Neuroscience 2005 Abstract
| Presentation Number: | 496.3 |
|---|---|
| Abstract Title: | Constitutive Src-family kinase activity is required for NMDA receptor-dependent Hebbian LTP in inhibitory interneurons. |
| Authors: |
Lamsa, K.*1
; Heeroma, J.1
; Rusakov, D. A.1
; Kullmann, D. M.1
1Inst. Neurol., UCL, London, United Kingdom |
| Primary Theme and Topics |
Neural Excitability, Synapses, and Glia: Cellular Mechanisms - Synaptic Plasticity -- LTP: Kinases and intracellular signaling |
| Secondary Theme and Topics | Neural Excitability, Synapses, and Glia: Cellular Mechanisms<br />- Synaptic Plasticity<br />-- LTP: Postsynaptic mechanisms |
| Session: |
496. LTP Signaling: Other Kinases Poster |
| Presentation Time: | Monday, November 14, 2005 3:00 PM-4:00 PM |
| Location: | Washington Convention Center - Hall A-C, Board # H4 |
| Keywords: | TYROSINE KINASE, ACTIVITY-DEPENDENT, GABAERGIC, IPSP |
We recently showed that pairing low-frequency presynaptic activity with postsynaptic depolarization evokes NMDAR-mediated Hebbian LTP in hippocampal CA1 feed-forward inhibitory interneurons (Lamsa et al, SFN 2004). Here we report that NMDARs in interneurons require constitutive activation by Src-family kinases (SFKs).
We isolated NMDAR-mediated EPSPs in stratum radiatum interneurons of rat slices by recording in picrotoxin (100 µM), NBQX (10 µM) and 0 [Mg2+]. NMDAR-mediated EPSPs were detected in every one of 54 cells recorded via a gramicidin perforated patch. SFK inhibitors (10 µM lavendustin A or 50 µM genistein) reversibly attenuated NMDAR-mediated EPSPs. When recorded in whole-cell mode, NMDAR-mediated EPSP/Cs attenuated rapidly or disappeared altogether, in contrast to AMPA/kainateR-mediated responses which remained stable. Run-down was prevented when the Src-activating peptide [H]EPQ[pTyr]EEPIA[OH] (10 µM) was included in the pipette. Run-down could also be reversed by withdrawing the whole-cell pipette while continuing to record from the same cell via a perforated patch.
NMDAR-mediated EPSPs recorded in perforated patch mode were substantially although transiently enhanced by postsynaptic spike trains. This enhancement was blocked by SFK inhibitors. Pairing-evoked Hebbian LTP in interneurons was also blocked by the inhibitors.
We also showed that pairing pre- and postsynaptic activity failed to evoke LTP in whole-cell mode. However, after the whole cell pipette was withdrawn and recording continued via a perforated patch, a second pairing led to LTP in 5/8 cells, similar to the fraction of interneurons that exhibit LTP without prior whole-cell dialysis.
We conclude that NMDARs in inteneurons are unusually labile, although they can recover from a period of whole cell recording, and that they require constitutive activation by SFKs. Because SFK activation by spike trains can further enhance NMDAR-mediated signaling, we speculate that the ability of interneurons to exhibit LTP can be modulated.
We isolated NMDAR-mediated EPSPs in stratum radiatum interneurons of rat slices by recording in picrotoxin (100 µM), NBQX (10 µM) and 0 [Mg2+]. NMDAR-mediated EPSPs were detected in every one of 54 cells recorded via a gramicidin perforated patch. SFK inhibitors (10 µM lavendustin A or 50 µM genistein) reversibly attenuated NMDAR-mediated EPSPs. When recorded in whole-cell mode, NMDAR-mediated EPSP/Cs attenuated rapidly or disappeared altogether, in contrast to AMPA/kainateR-mediated responses which remained stable. Run-down was prevented when the Src-activating peptide [H]EPQ[pTyr]EEPIA[OH] (10 µM) was included in the pipette. Run-down could also be reversed by withdrawing the whole-cell pipette while continuing to record from the same cell via a perforated patch.
NMDAR-mediated EPSPs recorded in perforated patch mode were substantially although transiently enhanced by postsynaptic spike trains. This enhancement was blocked by SFK inhibitors. Pairing-evoked Hebbian LTP in interneurons was also blocked by the inhibitors.
We also showed that pairing pre- and postsynaptic activity failed to evoke LTP in whole-cell mode. However, after the whole cell pipette was withdrawn and recording continued via a perforated patch, a second pairing led to LTP in 5/8 cells, similar to the fraction of interneurons that exhibit LTP without prior whole-cell dialysis.
We conclude that NMDARs in inteneurons are unusually labile, although they can recover from a period of whole cell recording, and that they require constitutive activation by SFKs. Because SFK activation by spike trains can further enhance NMDAR-mediated signaling, we speculate that the ability of interneurons to exhibit LTP can be modulated.
Supported by the MRC and Wellcome Trust
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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