Differences in synaptic integration between direct and indirect striatal projection neurons: Role of Ca_V 3 channels

Different corticostriatal suprathreshold responses in direct and indirect striatal projection neurons (SPNs) of rodents have been reported. Responses consist in prolonged synaptic potentials of polysynaptic and intrinsic origin, in which voltage-gated Ca² ⁺ currents play a role. Recording simultaneous Ca² ⁺ imaging and voltage responses at the soma, while activating the corticostriatal pathway, we show that encoding of synaptic responses into trains of action potentials (APs) is different in SPNs: firing of APs in D1-SPNs increase gradually, in parallel with Ca² ⁺ entry, as a function of stimulus intensity. In contrast, D2-SPNs attain a maximum number of evoked spikes at low stimulus intensities, Ca² ⁺ entry is limited, and both remain the same in spite of increasing stimulus strength. Stimulus needs to reach certain intensity, to have propagated Ca² ⁺ potentials to the soma plus a sudden step in Ca² ⁺ entry, without changing the number of fired APs, phenomena never seen in D1-SPNs. Constant firing in spite of changing stimulus, suggested the involvement of underlying inactivating potentials. We found that Caᵥ3 currents contribute to Ca²⁺ entry in both classes of SPNs, but have a more notable effect in D2-SPNs, where a low-threshold spike was disclosed. Blockade of Ca_V 3 channels retarded the steep rise in firing in D2-SPNs. Inhibition block increased the number of spikes fired by D2-SPNs, without changing firing in D1-SPNs. These differences in synaptic integration enable a biophysical dissimilarity: dendritic inhibition appears to be more relevant for D2-SPNs. This may imply distinctions in the set of interneurons affecting each SPN class.