scholarly journals Structural homo- and heterosynaptic plasticity in mature and adult newborn rat hippocampal granule cells

2018 ◽  
Vol 115 (20) ◽  
pp. E4670-E4679 ◽  
Author(s):  
Tassilo Jungenitz ◽  
Marcel Beining ◽  
Tijana Radic ◽  
Thomas Deller ◽  
Hermann Cuntz ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Granule Cells ◽  
Molecular Layer ◽  
Long Term Potentiation ◽  
Perforant Path ◽  
High Frequency Stimulation ◽  
Spatial Learning And Memory ◽  
Heterosynaptic Plasticity ◽  
Spine Plasticity

Adult newborn hippocampal granule cells (abGCs) contribute to spatial learning and memory. abGCs are thought to play a specific role in pattern separation, distinct from developmentally born mature GCs (mGCs). Here we examine at which exact cell age abGCs are synaptically integrated into the adult network and which forms of synaptic plasticity are expressed in abGCs and mGCs. We used virus-mediated labeling of abGCs and mGCs to analyze changes in spine morphology as an indicator of plasticity in rats in vivo. High-frequency stimulation of the medial perforant path induced long-term potentiation in the middle molecular layer (MML) and long-term depression in the nonstimulated outer molecular layer (OML). This stimulation protocol elicited NMDA receptor-dependent homosynaptic spine enlargement in the MML and heterosynaptic spine shrinkage in the inner molecular layer and OML. Both processes were concurrently present on individual dendritic trees of abGCs and mGCs. Spine shrinkage counteracted spine enlargement and thus could play a homeostatic role, normalizing synaptic weights. Structural homosynaptic spine plasticity had a clear onset, appearing in abGCs by 28 d postinjection (dpi), followed by heterosynaptic spine plasticity at 35 dpi, and at 77 dpi was equally as present in mature abGCs as in mGCs. From 35 dpi on, about 60% of abGCs and mGCs showed significant homo- and heterosynaptic plasticity on the single-cell level. This demonstration of structural homo- and heterosynaptic plasticity in abGCs and mGCs defines the time course of the appearance of synaptic plasticity and integration for abGCs.

Long-Term Depression in Identified Stellate Neurons of Juvenile Rat Entorhinal Cortex

2007 ◽  
Vol 97 (1) ◽  
pp. 727-737 ◽  
Author(s):  
Pan-Yue Deng ◽  
Saobo Lei
Keyword(s):  
Entorhinal Cortex ◽  
Molecular Mechanisms ◽  
Granule Cells ◽  
Long Term Potentiation ◽  
Cellular Mechanism ◽  
Perforant Path ◽  
High Frequency Stimulation ◽  
Cortical Input ◽  
Frequency Stimulation

The entorhinal cortex (EC) serves as a gateway to the hippocampus and plays a pivotal role in memory processing in the brain. Superficial layers of the EC convey the cortical input projections to the hippocampus, whereas deep layers of the EC relay hippocampal output projections back to the superficial layers of the EC or to other cortical regions. Whereas the EC expresses long-term potentiation (LTP) and depression (LTD), the underlying cellular and molecular mechanisms have not been determined. Because the axons of the stellate neurons in layer II of the EC form the perforant path that innervates the dentate gyrus granule cells of the hippocampus, we studied the mechanisms underlying the long-term plasticity in identified stellate neurons. Application of high-frequency stimulation (100 Hz for 1 s, repeated 3 times at an interval of 10 s) or forskolin (50 μM) failed to induce significant changes in synaptic strength, whereas application of pairing (presynaptic stimulation at 0.33 Hz paired with postsynaptic depolarization from −60 to −10 mV for 5 min) or low-frequency stimulation (LFS, 1 Hz for 15 min) paradigm-induced LTD. Pairing- or LFS-induced LTDs were N-methyl-d-aspartate receptor-dependent and occluded each other suggesting that they have the similar cellular mechanism. Pairing-induced LTD required the activity of calcineurin and involved AMPA receptor endocytosis that required the function of ubiquitin–proteasome system. Our study provides a cellular mechanism that might in part explain the role of the EC in memory.

scholarly journals Somatostatin Depresses Long-Term Potentiation and Ca2+ Signaling in Mouse Dentate Gyrus

2002 ◽  
Vol 88 (6) ◽  
pp. 3078-3086 ◽  
Author(s):  
Michael V. Baratta ◽  
Tyra Lamp ◽  
Melanie K. Tallent
Keyword(s):  
Dentate Gyrus ◽  
High Frequency ◽  
Granule Cells ◽  
Molecular Layer ◽  
Long Term Potentiation ◽  
Perforant Path ◽  
Functional Consequence ◽  
Term Potentiation ◽  
Synaptic Responses

The selective loss of somatostatin (SST)-containing interneurons from the hilus of the dentate gyrus is a hallmark of epileptic hippocampus. The functional consequence of this loss, including its contribution to postseizure hyperexcitability, remains unclear. We address this issue by characterizing the actions of SST in mouse dentate gyrus using electrophysiological techniques. Although the majority of dentate SST receptors are located in the outer molecular layer adjacent to lateral perforant path (LPP) synapses, we found no consistent action of SST on standard synaptic responses generated at these synapses. However, when SST was present during application of high-frequency trains that normally generate long-term potentiation (LTP), the induction of LTP was impaired. SST did not alter the maintenance of LTP when applied after its induction. To examine the mechanism by which SST inhibits LTP, we recorded from dentate granule cells and examined the actions of this neuropeptide on synaptic transmission and postsynaptic currents. Unlike findings in the CA1 hippocampus, we observed no postsynaptic actions on K+ currents. Instead, SST inhibited Ca2+/Ba2+ spikes evoked by depolarization. This inhibition was dependent on N-type Ca2+currents. Blocking these currents also blocked LTP, suggesting a mechanism through which SST may inhibit LTP. Our results indicate that SST reduction of dendritic Ca2+ through N-type Ca2+ channels may contribute to modulation of synaptic plasticity at LPP synapses. Therefore the loss of SST function postseizure could result in abnormal synaptic potentiation that contributes to epileptogenesis.

Effects of aging on axon terminals in the dentate molecular layer

1987 ◽  
Vol 45 ◽  
pp. 928-929
Author(s):  
K. Cullen-Dockstader ◽  
E. Fifkova
Keyword(s):  
Granule Cells ◽  
Molecular Layer ◽  
Age Groups ◽  
Long Term Potentiation ◽  
Male Rats ◽  
Perforant Path ◽  
Axon Terminals ◽  
Fischer 344 ◽  
Spatial Memory Deficit ◽  
Effects Of Aging

Normal aging results in a pronounced spatial memory deficit associated with a rapid decay of long-term potentiation at the synapses between the perforant path and spines in the medial and distal thirds of the dentate molecular layer (DML), suggesting the alteration of synaptic transmission in the dentate fascia. While the number of dentate granule cells remains unchanged, and there are no obvious pathological changes in these cells associated with increasing age, the density of their axospinous contacts has been shown to decrease. There are indications that the presynaptic element is affected by senescence before the postsynaptic element, yet little attention has been given to the fine structure of the remaining axon terminals. Therefore, we studied the axon terminals of the perforant path in the DML across three age groups.5 Male rats (Fischer 344) of each age group (3, 24 and 30 months), were perfused through the aorta.

scholarly journals Tau- but not Aß -pathology enhances NMDAR-dependent depotentiation in AD-mouse models

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Enrico Faldini ◽  
Tariq Ahmed ◽  
Luc Bueé ◽  
David Blum ◽  
Detlef Balschun
Keyword(s):  
Synaptic Plasticity ◽  
Transgenic Mice ◽  
Mouse Models ◽  
Long Term Potentiation ◽  
High Frequency Stimulation ◽  
Synaptic Loss ◽  
Ca1 Region ◽  
Term Potentiation ◽  
Frequency Stimulation

AbstractMany mouse models of Alzheimer’s disease (AD) exhibit impairments in hippocampal long-term-potentiation (LTP), seemingly corroborating the strong correlation between synaptic loss and cognitive decline reported in human studies. In other AD mouse models LTP is unaffected, but other defects in synaptic plasticity may still be present. We recently reported that THY-Tau22 transgenic mice, that overexpress human Tau protein carrying P301S and G272 V mutations and show normal LTP upon high-frequency-stimulation (HFS), develop severe changes in NMDAR mediated long-term-depression (LTD), the physiological counterpart of LTP. In the present study, we focused on putative effects of AD-related pathologies on depotentiation (DP), another form of synaptic plasticity. Using a novel protocol to induce DP in the CA1-region, we found in 11–15 months old male THY-Tau22 and APPPS1–21 transgenic mice that DP was not deteriorated by Aß pathology while significantly compromised by Tau pathology. Our findings advocate DP as a complementary form of synaptic plasticity that may help in elucidating synaptic pathomechanisms associated with different types of dementia.

Synaptic mechanisms underlying thalamic activation-induced plasticity in the rat auditory cortex

2014 ◽  
Vol 111 (9) ◽  
pp. 1746-1758 ◽  
Author(s):  
Zhi-ru Zhu ◽  
Fenglian Xu ◽  
Wei-gang Ji ◽  
Shuan-cheng Ren ◽  
Fang Chen ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Auditory Cortex ◽  
Frequency Tuning ◽  
Long Term Potentiation ◽  
High Frequency Stimulation ◽  
Excitatory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Medial Geniculate ◽  
Synaptic Mechanisms

Electrical stimulation of ventral division of medial geniculate body (MGBv) neurons evokes a shift of the frequency-tuning curves of auditory cortical (AC) neurons toward the best frequency (BF) of the stimulated MGBv neurons (frequency-specific plasticity). The shift of BF is induced by inhibition of responses at the BF of the recorded AC neuron, with coincident facilitation of responses at the BF of the stimulated MGBv neuron. However, the synaptic mechanisms are not yet understood. We hypothesize that activation of thalamocortical synaptic transmission and receptor function may contribute to MGBv stimulation-induced frequency-specific auditory plasticity and the shift of BF. To test this hypothesis, we measured changes in the excitatory postsynaptic currents in pyramidal neurons of layer III/IV in the auditory cortex following high-frequency stimulation (HFS) of the MGBv, using whole cell recordings in an auditory thalamocortical slice. Our data showed that in response to the HFS of the MGBv the excitatory postsynaptic currents of AC neurons showed long-term bidirectional synaptic plasticity and long-term potentiation and depression. Pharmacological studies indicated that the long-term synaptic plasticity was induced through the activation of different sets of N-methyl-d-aspartate-type glutamatergic receptors, γ-aminobutyric acid-type receptors, and type 5 metabotropic glutamate receptors. Our data further demonstrated that blocking of different receptors with specific antagonists significantly inhibited MGBv stimulation-induced long-term plasticity as well as the shift of BF. These data indicate that these receptors have an important role in mediating frequency-specific auditory cortical plasticity.

scholarly journals Dendritic spikes in hippocampal granule cells are necessary for long-term potentiation at the perforant path synapse

2018 ◽  
Author(s):  
Sooyun Kim ◽  
Yoonsub Kim ◽  
Suk-Ho Lee ◽  
Won-Kyung Ho
Keyword(s):  
Granule Cells ◽  
Memory Function ◽  
Brain Slices ◽  
Long Term Potentiation ◽  
Perforant Path ◽  
Term Potentiation ◽  
Dendritic Spikes ◽  
Voltage Attenuation ◽  
Synaptic Responses

AbstractLong-term potentiation (LTP) of synaptic responses is essential for hippocampal memory function. Perforant-path (PP) synapses on hippocampal granule cells (GCs) contribute to the formation of associative memories, which are considered the cellular correlates of memory engrams. However, the mechanisms of LTP at these synapses are not well understood. Due to sparse firing activity and the voltage attenuation in their dendrites, it remains unclear how associative LTP at distal synapses occurs. Here we show that NMDA receptor-dependent LTP can be induced at PP-GC synapses without backpropagating action potentials (bAPs) in acute rat brain slices. Dendritic recordings reveal substantial attenuation of bAPs as well as local dendritic Na + ‐spike generation during PP-GC input. Inhibition of Na+ ‐spikes impairs LTP suggesting that LTP at PP-GC synapse requires local Na + ‐spikes. Thus, dendritic spikes are essential for LTP induction at PP-GC synapse and may constitute a key cellular mechanism for memory formation in the dentate gyrus.

scholarly journals The Curious Anti-Pathology of the Wlds Mutation: Paradoxical Postsynaptic Spine Growth Accompanies Delayed Presynaptic Wallerian Degeneration

2021 ◽  
Vol 14 ◽  
Author(s):  
Oswald Steward ◽  
Jennifer M. Yonan ◽  
Paula M. Falk
Keyword(s):  
Wallerian Degeneration ◽  
Granule Cells ◽  
Long Term Potentiation ◽  
Perforant Path ◽  
Synaptic Membrane ◽  
Term Potentiation ◽  
Terminal Degeneration ◽  
Synapse Degeneration ◽  
Degenerating Axons

The Wlds mutation, which arose spontaneously in C57Bl/6 mice, remarkably delays the onset of Wallerian degeneration of axons. This remarkable phenotype has transformed our understanding of mechanisms contributing to survival vs. degeneration of mammalian axons after separation from their cell bodies. Although there are numerous studies of how the Wlds mutation affects axon degeneration, especially in the peripheral nervous system, less is known about how the mutation affects degeneration of CNS synapses. Here, using electron microscopy, we explore how the Wlds mutation affects synaptic terminal degeneration and withering and re-growth of dendritic spines on dentate granule cells following lesions of perforant path inputs from the entorhinal cortex. Our results reveal that substantial delays in the timing of synapse degeneration in Wlds mice are accompanied by paradoxical hypertrophy of spine heads with enlargement of post-synaptic membrane specializations (PSDs) and development of spinules. These increases in the complexity of spine morphology are similar to what is seen following induction of long-term potentiation (LTP). Robust and paradoxical spine growth suggests yet to be characterized signaling processes between amputated but non-degenerating axons and their postsynaptic targets.

scholarly journals The discovery of long-term potentiation

2003 ◽  
Vol 358 (1432) ◽  
pp. 617-620 ◽  
Author(s):  
Terje Lømo
Keyword(s):  
Granule Cells ◽  
Field Potential ◽  
Long Term Potentiation ◽  
Perforant Path ◽  
Term Potentiation ◽  
Basic Reference ◽  
Potential Recording ◽  
Independent Work ◽  
Field Potential Recording

This paper describes circumstances around the discovery of long-term potentiation (LTP). In 1966, I had just begun independent work for the degree of Dr medicinae (PhD) in Per Andersen's laboratory in Oslo after an eighteen-month apprenticeship with him. Studying the effects of activating the perforant path to dentate granule cells in the hippocampus of anaesthetized rabbits, I observed that brief trains of stimuli resulted in increased efficiency of transmission at the perforant path-granule cell synapses that could last for hours. In 1968, Tim Bliss came to Per Andersen's laboratory to learn about the hippocampus and field potential recording for studies of possible memory mechanisms. The two of us then followed up my preliminary results from 1966 and did the experiments that resulted in a paper that is now properly considered to be the basic reference for the discovery of LTP.

scholarly journals Dendritic spikes in hippocampal granule cells are necessary for long-term potentiation at the perforant path synapse

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Sooyun Kim ◽  
Yoonsub Kim ◽  
Suk-Ho Lee ◽  
Won-Kyung Ho
Keyword(s):  
Granule Cells ◽  
Memory Function ◽  
Brain Slices ◽  
Long Term Potentiation ◽  
Perforant Path ◽  
Term Potentiation ◽  
Dendritic Spikes ◽  
Voltage Attenuation ◽  
Synaptic Responses

Long-term potentiation (LTP) of synaptic responses is essential for hippocampal memory function. Perforant-path (PP) synapses on hippocampal granule cells (GCs) contribute to the formation of associative memories, which are considered the cellular correlates of memory engrams. However, the mechanisms of LTP at these synapses are not well understood. Due to sparse firing activity and the voltage attenuation in their dendrites, it remains unclear how associative LTP at distal synapses occurs. Here, we show that NMDA receptor-dependent LTP can be induced at PP-GC synapses without backpropagating action potentials (bAPs) in acute rat brain slices. Dendritic recordings reveal substantial attenuation of bAPs as well as local dendritic Na+ spike generation during PP-GC input. Inhibition of dendritic Na+ spikes impairs LTP induction at PP-GC synapse. These data suggest that dendritic spikes may constitute a key cellular mechanism for memory formation in the dentate gyrus.

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