Lysophosphatidic acid selectively modulates excitatory transmission in hippocampal neurons.

BACKGROUND

Lysophosphatidic acid (LPA) is a bioactive phospholipid that affects hippocampal excitatory synaptic transmission.

RESULTS

Here we provide in vitro evidence that LPA elicits intracellular calcium concentration ([Ca]) transients by LPA receptor activation in primary cultured hippocampal mouse neurons. Downstream and via G-coupling, this led to phospholipase C (PLC) activation, inositol (1,4,5) trisphosphate (IP)-induced Ca release (IICR) and voltage gated Ca channel activation. In addition, we found that LPA elevated [Ca], not only in the soma but also in presynaptic terminals. This altered the frequency of spontaneous vesicle release specifically in excitatory synapses. However, against our expectations, LPA reduced the frequency of miniature excitatory postsynaptic currents. This was due to a depletion of releasable vesicles resulting from a slowed recycling. SynaptopHluorin based measurements indicated a transient augmentation of release followed by prolonged persistence of vesicles at the membrane. Concordant to our previous findings on ex vivo brain slices, LPA increased spontaneous glutamatergic vesicle release in Banker style astrocytic co-cultures. Our results indicate that pro-excitatory LPA effects critically depend on stable vesicle pools.

CONCLUSIONS

Taken together, our data further support membrane derived phospholipids as active modulators of excitatory synaptic transmission.