Dissecting Inhibitory Control of Striatal Projection Neurons

The striatum is the main input nucleus of the basal ganglia and is involved in processing inputs from the cortex and thalamus. This processing is carried out by GABAergic medium spiny projection neurons (MSPN) that comprise 90-95% of the neuronal population in the rodent striatum (Bolam and Bennett, 1993). These neurons project to the basal ganglia output structures, the globus pallidus and substantia nigra; therefore understanding striatal processing will help elucidate further the factors affecting basal ganglia function.

GABAergic inhibition plays a very important role in the modulation of the MSPN network (Tepper et al., 2008). Among the different GABAergic interneurons in the striatum, the fast-spiking interneurons (FSIs) provide strong feedforward inhibition of the MSPNs (Koos & Tepper, 1999; Tepper et al., 2008), whereas MSPNs provide widespsread but weak feedback inhibition of each other. The FSIs are interconnected through electrical synapses/gap junctions (Galarreta and Hestrin, 2001) and GABAergic synapses (Gittis et al., 2010). It has been hypothesized that gap junctions are involved in coordinating synchronous activity in populations of the MSPN network (Berke et al., 2004, Galarreta and Hestrin, 2002). However, recent experiments (Berke, 2008) suggest that FSIs do not fire synchronously, and recent simulations (Hjorth et al., 2009) have shown that gap junctions alone are not sufficient to synchronize FSI network activity in the striatum, except transiently in response to synchronous cortical activity. The function of the widespread but weak feedback loop of the MSPNs is also not clear (Plenz, 2002).

The present study constructs a network of the realistic multi-compartmental model MSPNs receiving both realistic synaptic input from a model FSI network and simulated input trains from the cortex. The FSI network, which also receives cortical input trains, is connected by both gap junctions (Hjorth et al., 2009) and chemical synapses (Gittis et al., 2010). The simulations address the role of chemical synapses and gap junctions in the FSI network in controlling activity in the MSPN network of the striatum. The simulations also parse out the contributions of the feedforward and feedback connections on the MSN output thus addressing the functional contribution of each type of connection to the network activity.