Role of a Striatal Slowly Inactivating Potassium Current in Short-Term Facilitation of Corticostriatal Inputs: A Computer Simulation Study

Abstract

Striatal output neurons (SONs) integrate glutamatergic synaptic inputs originating from the cerebral cortex. In vivo electrophysiological data have shown that a prior depolarization of SONs induced a short-term (Յ1 sec) increase in their membrane excitability, which facilitated the ability of corticostriatal synaptic potentials to induce firing. Here we propose, using a computational model of SONs, that the use-dependent, short-term increase in the responsiveness of SONs mainly results from the slow kinetics of a voltage-dependent, slowly inactivating potassium A-current. This mechanism confers on SONs a form of intrinsic short-term memory that optimizes the synaptic input-output relationship as a function of their past activation.The striatum, the main input stage of the basal ganglia, provides a dynamic neural network that is involved in adaptive control of behavior (for review, see Graybiel 1995). To achieve this function, GABAergic striatal output neurons (SONs) integrate glutamatergic synaptic inputs from many converging cortical neurons (Wilson 1995). However, one of the main electrophysiological features of SONs that has been recorded in vivo is a low level of spontaneous firing (Wilson 1995;Charpier et al. 1999). It is now assumed that this weak excitability of SONs is due to nonlinear electrical membrane properties rather than to a mutual synaptic inhibition (Jaeger et al. 1994;Nisenbaum et al. 1994;Nisenbaum and Wilson 1995;Wilson 1995). The nonlinear properties of SONs result from a set of voltage-gated potassium and sodium currents, including an inwardly rectifying potassium current (I Kir ), a fast (I Af ), a slowly inactivating Acurrent (I As ), a persistent (I Krp ) potassium current, a slowly inactivating (I NaS ), and a persistent (I NaP ) sodium current (Hoehn et al. 1993;Nisenbaum et al. 1994;Chao and Alzheimer 1995;Nisenbaum and Wilson 1995;Nisenbaum et al. 1996;Gabel and Nisenbaum 1998;Nisenbaum et al. 1998). A distinctive voltage behavior of SONs is conferred by I As , which is responsible for a slowing of the rate of depolarization that is evident from membrane potentials near −60 mV Nisenbaum et al. 1994;Gabel and Nisenbaum 1998). When a depolarizing input is maintained, the slow ramp of depolarization in SONs can lead to a long latency of action potential discharge (Fig. 1A, part 1, crossed arrow; Nisenbaum et al. 1994).Recently, using in vivo intracellular recordings from anesthetized rats, we have investigated the role of intrinsic electrical properties of SONs in the temporal integration of their cortical synaptic inputs (Mahon et al. 2000). We showed that direct activation of SONs through intracellular injection of a depolarizing current pulse induced a shortterm (Յ1 sec) increase in their membrane excitability. This change in excitability facilitated the ability of corticostriatal excitatory postsynaptic potentials (EPSPs) to induce firing. In this study we attempted to specify the mechanisms involved in the use-dependent increase in SON excitability. To this end, we have now perfor...

NMDA/AMPA Ratio Impacts State Transitions and Entrainment to Oscillations in a Computational Model of the Nucleus Accumbens Medium Spiny Projection Neuron

“…The effect of inward and outward rectifying potassium currents on both the synaptic input and the electrotonic properties of MSP dendrites with spines have been extensively studied (Wilson, 1992(Wilson, , 1995. Our results are in agreement with previous experimental and modeling results on the role of K IR and K A currents in determining up and down states (Wilson and Kawaguchi, 1996;Gruber et al, 2003) and the importance of the inactivation of K As in the ramp to first spike (Nisenbaum et al, 1994;Mahon et al, 2000).…”

“…Simulations were performed on an Apple Computers (Cupertino, CA) dual 2.5 GHz Power Macintosh G5 or in parallel on a 12-node cluster with dual 2.8 GHz processors per node (Penguin Computing, San Francisco, CA). The model presented here extends previous MSP models in several ways (Wilson, 1995;Mahon et al, 2000;Kitano et al, 2002;Gruber et al, 2003;Wood et al, 2004). Notably, this is the first MSP model to individually include all reported species of calcium and calcium-dependent potassium currents as well as recently updated parameters for several potassium currents.…”

Gating Information by Two-State Membrane Potential Fluctuations

“…We tested this by constructing another biophysical model based on ionic currents measured from medium spiny neurons in the striatum. These neurons have an extensive repertoire of potassium currents that have been well characterized (Mahon et al 2000;Nisenbaum and Wilson 1995;Wolf et al 2005) and exhibit two-state membrane potential fluctuations (O'Donnell and Grace 1995;Plenz and Aertsen 1996;Wilson 1993). We included the fast and slow A-like potassium currents (Nisenbaum and Wilson 1995), an inward rectifier current (Nisenbaum and Wilson 1995), an L-type calcium current (Churchill and Macvicar 1998), and a persistent sodium current in a three-compartment model of a medium spiny neuron (see supplementary information for details).…”

Learning intrinsic excitability in medium spiny neurons

“…Parameters for slow A-type K channels ( I As ) were adapted from 23, 24 , for fast A-type K channels ( I Af ) from 25 , for inward rectifying K channels ( I Kir ) from 26 , and the resulting parameter tables were compared with 27 and 28 , see Table 2.…”