scholarly journals Astroglia-Derived BDNF and MSK-1 Mediate Experience- and Diet-Dependent Synaptic Plasticity

2020 ◽  
Vol 10 (7) ◽  
pp. 462
Author(s):  
Ulyana Lalo ◽  
Alexander Bogdanov ◽  
Guy W. Moss ◽  
Yuriy Pankratov
Keyword(s):  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Environmental Enrichment ◽  
Aging Brain ◽  
Excitatory Synapses ◽  
Calcium Dependent ◽  
Beneficial Effects ◽  
Cortical Synapses ◽  
The Impact

Experience- and diet-dependent regulation of synaptic plasticity can underlie beneficial effects of active lifestyle on the aging brain. Our previous results demonstrate a key role for brain-derived neurotrophic factor (BDNF) and MSK1 kinase in experience-related homeostatic synaptic scaling. Astroglia has been recently shown to release BDNF via a calcium-dependent mechanism. To elucidate a role for astroglia-derived BDNF in homeostatic synaptic plasticity in the aging brain, we explored the experience- and diet-related alterations of synaptic transmission and plasticity in transgenic mice with impairment of the BDNF/MSK1 pathway (MSK1 kinase dead knock-in mice, MSK1 KD) and impairment of glial exocytosis (dnSNARE mice). We found that prolonged tonic activation of astrocytes caused BDNF-dependent increase in the efficacy of excitatory synapses accompanied by enlargement of synaptic boutons. We also observed that exposure to environmental enrichment (EE) and caloric restriction (CR) enhanced the Ca2+ signalling in cortical astrocytes and strongly up-regulated the excitatory and down-regulated inhibitory synaptic currents in old wild-type mice, thus counterbalancing the impact of ageing on astroglial and synaptic signalling. The EE- and CR-induced up-scaling of excitatory synaptic transmission in neocortex was accompanied by the enhancement of long-term synaptic potentiation. Importantly, effects of EE and CR on synaptic transmission and plasticity was significantly reduced in the MSK1 KD and dnSNARE mice. Combined, our results suggest that astroglial release of BDNF is important for the homeostatic regulation of cortical synapses and beneficial effects of EE and CR on synaptic transmission and plasticity in aging brain.

scholarly journals Role for Astroglia-Derived BDNF and MSK1 in Homeostatic Synaptic Plasticity

Neuroglia ◽  
2018 ◽  
Vol 1 (2) ◽  
pp. 381-394 ◽  
Author(s):  
Ulyana Lalo ◽  
Alexander Bogdanov ◽  
Guy W. J. Moss ◽  
Bruno G. Frenguelli ◽  
Yuriy Pankratov
Keyword(s):  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Environmental Enrichment ◽  
Synaptic Currents ◽  
Beneficial Effects ◽  
Homeostatic Synaptic Plasticity ◽  
Significant Deficit ◽  
Synaptic Boutons ◽  
The Impact ◽  
Ageing Brain

Homeostatic scaling of synaptic strength in response to environmental stimuli may underlie the beneficial effects of an active lifestyle on brain function. Our previous results highlighted a key role for brain-derived neurotrophic factor (BDNF) and mitogen- and stress-activated protein kinase 1 (MSK1) in experience-related homeostatic synaptic plasticity. Astroglia have recently been shown to serve as an important source of BDNF. To elucidate a role for astroglia-derived BDNF, we explored homeostatic synaptic plasticity in transgenic mice with an impairment in the BDNF/MSK1 pathway (MSK1 kinase dead knock-in (KD) mice) and impairment of glial exocytosis (dnSNARE mice). We observed that prolonged tonic activation of astrocytes caused BDNF-dependent upregulation of excitatory synaptic currents accompanied by enlargement of synaptic boutons. We found that exposure to environmental enrichment (EE) and caloric restriction (CR) strongly upregulated excitatory but downregulated inhibitory synaptic currents in old wild-type mice, thus counterbalancing the impact of ageing on synaptic transmission. In parallel, EE and CR enhanced astrocytic Ca2+-signalling. Importantly, we observed a significant deficit in the effects of EE and CR on synaptic transmission in the MSK1 KD and dnSNARE mice. Combined, our results strongly support the importance of astrocytic exocytosis of BDNF for the beneficial effects of EE and CR on synaptic transmission and plasticity in the ageing brain.

scholarly journals Basal Synaptic Transmission and Long-Term Plasticity at CA3-CA1 Synapses Are Unaffected in Young Adult PINK1-Deficient Rats

2021 ◽  
Vol 15 ◽  
Author(s):  
Adeel A. Memon ◽  
Micah E. Bagley ◽  
Rose B. Creed ◽  
Amy W. Amara ◽  
Matthew S. Goldberg ◽  
...  
Keyword(s):  
Young Adult ◽  
Synaptic Transmission ◽  
Projection Neurons ◽  
Excitatory Postsynaptic Potential ◽  
Excitatory Synapses ◽  
Motor Symptoms ◽  
Excitatory Transmission ◽  
The Impact ◽  
Basal Synaptic Transmission

Loss of function mutations in PARK6, the gene that encodes the protein PTEN-induced kinase 1 (PINK1), cause autosomal recessive familial Parkinson’s disease (PD). While PD is clinically diagnosed by its motor symptoms, recent studies point to the impact of non-motor symptoms, including cognitive dysfunction in the early pre-motor stages of the disease (Aarsland et al., 2004; Chaudhuri and Schapira, 2009). As the hippocampus is a key structure for learning and memory, this study aimed to determine whether synaptic transmission is affected at CA3-CA1 excitatory synapses in PINK1 knockout rats at an age when we recently reported a gain of function at excitatory synapses onto spiny projection neurons in the dorsal striatum (Creed et al., 2020) and when motor symptoms are beginning to appear (Dave et al., 2014). Using extracellular dendritic field excitatory postsynaptic potential recordings at CA3-CA1 synapses in dorsal hippocampus 4-to 5- month old PINK1 KO rats and wild-type littermate controls, we observed no detectable differences in the strength of basal synaptic transmission, paired-pulse facilitation, or long-term potentiation. Our results suggest that loss of PINK1 protein does not cause a general dysfunction of excitatory transmission throughout the brain at this young adult age when excitatory transmission is abnormal in the striatum.

Functional Characterization of Des-IGF-1 Action at Excitatory Synapses in the CA1 Region of Rat Hippocampus

2005 ◽  
Vol 94 (1) ◽  
pp. 247-254 ◽  
Author(s):  
Melinda M. Ramsey ◽  
Michelle M. Adams ◽  
Olusegun J. Ariwodola ◽  
William E. Sonntag ◽  
Jeff L. Weiner
Keyword(s):  
Synaptic Transmission ◽  
Hippocampal Slices ◽  
Functional Characterization ◽  
Excitatory Postsynaptic Potential ◽  
Excitatory Synapses ◽  
Aged Rats ◽  
Cognitive Improvement ◽  
Ca1 Region

Insulin-like growth factor-1 (IGF-1) and growth hormone play a major role in the growth and development of tissues throughout the mammalian body. Plasma IGF-1 concentrations peak during puberty and decline with age. We have determined that chronic treatments to restore plasma IGF-1 concentrations to adult levels attenuate spatial learning deficits in aged rats, but little is known of the acute actions of IGF-1 in the brain. To this end, we utilized hippocampal slices from young Sprague-Dawley rats to characterize the acute effects of des-IGF-1 on excitatory synaptic transmission in the CA1 region. We observed a 40% increase in field excitatory postsynaptic potential (fEPSP) slope with application of des-IGF-1 (40 ng/ml) and used whole cell patch-clamp recordings to determine that this enhancement was due to a postsynaptic mechanism involving α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate (AMPA) but not N-methyl-d-aspartate receptors. Furthermore, the enhancement was completely blocked by the broad-spectrum tyrosine kinase inhibitor, genistein (220 μM), and significantly reduced by the PI3K blockers wortmannin (1 μM) and 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (10 μM), suggesting that the effect was predominantly dependent on PI3K activation. This characterization of the acute actions of des-IGF-1 at hippocampal excitatory synapses may provide insight into the mechanism by which long-term increases in plasma IGF-1 impart cognitive benefits in aged rats. Increases in AMPA receptor-mediated synaptic transmission may contribute directly to cognitive improvement or initiate long-term changes in synthesis of proteins such as brain-derived neurotrophic factor that are important to learning and memory.

scholarly journals Chemical LTD, but not LTP, induces transient accumulation of gelsolin in dendritic spines

2019 ◽  
Vol 400 (9) ◽  
pp. 1129-1139 ◽  
Author(s):  
Iryna Hlushchenko ◽  
Pirta Hotulainen
Keyword(s):  
Synaptic Plasticity ◽  
Dendritic Spines ◽  
Hippocampal Neurons ◽  
Long Term Potentiation ◽  
Excitatory Synapses ◽  
Signal Molecule ◽  
Brain Functions ◽  
Dendritic Shaft ◽  
Term Potentiation

Abstract Synaptic plasticity underlies central brain functions, such as learning. Ca2+ signaling is involved in both strengthening and weakening of synapses, but it is still unclear how one signal molecule can induce two opposite outcomes. By identifying molecules, which can distinguish between signaling leading to weakening or strengthening, we can improve our understanding of how synaptic plasticity is regulated. Here, we tested gelsolin’s response to the induction of chemical long-term potentiation (cLTP) or long-term depression (cLTD) in cultured rat hippocampal neurons. We show that gelsolin relocates from the dendritic shaft to dendritic spines upon cLTD induction while it did not show any relocalization upon cLTP induction. Dendritic spines are small actin-rich protrusions on dendrites, where LTD/LTP-responsive excitatory synapses are located. We propose that the LTD-induced modest – but relatively long-lasting – elevation of Ca2+ concentration increases the affinity of gelsolin to F-actin. As F-actin is enriched in dendritic spines, it is probable that increased affinity to F-actin induces the relocalization of gelsolin.

Remodeling of astrocytes, a prerequisite for synapse turnover in the adult brain? Insights from the oxytocin system of the hypothalamus

2006 ◽  
Vol 290 (5) ◽  
pp. R1175-R1182 ◽  
Author(s):  
Dionysia T. Theodosis ◽  
Andrei Trailin ◽  
Dominique A. Poulain
Keyword(s):  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Neuronal Activity ◽  
Adult Brain ◽  
Synaptic Connectivity ◽  
Excitatory Synapses ◽  
Neuronal Function ◽  
Physiological Conditions ◽  
Baseline Levels ◽  
Activity Dependent

Neurons, including their synapses, are generally ensheathed by fine processes of astrocytes, but this glial coverage can be altered under different physiological conditions that modify neuronal activity. Changes in synaptic connectivity accompany astrocytic transformations so that an increased number of synapses are associated with reduced astrocytic coverage of postsynaptic elements, whereas synaptic numbers are reduced on reestablishment of glial coverage. A system that exemplifies activity-dependent structural synaptic plasticity in the adult brain is the hypothalamo-neurohypophysial system, and in particular, its oxytocin component. Under strong, prolonged activation (parturition, lactation, chronic dehydration), extensive portions of somatic and dendritic surfaces of magnocellular oxytocin neurons are freed of intervening astrocytic processes and become directly juxtaposed. Concurrently, they are contacted by an increased number of inhibitory and excitatory synapses. Once stimulation is over, astrocytic processes again cover oxytocinergic surfaces and synaptic numbers return to baseline levels. Such observations indicate that glial ensheathment of neurons is of consequence to neuronal function, not only directly, for example by modifying synaptic transmission, but indirectly as well, by preparing neuronal surfaces for synapse turnover.

scholarly journals Early low-level developmental arsenic exposure impacts mouse hippocampal synaptic function

2021 ◽  
Author(s):  
Karl F Foley ◽  
Daniel Barnett ◽  
Deborah A Cory-Slechta ◽  
Houhui Xia
Keyword(s):  
Synaptic Transmission ◽  
Hippocampal Slices ◽  
Arsenic Exposure ◽  
Long Term Potentiation ◽  
Epidemiological Studies ◽  
Synaptic Function ◽  
Learning Deficits ◽  
Term Potentiation ◽  
The Impact

Background: Arsenic is a well-established carcinogen known to increase all-cause mortality, but its effects on the central nervous system are less well understood. Recent epidemiological studies suggest that early life exposure to arsenic is associated with learning deficits and behavioral changes, and increased arsenic exposure continues to affect an estimated 200 million individuals worldwide. Previous studies on arsenic exposure and synaptic function have demonstrated a decrease in synaptic transmission and long-term potentiation in adult rodents, but have relied on in vitro or extended exposure in adulthood. Therefore, little is known about the effect of arsenic exposure in development. Objective: Here, we studied the effects of gestational and early developmental arsenic exposure in juvenile mice. Specifically, our objective was to investigate the impact of arsenic exposure on synaptic transmission and plasticity in the hippocampus. Methods: C57BL/6 females were exposed to arsenic (0, 50ppb, 36ppm) in their drinking water two weeks prior to mating and continued to be exposed to arsenic throughout gestation and after parturition. We then performed field recordings in acute hippocampal slices from the juvenile offspring prior to weaning (P17-P23). In this paradigm, the juvenile mice are only exposed to arsenic in utero and via the mothers milk. Results: High (36ppm) and relatively low (50ppb) arsenic exposure both lead to decreased basal synaptic transmission in the hippocampus of juvenile mice. There was a mild decrease in paired-pulse facilitation in juvenile mice exposed to high, but not low, arsenic, suggesting the alterations in synaptic transmission are primarily post-synaptic. Finally, high developmental arsenic exposure led to a significant increase in long-term potentiation. Discussion: These results suggest that indirect, ecologically-relevant arsenic exposure in early development impacts hippocampal synaptic transmission and plasticity that could underlie learning deficits reported in epidemiological studies.

scholarly journals Synergy between vesicular and non-vesicular gliotransmission regulates synaptic plasticity and working memory

2021 ◽  
Author(s):  
Ulyana Lalo ◽  
Seyed Rasooli-Nejad ◽  
Alexander Bogdanov ◽  
Lorenzo More ◽  
Wuhyun Koh ◽  
...  
Keyword(s):  
Working Memory ◽  
Synaptic Plasticity ◽  
Small Molecule ◽  
Environmental Enrichment ◽  
Pyramidal Neurons ◽  
Active Element ◽  
Spatial Working Memory ◽  
Phasic Response ◽  
Cortical Astrocytes

Astrocytes are an active element of brain signalling, capable of release of small molecule gliotransmitters by vesicular and channel-mediated mechanisms. However, specific physiological roles of astroglial exocytosis of glutamate and D-Serine remain controversial. Our data demonstrate that cortical astrocytes can release glutamate and D-Serine by combination of SNARE-dependent exocytosis and non-vesicular mechanisms dependent on TREK-1 and Best1 channels. Astrocyte-derived glutamate and D-serine elicited complex multicomponent phasic response in neocortical pyramidal neurons, which is mediated by extra-synaptic GluN2B receptors. Impairment of either pathway of gliotransmission (in the TREK1 KO, Best-1 KO or dnSNARE mice) strongly affected the NMDAR-dependent long-term synaptic plasticity in the hippocampus and neocortex. Moreover, impairment of astroglial exocytosis in dnSNARE mice led to the deficit in the spatial working memory which was rescued by environmental enrichment. We conclude that synergism between vesicular and non-vesicular gliotransmission is crucial for astrocyte-neuron communication and astroglia-driven regulation of synaptic plasticity and memory.

scholarly journals Hippocampal Somatostatin Interneurons, Long-Term Synaptic Plasticity and Memory

2021 ◽  
Vol 15 ◽  
Author(s):  
Eve Honoré ◽  
Abdessattar Khlaifia ◽  
Anthony Bosson ◽  
Jean-Claude Lacaille
Keyword(s):  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Inhibitory Neurons ◽  
Inhibitory Interneurons ◽  
Excitatory Synapses ◽  
Dynamic Regulation ◽  
Hippocampal Network ◽  
Hippocampal Networks ◽  
Hippocampal Structure

A distinctive feature of the hippocampal structure is the diversity of inhibitory interneurons. These complex inhibitory interconnections largely contribute to the tight modulation of hippocampal circuitry, as well as to the formation and coordination of neuronal assemblies underlying learning and memory. Inhibitory interneurons provide more than a simple transitory inhibition of hippocampal principal cells (PCs). The synaptic plasticity of inhibitory neurons provides long-lasting changes in the hippocampal network and is a key component of memory formation. The dendrite targeting interneurons expressing the peptide somatostatin (SOM) are particularly interesting in this regard because they display unique long-lasting synaptic changes leading to metaplastic regulation of hippocampal networks. In this article, we examine the actions of the neuropeptide SOM on hippocampal cells, synaptic plasticity, learning, and memory. We address the different subtypes of hippocampal SOM interneurons. We describe the long-term synaptic plasticity that takes place at the excitatory synapses of SOM interneurons, its singular induction and expression mechanisms, as well as the consequences of these changes on the hippocampal network, learning, and memory. We also review evidence that astrocytes provide cell-specific dynamic regulation of inhibition of PC dendrites by SOM interneurons. Finally, we cover how, in mouse models of Alzheimer’s disease (AD), dysfunction of plasticity of SOM interneuron excitatory synapses may also contribute to cognitive impairments in brain disorders.

scholarly journals Species-specific differences in synaptic transmission and plasticity

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Prateep Beed ◽  
Saikat Ray ◽  
Laura Moreno Velasquez ◽  
Alexander Stumpf ◽  
Daniel Parthier ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Synaptic Transmission ◽  
Mossy Fiber ◽  
Mossy Fibers ◽  
Evolutionary Divergence ◽  
Short Term Plasticity ◽  
Species Specific ◽  
The Brain ◽  
Lower Expression

Abstract Synaptic transmission and plasticity in the hippocampus are integral factors in learning and memory. While there has been intense investigation of these critical mechanisms in the brain of rodents, we lack a broader understanding of the generality of these processes across species. We investigated one of the smallest animals with conserved hippocampal macroanatomy—the Etruscan shrew, and found that while synaptic properties and plasticity in CA1 Schaffer collateral synapses were similar to mice, CA3 mossy fiber synapses showed striking differences in synaptic plasticity between shrews and mice. Shrew mossy fibers have lower long term plasticity compared to mice. Short term plasticity and the expression of a key protein involved in it, synaptotagmin 7 were also markedly lower at the mossy fibers in shrews than in mice. We also observed similar lower expression of synaptotagmin 7 in the mossy fibers of bats that are evolutionarily closer to shrews than mice. Species specific differences in synaptic plasticity and the key molecules regulating it, highlight the evolutionary divergence of neuronal circuit functions.

Sign in / Sign up

Export Citation Format

Share Document