Dopamine induces release of calcium from internal stores in layer II lateral entorhinal cortex fan cells

The entorhinal cortex plays an important role in temporal lobe processes including learning and memory, object recognition, and contextual information processing. The alteration of the strength of synaptic inputs to the lateral entorhinal cortex may therefore contribute substantially to sensory and mnemonic functions. The neuromodulatory transmitter dopamine exerts powerful effects on excitatory glutamatergic synaptic transmission in the entorhinal cortex. Interestingly, inputs from midbrain dopamine neurons appear to specifically target clusters of excitatory cells located in the superficial layers of the entorhinal cortex. We have previously demonstrated that dopamine facilitates synaptic transmission through the activation of D₁-like receptors. This facilitation of synaptic transmission is dependent on both activation of classical D₁-like-receptors, and upon activation of dopamine receptors linked to increases in phospholipase C, inositol triphosphate (IP₃), and intracellular calcium. In the present study we combined electrophysiological recordings of evoked excitatory postsynaptic currents with imaging of intracellular calcium using the fluorescent indicator fluo-4 to monitor calcium transients evoked by dopamine in electrophysiologically identified putative fan and pyramidal cells of the lateral entorhinal cortex. Bath application of dopamine (1 μM), or the phosphatidylinositol (PI)-linked D₁-like-receptor agonist SKF83959 (5 μM), induced reliable and reversible increases in fluo-4 fluorescence and excitatory postsynaptic currents in fan cells, but not in pyramidal cells. In contrast, application of the classical D₁-like-receptor agonist SKF38393 (10 μM) did not result in significant increases in fluorescence. Blocking release of calcium from internal stores by loading cells with the IP₃ receptor blocker heparin (1 mM) or the ryanodine receptor blocker dantrolene (20 μM) abolished both the calcium transients and the facilitation of evoked synaptic currents induced by dopamine. Dopamine also induced calcium transients in fan cells when calcium was excluded from the extracellular medium, further indicating that the calcium transients are linked to release from internal stores. These results indicate that following D₁-like-receptor binding, dopamine selectively induces transient elevations in intracellular calcium via activation of IP₃ and ryanodine receptors, and that these elevations are linked to the facilitation of synaptic responses in putative layer II entorhinal cortex fan cells.