Neuroscience 2002 Abstract
| Presentation Number: | 149.8 |
|---|---|
| Abstract Title: | PROTEIN KINASE A MODULATES LTP INDUCTION BY INCREASING CALCIUM PERMEABILITY OF NMDA RECEPTORS. |
| Authors: |
Castillo, P. E.*1
; Chevaleyre, V.1
; Goldberg, J. H.2
; Yuste, R.2
; Zukin, R. S.1
; Bennett, M. V. L.1
1Dept Neurosci, Albert Einstein Col Med, Bronx, NY 2Dept Biological Sci, Columbia Univ, New York, NY |
| Primary Theme and Topics |
Synaptic Transmission and Excitability - Synaptic Plasticity -- Long-term potentiation (LTP) |
| Secondary Theme and Topics | Synaptic Transmission and Excitability<br />- Synaptic Transmission<br />-- Postsynaptic mechanisms: Excitatory |
| Session: |
149. Synaptic plasticity: long-term potentiation I Poster |
| Presentation Time: | Sunday, November 3, 2002 4:00 PM-5:00 PM |
| Location: | Hall A2-B3 E-21 |
| Keywords: | CA1, synaptic plasticity, kinase, hippocampus |
Calcium influx through NMDA receptors (NMDARs) is critical to some forms of synaptic plasticity. By modulating NMDAR function, different kinases can regulate induction of long-term potentiation (LTP). Although cAMP-dependent signaling has been implicated in the early phase of NMDAR-dependent LTP, the precise molecular mechanism is unknown. It has recently been suggested that phosphorylation by PKA selectively enhances NMDARs Ca2+ permeability (V.A. Skeberdis et al; SFN. Abstract 261.3, 2001), a mechanism that may be relevant to LTP induction.
Here, we examined the effect of PKA inhibition on the early phase of NMDAR-dependent LTP at Schaffer collateral-CA1 synapses in acute mouse hippocampal slices and directly monitored calcium influx into CA1 pyramidal cell spines by two-photon imaging. Bath application of the PKA inhibitors H-89 or PKI 30 min before tetanic stimulation markedly reduced the magnitude of early LTP, with no effect on previously established LTP or basal synaptic transmission. As expected if this effect were due to a reduction in Ca2+ permeability through NMDA channels, increase in extracellular Ca2+ to 5 mM after PKA blockade and just prior to the tetanus rescued LTP to the control level. Furthermore, NMDAR-dependent Ca2+ influx at spines, induced by local synaptic activation, was reduced by ~60% after PKA blockade whereas action potential-dependent Ca2+ signals were unchanged. These findings indicate the importance of cAMP signaling to early LTP at CA1 synapses and suggest that a key function of PKA in LTP induction is increasing Ca2+ permeability of NMDARs.
Here, we examined the effect of PKA inhibition on the early phase of NMDAR-dependent LTP at Schaffer collateral-CA1 synapses in acute mouse hippocampal slices and directly monitored calcium influx into CA1 pyramidal cell spines by two-photon imaging. Bath application of the PKA inhibitors H-89 or PKI 30 min before tetanic stimulation markedly reduced the magnitude of early LTP, with no effect on previously established LTP or basal synaptic transmission. As expected if this effect were due to a reduction in Ca2+ permeability through NMDA channels, increase in extracellular Ca2+ to 5 mM after PKA blockade and just prior to the tetanus rescued LTP to the control level. Furthermore, NMDAR-dependent Ca2+ influx at spines, induced by local synaptic activation, was reduced by ~60% after PKA blockade whereas action potential-dependent Ca2+ signals were unchanged. These findings indicate the importance of cAMP signaling to early LTP at CA1 synapses and suggest that a key function of PKA in LTP induction is increasing Ca2+ permeability of NMDARs.
Supported by NIH grants NS 20752
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2002 Neuroscience Meeting Planner. Orlando, FL: Society for Neuroscience, 2002. Online.
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