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 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.

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.

scholarly journals Sniff-Like Patterned Input Results in Long-Term Plasticity at the Rat Olfactory Bulb Mitral and Tufted Cell to Granule Cell Synapse

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Mahua Chatterjee ◽  
Fernando Perez de los Cobos Pallares ◽  
Alex Loebel ◽  
Michael Lukas ◽  
Veronica Egger
Keyword(s):  
Olfactory Bulb ◽  
Granule Cells ◽  
Brain Slices ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Term Potentiation ◽  
Presynaptic Release ◽  
Extra Activity ◽  
Hippocampal Theta

During odor sensing the activity of principal neurons of the mammalian olfactory bulb, the mitral and tufted cells (MTCs), occurs in repetitive bursts that are synchronized to respiration, reminiscent of hippocampal theta-gamma coupling. Axonless granule cells (GCs) mediate self- and lateral inhibitory interactions between the excitatory MTCs via reciprocal dendrodendritic synapses. We have explored long-term plasticity at this synapse by using a theta burst stimulation (TBS) protocol and variations thereof. GCs were excited via glomerular stimulation in acute brain slices. We find that TBS induces exclusively long-term depression in the majority of experiments, whereas single bursts (“single-sniff paradigm”) can elicit both long-term potentiation and depression. Statistical analysis predicts that the mechanism underlying this bidirectional plasticity involves the proportional addition or removal of presynaptic release sites. Gamma stimulation with the same number of APs as in TBS was less efficient in inducing plasticity. Both TBS- and “single-sniff paradigm”-induced plasticity depend on NMDA receptor activation. Since the onset of plasticity is very rapid and requires little extra activity, we propose that these forms of plasticity might play a role already during an ongoing search for odor sources. Our results imply that components of both short-term and long-term olfactory memory may be encoded at this synapse.

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.

Mechanisms underlying induction of long-term potentiation in rat medial and lateral perforant paths in vitro

1993 ◽  
Vol 69 (4) ◽  
pp. 1150-1159 ◽  
Author(s):  
A. Colino ◽  
R. C. Malenka
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Intracellular Calcium ◽  
Granule Cells ◽  
Long Term Potentiation ◽  
Nmda Receptor Antagonist ◽  
Perforant Path ◽  
Term Potentiation

1. The mechanisms underlying the induction of long-term potentiation (LTP) in the medial and lateral perforant paths were studied by recording excitatory postsynaptic potentials (EPSPs) from rat dentate granule cells in vitro using extracellular and whole-cell recording techniques. 2. Paired stimuli (interstimulus interval, 50-1,000 ms) resulted in facilitation of the lateral and depression of the medial perforant path-evoked EPSPs, respectively. This physiological difference was used to isolate responses evoked by stimulation of a single path. 3. Tetanic stimulation induced LTP in both pathways, although the magnitude of LTP in the lateral perforant path was significantly less than that in the medial perforant path. Both forms of LTP were blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovaleric acid (D-APV). 4. Buffering intracellular calcium by loading granule cells with the calcium chelator bis (O-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid prevented LTP in both pathways. 5. Pairing of low-frequency (0.25 Hz) afferent stimulation with postsynaptic depolarization induced LTP in the medial but not the lateral perforant path. However, pairing of higher-frequency stimulation (1-4 Hz) with postsynaptic depolarization did potentiate the lateral perforant path-evoked EPSP in some cells. 6. Both the medial and lateral perforant path-evoked EPSPs had two components; a fast component blocked by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione and a slower, voltage-dependent component blocked by D-APV. 7. The results indicate that the induction of LTP in both the medial and lateral perforant paths requires activation of postsynaptic NMDA receptors and a rise in intracellular calcium.(ABSTRACT TRUNCATED AT 250 WORDS)

In Vivo Recordings of Long-Term Potentiation and Long-Term Depression in the Dentate Gyrus of the Neonatal Rat

2004 ◽  
Vol 91 (2) ◽  
pp. 613-622 ◽  
Author(s):  
Michael P. O'Boyle ◽  
Viet Do ◽  
Brian E. Derrick ◽  
Brenda J. Claiborne
Keyword(s):  
Dentate Gyrus ◽  
Granule Cells ◽  
Long Term Potentiation ◽  
Neonatal Rat ◽  
Perforant Path ◽  
Long Term Depression ◽  
Term Potentiation ◽  
Old Rats

Previous in vitro studies demonstrated that long-term potentiation (LTP) could be elicited at medial perforant path (MPP) synapses onto hippocampal granule cells in slices from 7-day-old rats. In contrast, in vivo studies suggested that LTP at perforant path synapses could not be induced until at least days 9 or 10 and then in only a small percentage of animals. Because several characteristics of the oldest granule cells are adult-like on day 7, we re-examined the possibility of eliciting LTP in 7-day-old rats in vivo. We also recorded from 8- and 9-day-old rats to further elucidate the occurrence and magnitude of LTP in neonates. With halothane anesthesia, all animals in each age group exhibited synaptic plasticity of the excitatory postsynaptic potential following high-frequency stimulation of the MPP. In 7-day-old rats, LTP was elicited in 40% of the animals and had an average magnitude of 143%. Long-term depression (LTD) alone (magnitude of 84%) was induced in 40% of the animals, while short-term potentiation (STP) alone (magnitude of 123%) was induced in 10%. STP followed by LTD was elicited in the remaining 10%. Data were similar for all ages combined. In addition, the N-methyl-d-aspartate (NMDA) antagonist ( R,S)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) blocked the occurrence of LTP at each age and doubled the percentage of animals expressing LTD alone for all ages combined. These results demonstrate that tetanic stimulation can elicit LTP or LTD at MPP synapses in 7-day-old rats, supporting our premise that at least a portion of the dentate gyrus is functional at this early age.

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