scholarly journals Exercise-induced enhancement of synaptic function triggered by the inverse BAR protein, Mtss1L

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Christina Chatzi ◽  
Yingyu Zhang ◽  
Wiiliam D Hendricks ◽  
Yang Chen ◽  
Eric Schnell ◽  
...  
Keyword(s):  
Granule Cells ◽  
Membrane Curvature ◽  
Synaptic Function ◽  
Voluntary Exercise ◽  
Excitatory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Underlying Mechanisms ◽  
Exercise Induced ◽  
Activity Dependent

Exercise is a potent enhancer of learning and memory, yet we know little of the underlying mechanisms that likely include alterations in synaptic efficacy in the hippocampus. To address this issue, we exposed mice to a single episode of voluntary exercise, and permanently marked activated mature hippocampal dentate granule cells using conditional Fos-TRAP mice. Exercise-activated neurons (Fos-TRAPed) showed an input-selective increase in dendritic spines and excitatory postsynaptic currents at 3 days post-exercise, indicative of exercise-induced structural plasticity. Laser-capture microdissection and RNASeq of activated neurons revealed that the most highly induced transcript was Mtss1L, a little-studied I-BAR domain-containing gene, which we hypothesized could be involved in membrane curvature and dendritic spine formation. shRNA-mediated Mtss1L knockdown in vivo prevented the exercise-induced increases in spines and excitatory postsynaptic currents. Our results link short-term effects of exercise to activity-dependent expression of Mtss1L, which we propose as a novel effector of activity-dependent rearrangement of synapses.

scholarly journals Exercise-induced enhancement of synaptic function triggered by the inverse BAR protein, Mtss1L

2019 ◽  
Author(s):  
Christina Chatzi ◽  
Gina Zhang ◽  
William Hendricks ◽  
Yang Chen ◽  
Eric Schnell ◽  
...  
Keyword(s):  
Granule Cells ◽  
Membrane Curvature ◽  
Synaptic Function ◽  
Adult Brain ◽  
Voluntary Exercise ◽  
Excitatory Postsynaptic Currents ◽  
Dentate Granule Cells ◽  
Postsynaptic Currents ◽  
Exercise Induced ◽  
Activity Dependent

AbstractExercise is a potent enhancer of learning and memory, yet we know little of the underlying mechanisms that likely include alterations in synaptic efficacy in the hippocampus. To address this issue, we exposed mice to a single episode of voluntary exercise, and permanently marked mature hippocampal dentate granule cells that were specifically activated during exercise using conditional Fos-TRAP mice. Only a few dentate granule cells were active at baseline, but two hours of voluntary exercise markedly increased the number of activated neurons. Activated neurons (Fos-TRAPed) showed an input-selective increase in dendritic spines and excitatory postsynaptic currents at 3 days post-exercise, indicative of exercise-induced structural plasticity. Laser-capture microdissection and RNASeq of activated neurons revealed that the most highly induced transcript was Mtss1L, a little-studied gene in the adult brain. Overexpression of Mtss1L in neurons increased spine density, leading us to hypothesize that its I-BAR domain initiated membrane curvature and dendritic spine formation. shRNA-mediated Mtss1L knockdown in vivo prevented the exercise-induced increases in spines and excitatory postsynaptic currents. Our results link short-term effects of exercise to activity-dependent expression of Mtss1L, which we propose as a novel effector of activity-dependent rearrangement of synapses.One Sentence SummarySingle episodes of voluntary exercise induced a functional increase in hippocampal synapses mediated by activity-dependent expression of the BAR protein Mtss1L, acting as a novel early effector of synapse formation.

scholarly journals High Ratio of Synaptic Excitation to Synaptic Inhibition in Hilar Ectopic Granule Cells of Pilocarpine-Treated Rats

2010 ◽  
Vol 104 (6) ◽  
pp. 3293-3304 ◽  
Author(s):  
Ren-Zhi Zhan ◽  
Olga Timofeeva ◽  
J. Victor Nadler
Keyword(s):  
Status Epilepticus ◽  
Granule Cell ◽  
Granule Cells ◽  
Mossy Fiber ◽  
High Ratio ◽  
Synaptic Function ◽  
Excitatory Postsynaptic Currents ◽  
Inhibitory Postsynaptic Currents ◽  
Synaptic Excitation ◽  
Postsynaptic Currents

After experimental status epilepticus, many dentate granule cells born into the postseizure environment migrate aberrantly into the dentate hilus. Hilar ectopic granule cells (HEGCs) have also been found in persons with epilepsy. These cells exhibit a high rate of spontaneous activity, which may enhance seizure propagation. Electron microscopic studies indicated that HEGCs receive more recurrent mossy fiber innervation than normotopic granule cells in the same animals but receive much less inhibitory innervation. This study used hippocampal slices prepared from rats that had experienced pilocarpine-induced status epilepticus to test the hypothesis that an imbalance of synaptic excitation and inhibition contributes to the hyperexcitability of HEGCs. Mossy fiber stimulation evoked a much smaller GABAA receptor–mediated inhibitory postsynaptic currents (IPSC) in HEGCs than in normotopic granule cells from either control rats or rats that had experienced status epilepticus. However, recurrent mossy fiber-evoked excitatory postsynaptic currents (EPSCs) of similar size were recorded from HEGCs and normotopic granule cells in status epilepticus–experienced rats. HEGCs exhibited the highest frequency of miniature excitatory postsynaptic currents (mEPSCs) and the lowest frequency of miniature inhibitory postsynaptic currents (mIPSCs) of any granule cell group. On average, both mEPSCs and mIPSCs were of higher amplitude, transferred more charge per event, and exhibited slower kinetics in HEGCs than in granule cells from control rats. Charge transfer per unit time in HEGCs was greater for mEPSCs and much less for mIPSCs than in the normotopic granule cell groups. A high ratio of excitatory to inhibitory synaptic function probably accounts, in part, for the hyperexcitability of HEGCs.

scholarly journals Influences of Morphine on the Spontaneous and Evoked Excitatory Postsynaptic Currents in Lateral Amygdala of Rats

2016 ◽  
pp. 165-169 ◽  
Author(s):  
J.-J. ZHANG ◽  
X.-D. LIU ◽  
L.-C. YU
Keyword(s):  
Synaptic Transmission ◽  
Excitatory Synaptic Transmission ◽  
Morphine Treatment ◽  
Lateral Amygdala ◽  
Excitatory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Whole Cell Patch Clamp ◽  
The Central Nervous System ◽  
Underlying Mechanisms

Acute morphine exposure induces antinociceptive activity, but the underlying mechanisms in the central nervous system are unclear. Using whole-cell patch clamp recordings, we explore the role of morphine in the modulation of excitatory synaptic transmission in lateral amygdala neurons of rats. The results demonstrate that perfusion of 10 μM of morphine to the lateral amygdala inhibits the discharge frequency significantly. We further find that there are no significant influences of morphine on the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs). Interestingly, morphine shows no marked influence on the evoked excitatory postsynaptic currents (eEPSCs) in the lateral amygdala neurons. These results indicate that acute morphine treatment plays an important role in the modulation on the excitatory synaptic transmission in lateral amygdala neurons of rats.

scholarly journals The Perils of Navigating Activity-Dependent Alternative Splicing of Neurexins

2021 ◽  
Vol 14 ◽  
Author(s):  
Kif Liakath-Ali ◽  
Thomas C. Südhof
Keyword(s):  
Synaptic Plasticity ◽  
Alternative Splicing ◽  
Synaptic Function ◽  
Plasticity Mechanism ◽  
Alternatively Spliced ◽  
Apparent Shift ◽  
Activity Dependent ◽  
Dependent Mechanism ◽  
Synaptic Responses

Neurexins are presynaptic cell-adhesion molecules essential for synaptic function that are expressed in thousands of alternatively spliced isoforms. Recent studies suggested that alternative splicing at splice site 4 (SS4) of Nrxn1 is tightly regulated by an activity-dependent mechanism. Given that Nrxn1 alternative splicing at SS4 controls NMDA-receptor-mediated synaptic responses, activity-dependent SS4 alternative splicing would suggest a new synaptic plasticity mechanism. However, conflicting results confound the assessment of neurexin alternative splicing, prompting us to re-evaluate this issue. We find that in cortical cultures, membrane depolarization by elevated extracellular K+-concentrations produced an apparent shift in Nrxn1-SS4 alternative splicing by inducing neuronal but not astroglial cell death, resulting in persistent astroglial Nrxn1-SS4+ expression and decreased neuronal Nrxn1-SS4– expression. in vivo, systemic kainate-induced activation of neurons in the hippocampus produced no changes in Nrxn1-SS4 alternative splicing. Moreover, focal kainate injections into the mouse cerebellum induced small changes in Nrxn1-SS4 alternative splicing that, however, were associated with large decreases in Nrxn1 expression and widespread DNA damage. Our results suggest that although Nrxn1-SS4 alternative splicing may represent a mechanism of activity-dependent synaptic plasticity, common procedures for testing this hypothesis are prone to artifacts, and more sophisticated approaches will be necessary to test this important question.

SDF-1α induces chemotaxis and enhances Sonic hedgehog-induced proliferation of cerebellar granule cells

Development ◽  
2001 ◽  
Vol 128 (11) ◽  
pp. 1971-1981 ◽  
Author(s):  
Robyn S. Klein ◽  
Joshua B. Rubin ◽  
Hilary D. Gibson ◽  
Elliot N. DeHaan ◽  
Xavier Alvarez-Hernandez ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Granule Cell ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Cell Number ◽  
Calcium Flux ◽  
Neuronal Responses ◽  
And Migration ◽  
Activity Dependent

The chemokine SDF-1α (CXC12) and its receptor CXCR4 have been shown to play a role in the development of normal cerebellar cytoarchitecture. We report here that SDF-1α both induces chemotactic responses in granule precursor cells and enhances granule cell proliferative responses to Sonic hedgehog. Chemotactic and proliferative responses to SDF-1α are greater in granule cells obtained from cerebella of animals in the first postnatal week, coinciding with the observed in vivo peak in cerebellar CXCR4 expression. SDF-1α activation of neuronal CXCR4 differs from activation of CXCR4 in leukocytes in that SDF-1α-induced calcium flux is activity dependent, requiring predepolarization with KCl or pretreatment with glutamate. However, as is the case in leukocytes, neuronal responses to SDF-1α are all abolished by pretreatment of granule cells with pertussis toxin, suggesting they occur through Gαi activation. In conclusion, SDF-1α plays a role in two important processes of granule cell maturation – proliferation and migration – assisting in the achievement of appropriate cell number and position in the cerebellar cortex.

scholarly journals Synaptic Inputs to Granule Cells of the Dorsal Cochlear Nucleus

2008 ◽  
Vol 99 (1) ◽  
pp. 208-219 ◽  
Author(s):  
Veeramuthu Balakrishnan ◽  
Laurence O. Trussell
Keyword(s):  
Granule Cell ◽  
Cochlear Nucleus ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Dorsal Cochlear Nucleus ◽  
Excitatory Postsynaptic Currents ◽  
Synaptic Inputs ◽  
Postsynaptic Currents ◽  
Cell Circuit

The mammalian dorsal cochlear nucleus (DCN) integrates auditory nerve input with nonauditory signals via a cerebellar-like granule cell circuit. Although granule cells carry nonauditory information to the DCN, almost nothing is known about their physiology. Here we describe electrophysiological features of synaptic inputs to granule cells in the DCN by in vitro patch-clamp recordings from P12 to P22 rats. Granule cells ranged from 6 to 8 μm in cell body diameter and had high-input resistance. Excitatory postsynaptic currents consisted of both AMPA receptor-mediated and N-methyl-d-aspartate receptor-mediated currents. Synaptically evoked excitatory postsynaptic currents ranged from −25 to −140 pA with fast decay time constants. Synaptic stimulation evoked both short- and long-latency synaptic responses that summated to spike threshold, indicating the presence of a polysynaptic excitatory pathway in the granule cell circuit. Synaptically evoked inhibitory postsynaptic currents in Cl−-loaded cells ranged from −30 to −1,021 pA and were mediated by glycine and, to a lesser extent, GABAA receptors. Unlike cerebellar granule cells, DCN granule cells lacked tonic inhibition by GABA. The glycinergic synaptic conductance was mediated by heteromeric glycine receptors and was far stronger than the glutamatergic conductance, suggesting that glycinergic neurons may act to gate nonauditory signals in the DCN.

scholarly journals Activity-dependent Increases in Local Oxygen Consumption Correlate with Postsynaptic Currents in the Mouse Cerebellum In Vivo

2011 ◽  
Vol 31 (50) ◽  
pp. 18327-18337 ◽  
Author(s):  
C. Mathiesen ◽  
K. Caesar ◽  
K. Thomsen ◽  
T. M. Hoogland ◽  
B. M. Witgen ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Postsynaptic Currents ◽  
Mouse Cerebellum ◽  
Activity Dependent ◽  
Local Oxygen

Effects of Halothane on Glutamate Receptor-mediated Excitatory Postsynaptic Currents

1995 ◽  
Vol 83 (1) ◽  
pp. 109-119. ◽  
Author(s):  
Misha Perouansky ◽  
Dimitri Baranov ◽  
Michael Salman ◽  
Yoel Yaari
Keyword(s):  
Glutamate Receptor ◽  
Glutamate Release ◽  
Pyramidal Cells ◽  
Receptor Subtype ◽  
Excitatory Postsynaptic Currents ◽  
Ca1 Pyramidal Cells ◽  
Postsynaptic Currents ◽  
High Concentrations

Background The effects of halothane on excitatory synaptic transmission in the central nervous system of mammals have been studied in vivo and in vitro in several investigations with partially contradicting results. Direct measurements of the effects of halothane on isolated glutamate receptor-mediated (glutamatergic) excitatory postsynaptic currents (EPSCs), however, have not been reported to date. Methods The effects of halothane on glutamatergic EPSCs were studied in vitro by using tight-seal, whole-cell recordings from CA1 pyramidal cells in thin slices from the adult mouse hippocampus. The EPSCs were pharmacologically isolated into their non-N-methyl-D-aspartate (non-NMDA) and NMDA receptor-mediated components by using selective antagonists. The effects of halothane on EPSC amplitude and kinetics were analyzed at various membrane potentials and were compared with its effects on currents evoked by exogenously applied glutamatergic agonists. Results Halothane (0.2-5.1%; 0.37-2.78 mM) reversibly blocked non-NMDA and NMDA EPSCs. This effect was voltage independent; concentrations producing 50% inhibition were 0.87% (0.66 mM) and 0.69% (0.57 mM), respectively. Currents induced by bath-applied glutamatergic agonists were not affected even by the high concentrations of halothane. Conclusions Halothane depresses glutamatergic EPSCs irrespective of receptor subtype, most likely by inhibition of glutamate release.

scholarly journals Beneficial effect of voluntary physical exercise in Plakophilin2 transgenic mice

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252649
Author(s):  
Karin P. Hammer ◽  
Julian Mustroph ◽  
Teresa Stauber ◽  
Walter Birchmeier ◽  
Stefan Wagner ◽  
...  
Keyword(s):  
Beneficial Effect ◽  
Structural Changes ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Voluntary Exercise ◽  
Loss Of Function ◽  
Functional Development ◽  
Increased Risk ◽  
Exercise Induced

Arrhythmogenic right ventricular cardiomyopathy is a hereditary, rare disease with an increased risk for sudden cardiac death. The disease-causing mutations are located within the desmosomal complex and the highest incidence is found in plakophilin2. However, there are other factors playing a role for the disease progression unrelated to the genotype such as inflammation or exercise. Competitive sports have been identified as risk factor, but the type and extend of physical activity as cofactor for arrhythmogenesis remains under debate. We thus studied the effect of light voluntary exercise on cardiac health in a mouse model. Mice with a heterozygous PKP2 loss-of-function mutation were given the option to exercise in a running wheel which was monitored 24 h/d. We analyzed structural and functional development in vivo by echocardiography which revealed that neither the genotype nor the exercise caused any significant structural changes. Ejection fraction and fractional shortening were not influenced by the genotype itself, but exercise did cause a drop in both parameters after 8 weeks, which returned to normal after 16 weeks of training. The electrophysiological analysis revealed that the arrhythmogenic potential was slightly higher in heterozygous animals (50% vs 18% in wt littermates) and that an additional stressor (isoprenaline) did not lead to an increase of arrhythmogenic events pre run or after 8 weeks of running but the vulnerability was increased after 16 weeks. Exercise-induced alterations in Ca handling and contractility of isolated myocytes were mostly abolished in heterozygous animals. No fibrofatty replacements or rearrangement of gap junctions could be observed. Taken together we could show that light voluntary exercise can cause a transient aggravation of the mutation-induced phenotype which is abolished after long term exercise indicating a beneficial effect of long term light exercise.

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