16 Quantal analysis of excitatory postsynaptic currents at the hippocampal mossy fiber-CA3 pyramidal cell synapse

Author(s):  
Eberhard von Kitzing ◽  
Peter Jonas ◽  
Bert Sakmann
2010 ◽  
Vol 104 (6) ◽  
pp. 3293-3304 ◽  
Author(s):  
Ren-Zhi Zhan ◽  
Olga Timofeeva ◽  
J. Victor Nadler

After experimental status epilepticus, many dentate granule cells born into the postseizure environment migrate aberrantly into the dentate hilus. Hilar ectopic granule cells (HEGCs) have also been found in persons with epilepsy. These cells exhibit a high rate of spontaneous activity, which may enhance seizure propagation. Electron microscopic studies indicated that HEGCs receive more recurrent mossy fiber innervation than normotopic granule cells in the same animals but receive much less inhibitory innervation. This study used hippocampal slices prepared from rats that had experienced pilocarpine-induced status epilepticus to test the hypothesis that an imbalance of synaptic excitation and inhibition contributes to the hyperexcitability of HEGCs. Mossy fiber stimulation evoked a much smaller GABAA receptor–mediated inhibitory postsynaptic currents (IPSC) in HEGCs than in normotopic granule cells from either control rats or rats that had experienced status epilepticus. However, recurrent mossy fiber-evoked excitatory postsynaptic currents (EPSCs) of similar size were recorded from HEGCs and normotopic granule cells in status epilepticus–experienced rats. HEGCs exhibited the highest frequency of miniature excitatory postsynaptic currents (mEPSCs) and the lowest frequency of miniature inhibitory postsynaptic currents (mIPSCs) of any granule cell group. On average, both mEPSCs and mIPSCs were of higher amplitude, transferred more charge per event, and exhibited slower kinetics in HEGCs than in granule cells from control rats. Charge transfer per unit time in HEGCs was greater for mEPSCs and much less for mIPSCs than in the normotopic granule cell groups. A high ratio of excitatory to inhibitory synaptic function probably accounts, in part, for the hyperexcitability of HEGCs.


1997 ◽  
Vol 77 (3) ◽  
pp. 1075-1086 ◽  
Author(s):  
Darrell A. Henze ◽  
J. Patrick Card ◽  
German Barrionuevo ◽  
Yezekiel Ben-Ari

Henze, Darrell A., J. Patrick Card, German Barrionuevo, and Yezekiel Ben-Ari. Large amplitude miniature excitatory postsynaptic currents in hippocampal CA3 pyramidal neurons are of mossy fiber origin. J. Neurophysiol. 77: 1075–1086, 1997. Neonatal (P0) γ-irradiation was used to lesion selectively the mossy fiber (MF) synaptic input to CA3 pyramidal cells. This lesion caused a >85% reduction in the MF input as determined by quantitative assessment of the number of dynorphin immunoreactive MF boutons. Theγ-irradiation lesion caused a reduction in the mean number of miniature excitatory postsynaptic currents (mEPSCs) recorded from CA3 pyramidal cells (2,292 vs. 1,429/3-min period; n = 10). The lesion also caused a reduction in the mean mEPSC peak amplitude from 19.1 ± 0.45 to 14.6 ± 0.49 pA (mean ± SE; peak conductance 238.8 ± 5.6 to 182.0 ± 6.1 pS). Similarly, there was a reduction in the mean 10–85% rise time from 1.72 ± 0.02 ms to 1.42 ± 0.04 ms. The effects of the γ-irradiation on both mEPSC amplitude and 10–85% rise time were significant at P < 0.002 and P < 0.005 (2-tailed Kolmogorov-Smirnov test). Based on the selectivity of the γ-irradiation, MF and non-MF mEPSC amplitude and 10–85% rise-time distributions were calculated. Both the amplitude and 10–85% rise-time distributions showed extensive overlap between the MF and non-MF mediated mEPSCs. The MF mEPSC distributions had a mean peak amplitude of 24.6 pA (307.5 pS) and a mean 10–85% rise time of 2.16 ms. The non-MF mEPSC distributions had a mean peak amplitude of 12.2 pA (152.5 pS) and 10–85% rise time of 1.26 ms. The modes of the amplitude distributions were the same at 5 pA (62 pS). The MF and non-MF mEPSC amplitude and 10–85% rise-time distributions were significantly different at P ≪ 0.001 (1-tailed, large sample Kolmogorov-Smirnov test). The data demonstrate that the removal of the MF synaptic input to CA3 pyramidal cells leads to the absence of the large amplitude mEPSCs that are present in control recordings.


eNeuro ◽  
2021 ◽  
pp. ENEURO.0450-20.2021
Author(s):  
Sachin Makani ◽  
Stefano Lutzu ◽  
Pablo J. Lituma ◽  
David L. Hunt ◽  
Pablo E. Castillo

Synapse ◽  
2020 ◽  
Vol 74 (12) ◽  
Author(s):  
Simon Chamberland ◽  
Yulia Timofeeva ◽  
Alesya Evstratova ◽  
Christopher A. Norman ◽  
Kirill Volynski ◽  
...  

2002 ◽  
Vol 87 (1) ◽  
pp. 15-29 ◽  
Author(s):  
Darrell A. Henze ◽  
David B. T. McMahon ◽  
Kristen M. Harris ◽  
German Barrionuevo

The mechanisms generating giant miniature excitatory postsynaptic currents (mEPSCs) were investigated at the hippocampal mossy fiber (MF) to CA3 pyramidal cell synapse in vitro. These giant mEPSCs have peak amplitudes as large as 1,700 pA (13.6 nS) with a mean maximal mEPSC amplitude of 366 ± 20 pA (mean ± SD; 5 nS; n = 25 cells). This is compared with maximal mEPSC amplitudes of <100 pA typically observed at other cortical synapses. We tested the hypothesis that giant mEPSCs are due to synchronized release of multiple vesicles across the release sites of single MF boutons by directly inducing vesicular release using secretagogues. If giant mEPSCs result from simultaneous multivesicular release, then secretagogues should increase the frequency of small mEPSCs selectively. We found that hypertonic sucrose and spermine increased the frequency of both small and giant mEPSCs. The peptide toxin secretagogues alpha-latrotoxin and pardaxin failed to increase the frequency of giant mEPSCs, but the possible lack of tissue penetration of the toxins make these results equivocal. Because a multiquantal release mechanism is likely to be mediated by a spontaneous increase in presynaptic calcium concentration, a monoquantal mechanism is further supported by results that giant mEPSCs were not affected by manipulations of extracellular or intracellular calcium concentrations. In addition, reducing the temperature of the bath to 15°C failed to desynchronize the rising phases of giant mEPSCs. Together these data suggest that the giant mEPSCs are generated via a monovesicular mechanism. Three-dimensional analysis through serial electron microscopy of the MF boutons revealed large clear vesicles (50 to 160 nm diam) docked presynaptically at the MF synapse in sufficient numbers to account for the amplitude and frequency of giant mEPSCs recorded electrophysiologically. It is concluded that release of the contents of a single large clear vesicle generates giant mEPSCs at the MF to CA3 pyramidal cell synapse.


1998 ◽  
Vol 79 (4) ◽  
pp. 2013-2024 ◽  
Author(s):  
Albert Y. Hsia ◽  
Robert C. Malenka ◽  
Roger A. Nicoll

Hsia, Albert Y., Robert C. Malenka, and Roger A. Nicoll. Development of excitatory circuitry in the hippocampus. J. Neurophysiol. 79: 2013–2024, 1998. Assessing the development of local circuitry in the hippocampus has relied primarily on anatomic studies. Here we take a physiological approach, to directly evaluate the means by which the mature state of connectivity between CA3 and CA1 hippocampal pyramidal cells is established. Using a technique of comparing miniature excitatory postsynaptic currents (mEPSCs) to EPSCs in response to spontaneously occurring action potentials in CA3 cells, we found that from neonatal to adult ages, functional synapses are created and serve to increase the degree of connectivity between CA3-CA1 cell pairs. Neither the probability of release nor mean quantal size was found to change significantly with age. However, the variability of quantal events decreases substantially as synapses mature. Thus in the hippocampus the developmental strategy for enhancing excitatory synaptic transmission does not appear to involve an increase in the efficacy at individual synapses, but rather an increase in the connectivity between cell pairs.


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