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 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 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 Heterosynaptic NMDA Receptor Plasticity in Hippocampal Dentate Granule Cells

2022 ◽  
Author(s):  
Alma Rodenas-Ruano ◽  
Kaoutsar Nasrallah ◽  
Stefano Lutzu ◽  
Maryann Castillo ◽  
Pablo E. Castillo
Keyword(s):  
Dentate Gyrus ◽  
Entorhinal Cortex ◽  
Information Transfer ◽  
Granule Cells ◽  
Hippocampal Slices ◽  
Dentate Granule Cells ◽  
Hippocampus Proper ◽  
Receptor Plasticity ◽  
Activity Dependent

The dentate gyrus is a key relay station that controls information transfer from the entorhinal cortex to the hippocampus proper. This process heavily relies on dendritic integration by dentate granule cells (GCs) of excitatory synaptic inputs from medial and lateral entorhinal cortex via medial and lateral perforant paths (MPP and LPP, respectively). N-methyl-D-aspartate receptors (NMDARs) can contribute significantly to the integrative properties of neurons. While early studies reported that excitatory inputs from entorhinal cortex onto GCs can undergo activity-dependent long-term plasticity of NMDAR-mediated transmission, the input-specificity of this plasticity along the dendritic axis remains unknown. Here, we examined the NMDAR plasticity rules at MPP-GC and LPP-GC synapses using physiologically relevant patterns of stimulation in acute rat hippocampal slices. We found that MPP-GC, but not LPP-GC synapses, expressed homosynaptic NMDAR-LTP. In addition, induction of NMDAR-LTP at MPP-GC synapses heterosynaptically potentiated distal LPP-GC NMDAR plasticity. The same stimulation protocol induced homosynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-LTP at MPP-GC but heterosynaptic AMPAR-LTD at distal LPP synapses, demonstrating that NMDAR and AMPAR are governed by different plasticity rules. Remarkably, heterosynaptic but not homosynaptic NMDAR-LTP required Ca2+ release from intracellular, ryanodine-dependent Ca2+ stores. Lastly, the induction and maintenance of both homo- and heterosynaptic NMDAR-LTP were blocked by GluN2D antagonism, suggesting the recruitment of GluN2D-containing receptors to the synapse. Our findings uncover a mechanism by which distinct inputs to the dentate gyrus may interact functionally and contribute to hippocampal-dependent memory formation.

scholarly journals Activity-Dependent Reconnection of Adult-Born Dentate Granule Cells in a Mouse Model of Frontotemporal Dementia

2019 ◽  
Vol 39 (29) ◽  
pp. 5794-5815 ◽  
Author(s):  
Julia Terreros-Roncal ◽  
Miguel Flor-García ◽  
Elena P. Moreno-Jiménez ◽  
Noemí Pallas-Bazarra ◽  
Alberto Rábano ◽  
...  
Keyword(s):  
Mouse Model ◽  
Frontotemporal Dementia ◽  
Granule Cells ◽  
Dentate Granule Cells ◽  
Activity Dependent

Neurotrophins and their receptors: roles in plasticity, neurodegeneration and neuroprotection

2007 ◽  
Vol 35 (2) ◽  
pp. 424-427 ◽  
Author(s):  
A. Hennigan ◽  
R.M. O'Callaghan ◽  
Á.M. Kelly
Keyword(s):  
Tyrosine Kinases ◽  
Current Knowledge ◽  
Adult Brain ◽  
Neurotrophin Receptor ◽  
Receptor Subtypes ◽  
P75 Neurotrophin Receptor ◽  
Receptor Kinase ◽  
Dual Roles ◽  
Exercise Induced ◽  
Activity Dependent

It is beyond doubt that the neurotrophin family of proteins plays key roles in determining the fate of the neuron, not only during embryonic development, but also in the adult brain. Neurotrophins such as NGF (nerve growth factor) and BDNF (brain-derived neurotrophic factor) can play dual roles: first, in neuronal survival and death, and, secondly, in activity-dependent plasticity. The neurotrophins manifest their effects by binding to two discrete receptor subtypes: the Trk (tropomyosin receptor kinase) family of RTKs (receptor tyrosine kinases) and the p75NTR (p75 neurotrophin receptor). The differential activation of these receptors by the mature neurotrophins and their precursors, the proneurotrophins, renders analysis of the biological functions of these receptors in the adult brain highly complex. Here, we briefly give a broad review of current knowledge of the roles of neurotrophins in the adult brain, including expression of hippocampal plasticity, neurodegeneration and exercise-induced neuroprotection.

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.

Sign in / Sign up

Export Citation Format

Share Document