PMID-26516682 Retroactive modulation of spike timing-dependent plasticity by dopamine.
- Here we show that dopamine, a positive reinforcement signal, can retroactively convert hippocampal timing-dependent synaptic depression into potentiation.
- This effect requires functional NMDA receptors and is mediated in part through the activation of the cAMP/PKA cascade.
- Mouse horizontal slices.
- Plasticity induced by 100 pairings of a single EPSP followed by a postsynaptic spike (heavy-handed?)
- Pre-before-post @ 10ms -> LTP
- Post-before-pre @ -20ms -> LTD
- Post-before-pre @ -10ms -> LTP (?!)
- Addition of Dopamine antagonist (D2: sulpiride, D1/D5: SCH23390) prevented LTP and resulted in LTD.
- Post-before-pre @ -20ms -> LTP in the presence of 20 uM DA.
- The presence of DA during coordinated spiking activity widense the timing interval for induction of LTP.
- What about if it's applied afterward?
- 20 uM DA applied 1 minute (for 10-12 minutes) after LTD induction @ -20 mS converted LTD into LTP.
- This was corrected by addition of the DA agonists.
- Did not work if DA was applied 10 or 30 minutes after the LTD induction.
- Others have shown that this requires functional NMDA receptors.
- Application of NMDA agonist D-AP5 after post-before-pre -20ms did not affect LTD.
- Application of D-AP5 before DA partially blocked conversion of LTD to LTP.
- Application of D-AP5 alone before induction did not affect LTD.
- This is dependent on the cAMP/PKA signaling cascade:
- Application of forskolin (andenylyl cyclase AC activator) converts LTD -> LTP.
- Dependent on NMDA.
- PKA inhibitor H-89 alsoblocked LTD -> P.
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