Pertussis toxin prevents induction of hippocampal long-term potentiation in the stratum radiatum and stratum oriens inputs to CA1 neurons

In hippocampal slices, temporary (10–20 min) replacement of glucose with 10 mM 2-deoxyglucose is followed by marked and very sustained potentiation of EPSPs (2-DG LTP). To investigate its mechanism, we examined 2-DG's effect in CA1 neurons recorded with sharp 3 M KCl electrodes containing a strong chelator, 50 or 100 mM ethylene glycol-bis(β-aminoethyl ether)- N, N, N′, N′-tetraacetic acid (EGTA). In most cases, field EPSPs were simultaneously recorded and conventional LTP was also elicited in some cells by tetanic stimulation of stratum radiatum. 2-DG potentiated intracellular EPSP slopes by 48 ± 5.1% (SE) in nine cells recorded with plain KCl electrodes and by 52 ± 6.2% in seven cells recorded with EGTA-containing electrodes. In four of the latter cells, tetanic stimulation (twice 100 Hz for 1 s) failed to evoke LTP (2 ± 1.1%), although field EPSPs were clearly potentiated (by 28 ± 6.9%). Thus unlike tetanic LTP, 2-DG LTP is not readily prevented by postsynaptic intraneuronal injection of EGTA. These findings agree with other evidence that the rise in postsynaptic (somatic) [Ca2+]i caused by 2-DG is not the principal trigger for the subsequent 2-DG LTP and that it may be a purely presynaptic phenomenon.

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Mechanisms of heterosynaptic metaplasticity

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2013.0148 ◽

2014 ◽

Vol 369 (1633) ◽

pp. 20130148 ◽

Cited By ~ 44

Author(s):

Sarah R. Hulme ◽

Owen D. Jones ◽

Clarke R. Raymond ◽

Pankaj Sah ◽

Wickliffe C. Abraham

Keyword(s):

Synaptic Plasticity ◽

Long Range ◽

Intercellular Communication ◽

Atp Hydrolysis ◽

Long Term Potentiation ◽

Stratum Radiatum ◽

Signalling Pathways ◽

Stratum Oriens ◽

Term Potentiation

Synaptic plasticity is fundamental to the neural processes underlying learning and memory. Interestingly, synaptic plasticity itself can be dynamically regulated by prior activity, in a process termed ‘metaplasticity’, which can be expressed both homosynaptically and heterosynaptically. Here, we focus on heterosynaptic metaplasticity, particularly long-range interactions between synapses spread across dendritic compartments, and review evidence for intra cellular versus inter cellular signalling pathways leading to this effect. Of particular interest is our previously reported finding that priming stimulation in stratum oriens of area CA1 in the hippocampal slice heterosynaptically inhibits subsequent long-term potentiation and facilitates long-term depression in stratum radiatum. As we have excluded the most likely intracellular signalling pathways that might mediate this long-range heterosynaptic effect, we consider the hypothesis that intercellular communication may be critically involved. This hypothesis is supported by the finding that extracellular ATP hydrolysis, and activation of adenosine A2 receptors are required to induce the metaplastic state. Moreover, delivery of the priming stimulation in stratum oriens elicited astrocytic calcium responses in stratum radiatum. Both the astrocytic responses and the metaplasticity were blocked by gap junction inhibitors. Taken together, these findings support a novel intercellular communication system, possibly involving astrocytes, being required for this type of heterosynaptic metaplasticity.

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Associative spike timing-dependent potentiation of the basal dendritic excitatory synapses in the hippocampus in vivo

Journal of Neurophysiology ◽

10.1152/jn.00188.2016 ◽

2016 ◽

Vol 115 (6) ◽

pp. 3264-3274 ◽

Cited By ~ 6

Author(s):

Thomas K. Fung ◽

Clayton S. Law ◽

L. Stan Leung

Keyword(s):

Current Source ◽

Long Term Potentiation ◽

Spike Timing ◽

Stratum Radiatum ◽

Adult Rats ◽

Synaptic Excitation ◽

Stratum Oriens ◽

Term Potentiation

Spike timing-dependent plasticity in the hippocampus has rarely been studied in vivo. Using extracellular potential and current source density analysis in urethane-anesthetized adult rats, we studied synaptic plasticity at the basal dendritic excitatory synapse in CA1 after excitation-spike (ES) pairing; E was a weak basal dendritic excitation evoked by stratum oriens stimulation, and S was a population spike evoked by stratum radiatum apical dendritic excitation. We hypothesize that positive ES pairing—generating synaptic excitation before a spike—results in long-term potentiation (LTP) while negative ES pairing results in long-term depression (LTD). Pairing (50 pairs at 5 Hz) at ES intervals of −10 to 0 ms resulted in significant input-specific LTP of the basal dendritic excitatory sink, lasting 60–120 min. Pairing at +10- to +20-ms ES intervals, or unpaired 5-Hz stimulation, did not induce significant basal dendritic or apical dendritic LTP or LTD. No basal dendritic LTD was found after stimulation of stratum oriens with 200 pairs of high-intensity pulses at 25-ms interval. Pairing-induced LTP was abolished by pretreatment with an N-methyl-d-aspartate receptor antagonist, 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), which also reduced spike bursting during 5-Hz pairing. Pairing at 0.5 Hz did not induce spike bursts or basal dendritic LTP. In conclusion, ES pairing at 5 Hz resulted in input-specific basal dendritic LTP at ES intervals of −10 ms to 0 ms but no LTD at ES intervals of −20 to +20 ms. Associative LTP likely occurred because of theta-rhythmic coincidence of subthreshold excitation with a backpropagated spike burst, which are conditions that can occur naturally in the hippocampus.

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

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2002.1217 ◽

2003 ◽

Vol 358 (1432) ◽

pp. 689-693 ◽

Cited By ~ 9

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.

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