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Large amplitude miniature excitatory postsynaptic currents in hippocampal CA3 pyramidal neurons are of mossy fiber
D A Henze1, J P Card, G Barrionuevo
1Department of Neuroscience, University of Pittsburgh, Pennsylvania 15260, USA.
Abstract:
Neonatal (P0) gamma-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. The gamma-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 gamma-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 selectively of the gamma-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.
Insights
Neonatal gamma-irradiation selectively lesioned mossy fiber (MF) input to CA3 cells, significantly reducing miniature excitatory postsynaptic currents (mEPSCs). This study quantifies the impact of MF input loss on CA3 pyramidal cell synaptic function.
Area of Science:
- Neuroscience
- Cellular and Molecular Neuroscience
- Synaptic Plasticity
Background:
- Mossy fiber (MF) pathways are crucial for hippocampal information processing.
- Understanding MF synaptic input is vital for deciphering CA3 pyramidal cell function.
- Selective lesioning techniques are essential for dissecting neural circuit contributions.
Purpose of the Study:
- To investigate the specific contribution of MF synaptic input to CA3 pyramidal cell activity.
- To quantify the changes in miniature excitatory postsynaptic currents (mEPSCs) following MF pathway disruption.
- To differentiate between MF-mediated and non-MF-mediated synaptic events in CA3 cells.
Main Methods:
- Neonatal (P0) gamma-irradiation was employed to selectively lesion MF synaptic input to CA3 pyramidal cells.
- Quantitative assessment of dynorphin immunoreactive MF boutons determined lesion efficacy (>85% reduction).
- Electrophysiological recordings of mEPSCs in CA3 pyramidal cells were analyzed for amplitude, rise time, and frequency.
Main Results:
- Gamma-irradiation significantly reduced mEPSC frequency, peak amplitude, and 10-85% rise time in CA3 pyramidal cells.
- Calculated MF mEPSC distributions showed a mean peak amplitude of 24.6 pA and a 10-85% rise time of 2.16 ms.
- Non-MF mEPSC distributions exhibited a lower mean peak amplitude of 12.2 pA and a 1.26 ms rise time, with significant differences between MF and non-MF events.
Conclusions:
- Selective removal of MF synaptic input to CA3 pyramidal cells leads to a significant reduction in mEPSC amplitude and alterations in kinetics.
- The study successfully differentiated MF and non-MF mediated synaptic currents based on electrophysiological properties.
- These findings highlight the critical role of MF input in shaping the synaptic currents of CA3 pyramidal cells.