Neuromodulator-evoked synaptic metaplasticity in a CPG

Mark D. Kvarta, Ronald M. Harris-Warrick and Bruce R. Johnson

Metaplasticity (Philpot et al. 1999): Characteristics of activity-dependent changes in synaptic strength altered by neuromodulation (Fischer et al. 1997; Kreitzer and Regehr 2000; Parker 2001; Parker and Grillner 1999; Qian and Delaney 1997).

In this study, the authors showed amines (5-HT, DA, and OA) change the properties of homosynaptic plasticity of a specific graded synapse in STG. The synapse used in this study was PD-to-LP synapse. This is apparently due to modification of vesicle traffic dynamics but the authors did not further dig experimentally into the vesicle release dynamics referring to the readily releasable pool sizes and replenishment rates. Recovery rate of homosynaptic depression was also dependent on the presynaptic activity. The authors discussed that maintained presynaptic depolarization would cause more calcium influx, which consequently increases mobilization of the recovery process.

Dopamine had reliable, significant and independent effects to accelerate the time course of synaptic depression onset and recovery from synaptic depression. It consistently accelerated both the onset of, and the recovery from, synaptic depression. This acceleration of onset and recovery from depression did not depend on the sign of the rather variable DA effect on gIPSP amplitudes described above.

DA had weak and highly variable effects on the LP gIPSPs in different preparations. It increased the rate of synaptic depression and of recovery from it. The variability to DA responses cane be caused by the known opposing effects of DA to decrease pre-synaptic PD transmitter release and increase post-synaptic LP input resistance (Harris-Warrick and Johnson 2010), but to differing amounts in different preparations.

DA may be acting postsynaptically to accelerate the kinetics of transmitter receptor desensitization and recovery from desensitization (Papke et al. 2011).

Octopamine - Increased both initial and steady amplitude, slowed the onset of synaptic depression, while speeding up the recovery rate from depression.

- What about contribution of post-synaptic receptors?

Serotonin - Serotonin depresses the synapse and accelerated the time course of synaptic depression measured with square pulse PD stimulation, but not reach statistical significance for oscillation.

The authors stated in the discussion that individual parameters of synaptic strength can be independently modulated by each amine. I disagree. The synaptic strengh should be determined by the fraction of readily releasable pool activated by depolarization, which must be under a strong influence of the vesicle replenishment rates. I don't think they are independent.