Abstract
The firing of striatal projection neurons (SPNs) exhibits afterhyperpolarizing potentials (AHPs) that determine discharge frequency. They are in part generated by Ca2+-activated K+-currents involving BK and SK components. It has previously been shown that suprathreshold corticostriatal responses are more prolonged and evoke more action potentials in direct pathway SPNs (dSPNs) than in indirect pathway SPNs (iSPNs). In contrast, iSPNs generate dendritic autoregenerative responses. Using whole cell recordings in brain slices, we asked whether the participation of Ca2+-activated K+-currents plays a role in these responses. Secondly, we asked if these currents may explain some differences in synaptic integration between dSPNs and iSPNs. Neurons obtained from BAC D1 and D2 GFP mice were recorded. We used charybdotoxin and apamin to block BK and SK channels, respectively. Both antagonists increased the depolarization and delayed the repolarization of suprathreshold corticostriatal responses in both neuron classes. We also used NS 1619 and NS 309 (CyPPA), to enhance BK and SK channels, respectively. Current enhancers hyperpolarized and accelerated the repolarization of corticostriatal responses in both neuron classes. Nevertheless, these drugs made evident that the contribution of Ca2+-activated K+-currents was different in dSPNs as compared to iSPNs: in dSPNs their activation was slower as though calcium took a diffusion delay to activate them. In contrast, their activation was fast and then sustained in iSPNs as though calcium flux activates them at the moment of entry. The blockade of Ca2+-activated K+-currents made iSPNs to look as dSPNs. Conversely, their enhancement made dSPNs to look as iSPNs. It is concluded that Ca2+-activated K+-currents are a main intrinsic determinant causing the differences in synaptic integration between corticostriatal polysynaptic responses between dSPNs and iSPNs.
Highlights
Ca2+-activated K+-currents are important regulators of excitability: they control firing frequency and synaptic integration (Bond et al, 2005; Salkoff et al, 2006; Faber, 2009)
We previously reported that suprathreshold corticostriatal responses are more prolonged and evoke more action potentials in direct pathway striatal projection neurons (SPNs) (dSPNs) than in indirect pathway SPNs (iSPNs) (FloresBarrera et al, 2010) and that their duration depends on polysynaptic activity (Vizcarra-Chacon et al, 2013) involving both cortical and striatal neurons as well as intrinsic currents (Vergara et al, 2003; Flores-Barrera et al, 2009, 2011)
Note that hyperpolarizations induced by Ca2+-activated K+-currents rise slowly and lasts hundreds of milliseconds, suggesting that, after synaptic activation, Ca-entry takes some time to activate BK- and SK-channels in dSPNs
Summary
Ca2+-activated K+-currents are important regulators of excitability: they control firing frequency and synaptic integration (Bond et al, 2005; Salkoff et al, 2006; Faber, 2009). In striatal projection neurons (SPNs), Ca2+-activated K+-currents contribute to action potential repolarization and the afterhyperpolarization that makes up a great part of the interspike interval during repetitive firing (Pineda et al, 1992; Vilchis et al, 2000; Pérez-Garci et al, 2003; Pérez-Rosello et al, 2005; Wolf et al, 2005; Galarraga et al, 2007; Flores-Barrera et al, 2009). Selective peptidic toxins made clear that Ca2+-activated K+ currents in SPNs comprise “small” SK and “large” BK conductance channels (Pineda et al., 1992; Bargas et al, 1999). These channels are important targets for the actions of neurotransmitters, e.g.: dopamine, acetylcholine and somatostatin, among others CaV1 and CaV2.3 calcium channel represent a much smaller Ca2+ source (Vilchis et al, 2000)
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