Dopamine induced switch in the subthreshold dynamics of the striatal cholinergic interneurons: A numerical study

The striatum is a part of the basal ganglia, which are a group of nuclei in the brain associated with motor control, cognition and learning. Striatal cholinergic interneurons (AchNs) play a crucial role in these functions. AchNs are tonically active in vivo and in vitro  , and are able to fire in the absence of synaptic inputs. AchNs respond to sensory stimuli and sensorimotor learning by transiently suppressing their firing activity. This pause is dopamine signal sensitive, but the neurophysiological mechanism of the dopaminergic influence is under debate. Both the regular spiking response as well as the pause response are influenced by the inwardly rectifying outward GkirGkir, a slow hyperpolarization activated noninactivating GhGh, and calcium and calcium-dependent potassium conductances [Wilson, C., Goldberg, J., 2006. Origin of the slow afterhyperpolarization and slow rhythmic bursting in striatal cholinergic interneurons. J. Neurophysiol. 95(1), 196–204; Wilson, C., 2005. The mechanism of intrinsic amplification of hyperpolarizations and spontaneous bursting in striatal cholinergic interneurons. Neuron 45(4), 575–585]. Recent experimental evidence has shown that dopaminergic modulations on GhGh, GkirGkir and calcium conductances influence the AchN's excitability [Deng, P., Zhang, Y., Xu, Z., 2007. Involvement of I(h  ) in dopamine modulation of tonic firing in striatal cholinergic interneurons. J. Neurosci. 27(12), 3148–3156; Aosaki, T., Kiuchi, K., Kawaguchi, Y., 1998. Dopamine D1D1-like receptor activation excites rat striatal large aspiny neurons in vitro. J. Neurosci. 18(14), 5180–5190]. We employed computational models of the AchN to analyze the conductance based dopaminergic changes. We analyzed the robustness of these subthreshold oscillations and how they are affected by dopaminergic modulation. Our results predict that these conductances allow the dopamine to switch the AchN between stable oscillatory and fixed-point behaviors. The present approach and results show that dopamine receptors (D1D1 and D2D2) mediate opposing effects on this switch and therefore on the suprathreshold excitability as well. The switching effect of the dopaminergic signal is the major qualitative feature that can serve as a building block for higher network-level descriptions. To our knowledge this is the first paper that synthesizes the growing body of experimental literature about the dopaminergic modulation of the AchNs into a modelling framework.