can become a high-risk factor for the development of AD and how its development could be prevented or slowed.

scholarly journals Impairments of Long-Term Synaptic Plasticity in the Hippocampus of Young Rats during the Latent Phase of the Lithium-Pilocarpine Model of Temporal Lobe Epilepsy

2021 ◽  
Vol 22 (24) ◽  
pp. 13355
Author(s):  
Tatyana Y. Postnikova ◽  
Georgy P. Diespirov ◽  
Dmitry V. Amakhin ◽  
Elizaveta N. Vylekzhanina ◽  
Elena B. Soboleva ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Long Term Potentiation ◽  
Control Group ◽  
High Frequency Stimulation ◽  
Pilocarpine Model

Status epilepticus (SE) causes persistent abnormalities in the functioning of neuronal networks, often resulting in worsening epileptic seizures. Many details of cellular and molecular mechanisms of seizure-induced changes are still unknown. The lithium–pilocarpine model of epilepsy in rats reproduces many features of human temporal lobe epilepsy. In this work, using the lithium–pilocarpine model in three-week-old rats, we examined the morphological and electrophysiological changes in the hippocampus within a week following pilocarpine-induced seizures. We found that almost a third of the neurons in the hippocampus and dentate gyrus died on the first day, but this was not accompanied by impaired synaptic plasticity at that time. A diminished long-term potentiation (LTP) was observed following three days, and the negative effect of SE on plasticity increased one week later, being accompanied by astrogliosis. The attenuation of LTP was caused by the weakening of N-methyl-D-aspartate receptor (NMDAR)-dependent signaling. NMDAR-current was more than two-fold weaker during high-frequency stimulation in the post-SE rats than in the control group. Application of glial transmitter D-serine, a coagonist of NMDARs, allows the enhancement of the NMDAR-dependent current and the restoration of LTP. These results suggest that the disorder of neuron–astrocyte interactions plays a critical role in the impairment of synaptic plasticity.

Synaptic Plasticity in PTSD and associated Comorbidities: The Function and Mechanism for Diagnostics and Therapy

2019 ◽  
Vol 24 (34) ◽  
pp. 4051-4059 ◽  
Author(s):  
Mei He ◽  
Jing-Xiang Wei ◽  
Min Mao ◽  
Guo-Yan Zhao ◽  
Jun-Jie Tang ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Neurodegenerative Disorders ◽  
Sleep Disturbances ◽  
Molecular Mechanisms ◽  
Wide Spectrum ◽  
Long Term Potentiation ◽  
Synaptic Connections ◽  
Memory Disorder ◽  
Diagnostics And Therapy

The studying of synaptic plasticity, the ability of synaptic connections between neurons to be weakened or strengthened and specifically long-term potentiation (LTP) and long-term depression (LTD), is one of the most active areas of research in neuroscience. The process of synaptic connections playing a crucial role in improving cognitive processes is important to the processing of information in brain. In general, the dysfunction of synaptic plasticity was involved in a wide spectrum of central nervous system (CNS) disorders, including some neurodegenerative disorders. Thus, synaptic plasticity which is a dysfunction reported in neurodegenerative disorders may also be involved in posttraumatic stress disorder (PTSD), an anxiety and/or memory disorder developed after experiencing natural disasters, domestic violence or combat-related trauma. In this review, we mainly focus on discussing the biological function and mechanism for diagnostics and therapy of synaptic plasticity in PTSD and associated comorbidities, such as schizophrenia, depression, sleep disturbances and alcohol dependence, and further studying the molecular mechanisms of PTSD with a particular focus on the LTP/LTD, glutamatergic ligand-receptor systems, voltage-gated calcium channels (VGCCs) and brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB). The summarized function and mechanism of synaptic plasticity in PTSD and its comorbidities may help us further understand PTSD and provide insight into novel neuroplasticity modifying for diagnostics and treatment for PTSD.

scholarly journals MAPK, CREB and zif268 are all required for the consolidation of recognition memory

2003 ◽  
Vol 358 (1432) ◽  
pp. 805-814 ◽  
Author(s):  
Bruno Bozon ◽  
Áine Kelly ◽  
Sheena A. Josselyn ◽  
Alcino J. Silva ◽  
Sabrina Davis ◽  
...  
Keyword(s):  
Recognition Memory ◽  
Molecular Mechanisms ◽  
Long Term Potentiation ◽  
Memory Storage ◽  
Mitogen Activated Protein Kinase ◽  
Early Gene ◽  
Essential Components ◽  
And Storage

There has been nearly a century of interest in the idea that encoding and storage of information in the brain requires changes in the efficacy of synaptic connections between neurons that are activated during learning. Recent research into the molecular mechanisms of long-term potentiation (LTP) has brought about new knowledge that has provided valuable insights into the neural mechanisms of memory storage. The evidence indicates that rapid activation of the genetic machinery can be a key mechanism underlying the enduring modification of neural networks required for the stability of memories. In recent years, a wealth of experimental data has highlighted the importance of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signalling in the regulation of gene transcription in neurons. Here, we briefly review experiments that have shown MAPK/ERK, cAMP response element-binding protein (CREB) and the immediate early gene (IEG) zif268 are essential components of a signalling cascade required for the expression of late phase LTP and of certain forms of long-term memory. We also present experiments in which we have assessed the role of these three molecules in recognition memory. We show that pharmacological blockade of MAPK/ERK phosphorylation, functional inactivation of CREB in an inducible transgenic mouse and inactivation of zif268 in a mutant mouse result in a similar deficit in long-term recognition memory. In the continuing debate about the role of LTP mechanisms in memory, these findings provide an important complement to the suggestion that synaptic changes brought about by LTP and memory consolidation and storage share, at least in part, common underlying molecular mechanisms.

scholarly journals Hippocampal Stratum Oriens Somatostatin-Positive Cells Undergo CB1-Dependent Long-Term Potentiation and Express Endocannabinoid Biosynthetic Enzymes

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1306 ◽  
Author(s):  
Lindsey Friend ◽  
Ryan Williamson ◽  
Collin Merrill ◽  
Scott Newton ◽  
Michael Christensen ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Long Term Potentiation ◽  
Biosynthetic Enzymes ◽  
Type I ◽  
Rt Pcr ◽  
Cellular Expression ◽  
Stratum Oriens ◽  
Term Potentiation

The hippocampus is thought to encode information by altering synaptic strength via synaptic plasticity. Some forms of synaptic plasticity are induced by lipid-based endocannabinoid signaling molecules that act on cannabinoid receptors (CB1). Endocannabinoids modulate synaptic plasticity of hippocampal pyramidal cells and stratum radiatum interneurons; however, the role of endocannabinoids in mediating synaptic plasticity of stratum oriens interneurons is unclear. These feedback inhibitory interneurons exhibit presynaptic long-term potentiation (LTP), but the exact mechanism is not entirely understood. We examined whether oriens interneurons produce endocannabinoids, and whether endocannabinoids are involved in presynaptic LTP. Using patch-clamp electrodes to extract single cells, we analyzed the expression of endocannabinoid biosynthetic enzyme mRNA by reverse transcription and then real-time PCR (RT-PCR). The cellular expression of calcium-binding proteins and neuropeptides were used to identify interneuron subtype. RT-PCR results demonstrate that stratum oriens interneurons express mRNA for both endocannabinoid biosynthetic enzymes and the type I metabotropic glutamate receptors (mGluRs), necessary for endocannabinoid production. Immunohistochemical staining further confirmed the presence of diacylglycerol lipase alpha, an endocannabinoid-synthesizing enzyme, in oriens interneurons. To test the role of endocannabinoids in synaptic plasticity, we performed whole-cell experiments using high-frequency stimulation to induce long-term potentiation in somatostatin-positive cells. This plasticity was blocked by AM-251, demonstrating CB1-dependence. In addition, in the presence of a fatty acid amide hydrolase inhibitor (URB597; 1 µM) and MAG lipase inhibitor (JZL184; 1 µM) that increase endogenous anandamide and 2-arachidonyl glycerol, respectively, excitatory current responses were potentiated. URB597-induced potentiation was blocked by CB1 antagonist AM-251 (2 µM). Collectively, this suggests somatostatin-positive oriens interneuron LTP is CB1-dependent.

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