The Cerebellar Mossy Fiber Synapse as a Model for High-Frequency Transmission in the Mammalian CNS

2016 ◽  
Vol 39 (11) ◽  
pp. 722-737 ◽  
Author(s):  
Igor Delvendahl ◽  
Stefan Hallermann
eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
E Anne Martin ◽  
Shruti Muralidhar ◽  
Zhirong Wang ◽  
Diégo Cordero Cervantes ◽  
Raunak Basu ◽  
...  

Synaptic target specificity, whereby neurons make distinct types of synapses with different target cells, is critical for brain function, yet the mechanisms driving it are poorly understood. In this study, we demonstrate Kirrel3 regulates target-specific synapse formation at hippocampal mossy fiber (MF) synapses, which connect dentate granule (DG) neurons to both CA3 and GABAergic neurons. Here, we show Kirrel3 is required for formation of MF filopodia; the structures that give rise to DG-GABA synapses and that regulate feed-forward inhibition of CA3 neurons. Consequently, loss of Kirrel3 robustly increases CA3 neuron activity in developing mice. Alterations in the Kirrel3 gene are repeatedly associated with intellectual disabilities, but the role of Kirrel3 at synapses remained largely unknown. Our findings demonstrate that subtle synaptic changes during development impact circuit function and provide the first insight toward understanding the cellular basis of Kirrel3-dependent neurodevelopmental disorders.


Glia ◽  
2019 ◽  
Vol 68 (5) ◽  
pp. 947-962 ◽  
Author(s):  
Amira A. H. Ali ◽  
Beryl Schwarz‐Herzke ◽  
Astrid Rollenhagen ◽  
Max Anstötz ◽  
Martin Holub ◽  
...  

1998 ◽  
Vol 79 (4) ◽  
pp. 2181-2190 ◽  
Author(s):  
Ajay Kapur ◽  
Mark F. Yeckel ◽  
Richard Gray ◽  
Daniel Johnston

Kapur, Ajay, Mark F. Yeckel, Richard Gray, and Daniel Johnston. L-type calcium channels are required for one form of hippocampal mossy fiber LTP. J. Neurophysiol. 79: 2181–2190, 1998. The requirement of postsynaptic calcium influx via L-type channels for the induction of long-term potentiation (LTP) of mossy fiber input to CA3 pyramidal neurons was tested for two different patterns of stimulation. Two types of LTP-inducing stimuli were used based on the suggestion that one of them, brief high-frequency stimulation (B-HFS), induces LTP postsynaptically, whereas the other pattern, long high-frequency stimulation (L-HFS), induces mossy fiber LTP presynaptically. To test whether or not calcium influx into CA3 pyramidal neurons is necessary for LTP induced by either pattern of stimulation, nimodipine, a L-type calcium channel antagonist, was added during stimulation. In these experiments nimodipine blocked the induction of mossy fiber LTP when B-HFS was given [34 ± 5% (mean ± SE) increase in control versus 7 ± 4% in nimodipine, P < 0.003]; in contrast, nimodipine did not block the induction of LTP with L-HFS (107 ± 10% in control vs. 80 ± 9% in nimodipine, P > 0.05). Administration of nimodipine after the induction of LTP had no effect on the expression of LTP. In addition, B- and L-HFS delivered directly to commissural/associational fibers in stratum radiatum failed to induce a N-methyl-d-aspartate-independent form of LTP, obviating the possibility that the presumed mossy fiber LTP resulted from potentiation of other synapses. Nimodipine had no effect on calcium transients recorded from mossy fiber presynaptic terminals evoked with the B-HFS paradigm but reduced postsynaptic calcium transients. Our results support the hypothesis that induction of mossy fiber LTP by B-HFS is mediated postsynaptically and requires entry of calcium through L-type channels into CA3 neurons.


2013 ◽  
Vol 33 (2) ◽  
pp. 507-522 ◽  
Author(s):  
S. A. Wilke ◽  
J. K. Antonios ◽  
E. A. Bushong ◽  
A. Badkoobehi ◽  
E. Malek ◽  
...  

2019 ◽  
Vol 121 (2) ◽  
pp. 609-619 ◽  
Author(s):  
Enhui Pan ◽  
Zirun Zhao ◽  
James O. McNamara

Hippocampal mossy fiber axons simultaneously activate CA3 pyramidal cells and stratum lucidum interneurons (SLINs), the latter providing feedforward inhibition to control CA3 pyramidal cell excitability. Filopodial extensions of giant boutons of mossy fibers provide excitatory synaptic input to the SLIN. These filopodia undergo extraordinary structural plasticity causally linked to execution of memory tasks, leading us to seek the mechanisms by which activity regulates these synapses. High-frequency stimulation of the mossy fibers induces long-term depression (LTD) of their calcium-permeable AMPA receptor synapses with SLINs; previous work localized the site of induction to be postsynaptic and the site of expression to be presynaptic. Yet, the underlying signaling events and the identity of the retrograde signal are incompletely understood. We used whole cell recordings of SLINs in hippocampal slices from wild-type and mutant mice to explore the mechanisms. Genetic and pharmacologic perturbations revealed a requirement for both the receptor tyrosine kinase TrkB and its agonist, brain-derived neurotrophic factor (BDNF), for induction of LTD. Inclusion of inhibitors of Trk receptor kinase and PLC in the patch pipette prevented LTD. Endocannabinoid receptor antagonists and genetic deletion of the CB1 receptor prevented LTD. We propose a model whereby release of BDNF from mossy fiber filopodia activates TrkB and PLCγ1 signaling postsynaptically within SLINs, triggering synthesis and release of an endocannabinoid that serves as a retrograde signal, culminating in reduced glutamate release. Insights into the signaling pathways by which activity modifies function of these synapses will facilitate an understanding of their contribution to the local circuit and behavioral consequences of hippocampal granule cell activity. NEW & NOTEWORTHY We investigated signaling mechanisms underlying plasticity of the hippocampal mossy fiber filopodial synapse with interneurons in stratum lucidum. High-frequency stimulation of the mossy fibers induces long-term depression of this synapse. Our findings are consistent with a model in which brain-derived neurotrophic factor released from filopodia activates TrkB of a stratum lucidum interneuron; the ensuing activation of PLCγ1 induces synthesis of an endocannabinoid, which provides a retrograde signal leading to reduced release of glutamate presynaptically.


iScience ◽  
2020 ◽  
Vol 23 (4) ◽  
pp. 101025
Author(s):  
Katsunori Kobayashi ◽  
Yasunori Mikahara ◽  
Yuka Murata ◽  
Daiki Morita ◽  
Sumire Matsuura ◽  
...  

2008 ◽  
Vol 105 (33) ◽  
pp. 11998-12003 ◽  
Author(s):  
H. Shimizu ◽  
M. Fukaya ◽  
M. Yamasaki ◽  
M. Watanabe ◽  
T. Manabe ◽  
...  

PLoS ONE ◽  
2011 ◽  
Vol 6 (3) ◽  
pp. e18113 ◽  
Author(s):  
Katsunori Kobayashi ◽  
Satomi Umeda-Yano ◽  
Hidenaga Yamamori ◽  
Masatoshi Takeda ◽  
Hidenori Suzuki ◽  
...  

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