scholarly journals Loss of protohaem IX farnesyltransferase in mature dentate granule cells impairs short-term facilitation at mossy fibre to CA3 pyramidal cell synapses

2017 ◽  
Vol 595 (6) ◽  
pp. 2147-2160 ◽  
Author(s):  
Sam A. Booker ◽  
Graham R. Campbell ◽  
Karolina S. Mysiak ◽  
Peter J. Brophy ◽  
Peter C. Kind ◽  
...  
Keyword(s):  
Pyramidal Cell ◽  
Granule Cells ◽  
Mossy Fibre ◽  
Short Term ◽  
Dentate Granule Cells

PKA and PKC Enhance Excitatory Synaptic Transmission in Human Dentate Gyrus

2003 ◽  
Vol 89 (5) ◽  
pp. 2482-2488 ◽  
Author(s):  
Huan-Xin Chen ◽  
Steven N. Roper
Keyword(s):  
Protein Kinase ◽  
Synaptic Transmission ◽  
Dentate Gyrus ◽  
Phorbol Ester ◽  
Granule Cells ◽  
Excitatory Synaptic Transmission ◽  
Perforant Path ◽  
Short Term ◽  
Dentate Granule Cells ◽  
Presynaptic Mechanisms

cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) are two major modulators of synaptic transmission in the CNS but little is known about how they affect synaptic transmission in the human CNS. In this study, we used forskolin, a PKA activator, and phorbol ester, a PKC activator, to examine the effects of these kinases on synaptic transmission in granule cells of the dentate gyrus in human hippocampal slices using whole-cell recording methods. We found that both forskolin and phorbol ester increased the frequency of spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs) but left the amplitude unaffected. Inactive forskolin and phorbol ester had no effect on sEPSCs in human dentate granule cells. Prior application of forskolin occluded the effects of phorbol ester on mEPSC frequency. Tetanic stimulation applied to the perforant path induced short-term depression in dentate gyrus granule cells. Both forskolin and phorbol ester significantly enhanced this short-term depression. Taken together, these results demonstrate that PKA and PKC are involved in up-regulation of excitatory synaptic transmission in human dentate granule cells, primarily by presynaptic mechanisms. In addition, the occlusion experiments suggest that the two kinases may share a common signal pathway.

scholarly journals Retrograde suppression of post-tetanic potentiation at the mossy fiber-CA3 pyramidal cell synapse

2020 ◽  
Author(s):  
Sachin Makani ◽  
Stefano Lutzu ◽  
Pablo J. Lituma ◽  
David L. Hunt ◽  
Pablo E. Castillo
Keyword(s):  
Metabotropic Glutamate Receptors ◽  
Granule Cells ◽  
Mossy Fiber ◽  
Hippocampal Slices ◽  
Dependent Manner ◽  
Short Term ◽  
Short Term Plasticity ◽  
Dentate Granule Cells ◽  
Post Tetanic Potentiation ◽  
Frequency Facilitation

ABSTRACTIn the hippocampus, the excitatory synapse between dentate granule cell axons – or mossy fibers (MF) – and CA3 pyramidal cells (MF-CA3) expresses robust forms of short-term plasticity, such as frequency facilitation and post-tetanic potentiation (PTP). These forms of plasticity are due to increases in neurotransmitter release, and can be engaged when dentate granule cells fire in bursts (e.g. during exploratory behaviors) and bring CA3 pyramidal neurons above threshold. While frequency facilitation at this synapse is limited by endogenous activation of presynaptic metabotropic glutamate receptors, whether MF-PTP can be regulated in an activity-dependent manner is unknown. Here, using physiologically relevant patterns of mossy fiber stimulation in acute mouse hippocampal slices, we found that disrupting postsynaptic Ca2+ dynamics increases MF-PTP, strongly suggesting a form of Ca2+-dependent retrograde suppression of this form of plasticity. PTP suppression requires a few seconds of MF bursting activity and Ca2+ release from internal stores. Our findings raise the possibility that the powerful MF-CA3 synapse can negatively regulate its own strength not only during PTP-inducing activity typical of normal exploratory behaviors, but also during epileptic activity.SIGNIFICANCE STATEMENTThe powerful mossy fiber-CA3 synapse exhibits strong forms of plasticity that are engaged during location-specific exploration, when dentate granule cells fire in bursts. While this synapse is well-known for its presynaptically-expressed LTP and LTD, much less is known about the robust changes that occur on a shorter time scale. How such short-term plasticity is regulated, in particular, remains poorly understood. Unexpectedly, an in vivo-like pattern of presynaptic activity induced robust post-tetanic potentiation (PTP) only when the postsynaptic cell was loaded with a high concentration of Ca2+ buffer, indicating a form of Ca2+–dependent retrograde suppression of PTP. Such suppression may have profound implications for how environmental cues are encoded into neural assemblies, and for limiting network hyperexcitability during seizures.

scholarly journals Early detonation by sprouted mossy fibers enables aberrant dentate network activity

2018 ◽  
Author(s):  
William D. Hendricks ◽  
Gary L. Westbrook ◽  
Eric Schnell
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
High Probability ◽  
Granule Cells ◽  
Mossy Fiber ◽  
Glutamate Release ◽  
Mossy Fibers ◽  
Network Activity ◽  
Short Term ◽  
Dentate Granule Cells

AbstractIn temporal lobe epilepsy, sprouting of hippocampal mossy fiber axons onto dentate granule cell dendrites creates a recurrent excitatory network. However, unlike mossy fibers projecting to CA3, sprouted mossy fiber synapses depress upon repetitive activation. Thus, despite their proximal location, large presynaptic terminals, and ability to excite target neurons, the impact of sprouted mossy fiber synapses on hippocampal hyperexcitability is unclear. We find that despite their short-term depression, single episodes of sprouted mossy fiber activation in hippocampal slices initiated bursts of recurrent polysynaptic excitation. Consistent with a contribution to network hyperexcitability, optogenetic activation of sprouted mossy fibers reliably triggered action potential firing in postsynaptic dentate granule cells after single light pulses. This pattern resulted in a shift in network recruitment dynamics to an “early detonation” mode and an increased probability of release compared to mossy fiber synapses in CA3. A lack of tonic adenosine-mediated inhibition contributed to the higher probability of glutamate release thus facilitating reverberant circuit activity.Significance StatementSprouted mossy fibers are one of the hallmark histopathological findings in temporal lobe epilepsy. These fibers form recurrent excitatory synapses onto other dentate granule cells that display profound short-term depression. Here, however, we show that although these sprouted mossy fibers weaken substantially during repetitive activation, their initial high probability of glutamate release can activate reverberant network activity. Furthermore, we find that a lack of tonic adenosine inhibition enables this high probability of release and, consequently, recurrent network activity.

scholarly journals Increased Expression of Axogenesis-Related Genes and Mossy Fibre Length in Dentate Granule Cells from Adult HuD Overexpressor Mice

ASN NEURO ◽  
2011 ◽  
Vol 3 (5) ◽  
pp. AN20110015 ◽  
Author(s):  
Nora I Perrone-Bizzozero ◽  
Daniel C Tanner ◽  
Joanna Mounce ◽  
Federico Bolognani
Keyword(s):  
Granule Cells ◽  
Fibre Length ◽  
Mossy Fibre ◽  
Dentate Granule Cells

scholarly journals Amyloid β-Mediated Zn2+ Influx into Dentate Granule Cells Transiently Induces a Short-Term Cognitive Deficit

PLoS ONE ◽  
2014 ◽  
Vol 9 (12) ◽  
pp. e115923 ◽  
Author(s):  
Atsushi Takeda ◽  
Masatoshi Nakamura ◽  
Hiroaki Fujii ◽  
Chihiro Uematsu ◽  
Tatsuya Minamino ◽  
...  
Keyword(s):  
Cognitive Deficit ◽  
Granule Cells ◽  
Amyloid Β ◽  
Short Term ◽  
Dentate Granule Cells
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