Electrical Stimuli Patterned After the Theta-Rhythm Induce Multiple Forms of LTP

2001 ◽  
Vol 86 (3) ◽  
pp. 1289-1296 ◽  
Author(s):  
S. L. Morgan ◽  
T. J. Teyler
Keyword(s):  
Calcium Influx ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
High Frequency Stimulation ◽  
Natural Activity ◽  
Term Potentiation ◽  
Voltage Dependent ◽  
Acceptable Model ◽  
Voltage Dependent Calcium Channels ◽  
Frequency Stimulation

The induction of long-term potentiation (LTP) by high-frequency stimulation is considered an acceptable model for the study of learning and memory. In area CA1 calcium influx through N-methyl-d-aspartate receptors (NMDARs; nmdaLTP) and/or L-type voltage-dependent calcium channels (vdccLTP) results in distinct forms of LTP. In the light of significant accumulation of knowledge about patterns of naturally occurring activity in the intact animal, we examined whether the application of stimuli patterned after natural activity induced nmdaLTP and/or vdccLTP. In rat hippocampal slices we examined LTP induced by three types of patterned stimulation short (S-TBS), long (L-TBS), and high-intensity long theta-patterned stimulation (HL-TBS). The patterns of stimulation were applied in control, nifedipine (blocks vdccLTP),d,l-2-amino-5-phosphonovaleric acid (APV; blocks nmdaLTP), or APV and nifedipine containing media. We found that S-TBS resulted in LTP that was completely attenuated in the presence of APV but was unaffected by nifedipine. Thus S-TBS results in the selective induction of nmdaLTP. L-TBS resulted in LTP that was completely blocked by APV and only partially blocked by nifedipine. Therefore L-TBS results in a compoundLTP consisting of both nmdaLTP and vdccLTP components. In the presence of APV, HL-TBS resulted in vdccLTP, and when APV and nifedipine were both present, LTP was completely blocked. Thus HL-TBS results in a vdccLTP in isolation when APV is present. We also examined saturation of S-TBS–induced LTP (nmdaLTP) by applying S-TBS at short intervals. When nifedipine was present, multiple S-TBS trains resulted in a substantially smaller final LTP as compared with controls. We conclude that multiple bursts of S-TBS eventually summate to result in compoundLTP. Stimuli patterned after innate rhythms in the hippocampus effectively induce nmdaLTP (S-TBS), compoundLTP (L-TBS), or vdccLTP (HL-TBS).

Distinct LTP induction mechanisms: contribution of NMDA receptors and voltage-dependent calcium channels

1995 ◽  
Vol 73 (1) ◽  
pp. 270-279 ◽  
Author(s):  
K. M. Huber ◽  
M. D. Mauk ◽  
P. T. Kelly
Keyword(s):  
Nmda Receptor ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Nmda Receptor Antagonist ◽  
K Channel ◽  
Combined Application ◽  
Term Potentiation ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels

1. Our results indicate that there are two distinct components of long-term potentiation (LTP) induced by the K+ channel blocker tetraethylammonium chloride (TEA) at synapses of hippocampal CA1 pyramidal neurons. Preincubation of hippocampal slices in the N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2-amino-5 phosphonovalerate (D,L-APV, 50 microM), reduced the magnitude of TEA LTP. In addition, the L-type voltage-dependent Ca2+ channel (VDCC) antagonist nifedipine (10 microM) attenuated TEA LTP. Only the combined application of D,L-APV plus nifedipine blocked the induction of TEA LTP. 2. Occlusion experiments demonstrated that saturation of VDCC-dependent TEA LTP did not reduce or occlude NMDA-receptor-dependent TEA LTP. These results indicate that the mechanisms underlying VDCC and NMDA receptor components of TEA LTP are different and do not share a common saturable mechanism. 3. TEA LTP was strictly dependent on NMDA receptor activity in slices with CA3-CA1 connections severed (isolated CA1 slices). In contrast to results obtained in slices with intact CA3-CA1 connections, the NMDA receptor antagonists APV (50 microM) or MK-801 dizocilpine (10 microM) completely blocked TEA LTP in isolated CA1. Consistent with this observation, the properties of TEA LTP in isolated CA1 were very similar to other types of NMDA-receptor-dependent plasticity such as tetanus-induced LTP; TEA LTP required presynaptic stimulation, displayed pathway specificity, and was occluded by tetanus-induced LTP.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Long-Term Recording of LTP in Cultured Hippocampal Slices

2002 ◽  
Vol 9 (4) ◽  
pp. 249-254 ◽  
Author(s):  
Ken Shimono ◽  
Michel Baudry ◽  
Lam Ho ◽  
Makoto Taketani ◽  
Gary Lynch
Keyword(s):  
Nmda Receptor ◽  
High Frequency ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
High Frequency Stimulation ◽  
Electrode Arrays ◽  
Chronic Recording ◽  
Term Potentiation ◽  
Frequency Stimulation

Long-term potentiation (LTP) was elicited by high frequency stimulation in hippocampal slices cultured on multi-electrode arrays. LTP lasting more than 1 h was recorded in 75% of slices, and a significant number of slices exhibited a non-decaying LTP that lasted more than 48 h. LTP induction was completely and reversibly blocked by an antagonist of the NMDA receptor, APV. Our results suggest the possibility of using chronic recording in hippocampal slices cultured on multi-electrode arrays to study the mechanisms underlying LTP maintenance and stabilization.

scholarly journals Different Calcium Sources Are Narrowly Tuned to the Induction of Different Forms of LTP

2002 ◽  
Vol 88 (1) ◽  
pp. 249-255 ◽  
Author(s):  
Clarke R. Raymond ◽  
Stephen J. Redman
Keyword(s):  
Calcium Influx ◽  
Ryanodine Receptors ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Ip3 Receptors ◽  
Term Potentiation ◽  
Voltage Dependent ◽  
Calcium Sources

The essential role of calcium in the induction of long-term potentiation (LTP) has been well established. In particular, calcium influx via the N-methyl-d-aspartate (NMDA) receptor (NMDAR) is important for LTP induction in many pathways. However, the specific roles of other calcium sources in hippocampal LTP are less clear. The aim of the present study was to determine the appropriate conditions and extent to which non-NMDAR Ca2+ sources contribute to the induction of different forms of LTP in area CA1 of hippocampal slices. Increasing numbers of theta-burst trains (1, 4, and 8 TBS) induced LTP of increasing magnitude and persistence. Inhibition of ryanodine receptors caused inhibition of weak LTP induced by 1 TBS, but had no effect on more robust forms of LTP. Inhibition of IP3 receptors inhibited moderate LTP induced by 4 TBS, but had no effect when 1 TBS or 8 TBS were used. Inhibition of L-type voltage–dependent Ca2+ channels inhibited strong LTP induced by 8 TBS, but had no effect on weaker forms of LTP. These results show that different Ca2+ sources have different thresholds for activation by TBS trains. Furthermore, each Ca2+ source appears to be tuned to the induction of a different form of LTP. Such tuning could reflect an important link between different LTP induction and maintenance mechanisms.

scholarly journals Imaging spatio-temporal patterns of long-term potentiation in mouse hippocampus

2003 ◽  
Vol 358 (1432) ◽  
pp. 689-693 ◽  
Author(s):  
Toshiyuki Hosokawa ◽  
Masaki Ohta ◽  
Takeshi Saito ◽  
Alan Fine
Keyword(s):  
Hippocampal Slices ◽  
Temporal Patterns ◽  
Long Term Potentiation ◽  
Optical Recording ◽  
Stratum Radiatum ◽  
High Frequency Stimulation ◽  
Optical Signals ◽  
Term Potentiation ◽  
Spatio Temporal

Spatio-temporal patterns of neuronal activity before and after the induction of long-term potentiation in mouse hippocampal slices were studied using a real-time high-resolution optical recording system. After staining the slices with voltage-sensitive dye, transmitted light images and extracellular field potentials were recorded in response to stimuli applied to CA1 stratum radiatum. Optical and electrical signals in response to single test pulses were enhanced for at least 30 minutes after brief high-frequency stimulation at the same site. In two-pathway experiments, potentiation was restricted to the tetanized pathway. The optical signals demonstrated that both the amplitude and area of the synaptic response were increased, in patterns not predictable from the initial, pretetanus, pattern of activation. Optical signals will be useful for investigating spatio-temporal patterns of synaptic enhancement underlying information storage in the brain.

scholarly journals Interactions between calmodulin and neurogranin govern the dynamics of CaMKII as a leaky integrator

2019 ◽  
Author(s):  
Mariam Ordyan ◽  
Tom Bartol ◽  
Mary Kennedy ◽  
Padmini Rangamani ◽  
Terrence Sejnowski
Keyword(s):  
Long Term Potentiation ◽  
Time Averaging ◽  
Calcium Signals ◽  
Term Potentiation ◽  
High Calcium ◽  
Leaky Integrator ◽  
Voltage Dependent ◽  
High Calcium Concentration ◽  
Voltage Dependent Calcium Channels

AbstractCalmodulin-dependent kinase II (CaMKII) has long been known to play an important role in learning and memory as well as long term potentiation (LTP). More recently it has been suggested that it might be involved in the time averaging of synaptic signals, which can then lead to the high precision of information stored at a single synapse. However, the role of the scaffolding molecule, neurogranin (Ng), in governing the dynamics of CaMKII is not yet fully understood. In this work, we adopt a rule-based modeling approach through the Monte Carlo method to study the effect of Ca2+ signals on the dynamics of CaMKII phosphorylation in the postsynaptic density (PSD). Calcium surges are observed in synaptic spines during an EPSP and back-propagating action potential due to the opening of NMDA receptors and voltage dependent calcium channels. We study the differences between the dynamics of phosphorylation of CaMKII monomers and dodecameric holoenzymes. The scaffolding molecule Ng, when present in significant concentration, limits the availability of free calmodulin (CaM), the protein which activates CaMKII in the presence of calcium. We show that it plays an important modulatory role in CaMKII phosphorylation following a surge of high calcium concentration. We find a non-intuitive dependence of this effect on CaM concentration that results from the different affinities of CaM for CaMKII depending on the number of calcium ions bound to the former. It has been shown previously that in the absence of phosphatase CaMKII monomers integrate over Ca2+ signals of certain frequencies through autophosphorylation (Pepke et al, Plos Comp. Bio., 2010). We also study the effect of multiple calcium spikes on CaMKII holoenzyme autophosphorylation, and show that in the presence of phosphatase CaMKII behaves as a leaky integrator of calcium signals, a result that has been recently observed in vivo. Our models predict that the parameters of this leaky integrator are finely tuned through the interactions of Ng, CaM, CaMKII, and PP1. This is a possible mechanism to precisely control the sensitivity of synapses to calcium signals.

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.

scholarly journals Cholecystokinin release triggered by NMDA receptors produces LTP and sound–sound associative memory

2019 ◽  
Vol 116 (13) ◽  
pp. 6397-6406 ◽  
Author(s):  
Xi Chen ◽  
Xiao Li ◽  
Yin Ting Wong ◽  
Xuejiao Zheng ◽  
Haitao Wang ◽  
...  
Keyword(s):  
Associative Learning ◽  
Associative Memory ◽  
High Frequency ◽  
Low Frequency ◽  
Long Term Potentiation ◽  
High Frequency Stimulation ◽  
Low Frequency Stimulation ◽  
Term Potentiation ◽  
Frequency Stimulation

Memory is stored in neural networks via changes in synaptic strength mediated in part by NMDA receptor (NMDAR)-dependent long-term potentiation (LTP). Here we show that a cholecystokinin (CCK)-B receptor (CCKBR) antagonist blocks high-frequency stimulation-induced neocortical LTP, whereas local infusion of CCK induces LTP. CCK−/−mice lacked neocortical LTP and showed deficits in a cue–cue associative learning paradigm; and administration of CCK rescued associative learning deficits. High-frequency stimulation-induced neocortical LTP was completely blocked by either the NMDAR antagonist or the CCKBR antagonist, while application of either NMDA or CCK induced LTP after low-frequency stimulation. In the presence of CCK, LTP was still induced even after blockade of NMDARs. Local application of NMDA induced the release of CCK in the neocortex. These findings suggest that NMDARs control the release of CCK, which enables neocortical LTP and the formation of cue–cue associative memory.

Sign in / Sign up

Export Citation Format

Share Document