, 1994). However, synchrony across large populations of MSNs is rarely seen in healthy individuals and, rather, is a hallmark of striatal dysfunction in motor diseases such as PD and dystonia (Buzsáki et al., 1990, Costa et al., 2006, Gernert et al., 2002, Hammond et al., 2007, Hutchison et al., 2004 and Kühn et al., 2008). In particular, dopamine depletion is associated with increased network oscillations in the β frequency band that may occlude normal signal propagation through the basal ganglia (Brown, 2003,

Kühn et al., 2004 and Mallet et al., 2008b). Although pathological β oscillations after dopamine depletion are a feature of the entire basal ganglia network, some of the most striking shifts in neuronal-firing patterns check details occur in the GP and STN (Bevan et al., 2002, Mallet et al., 2008a and Terman et al.,

2002). These nuclei become highly coupled in an oscillatory pattern after dopamine depletion, and disruption of this abnormal synchrony with deep brain stimulation is an effective therapeutic treatment in patients with PD (Bevan et al., 2002 and Hammond et al., 2007). Although GP neurons do not show a substantial change in average firing rate after dopamine depletion, they do show changes in firing pattern, shifting to a synchronized, bursting mode of firing in resting animals or patients with PD (Brown et al., 2001 and Raz et al., 2000). In part, this altered firing pattern may depend on increased synchronous inhibition from striatal D2 MSNs (Terman et al., 2002). However, a number of other changes in the striatum BAY 73-4506 ic50 have been described after dopamine depletion that could alter the Adenosine output of D2 MSNs. These include

changes in LTD and LTP at excitatory inputs in MSNs (Calabresi et al., 2007, Kreitzer and Malenka, 2008, Lovinger, 2010 and Shen et al., 2008), decreased spine density and loss of glutamatergic synapses onto D2 MSNs (Day et al., 2008), changes in cholinergic signaling (Ding et al., 2006), and changes in a non-FS population of GABAergic interneurons (Dehorter et al., 2009). In this study, we use a simple model of the striatal circuit to demonstrate that experimentally increased innervation of D2 MSNs by FS interneurons may be sufficient to enhance synchrony of D2 MSNs. This, along with other changes in striatal circuitry, could enhance D2 MSN regulation of downstream target neurons and contribute to increased synchrony in the GP and the STN (Burkhardt et al., 2007, Costa et al., 2006, Terman et al., 2002 and Walters et al., 2007). Furthermore, because a subset of GP neurons projects back to striatal interneurons (Bevan et al., 1998 and Gage et al., 2010), this may also amplify indirect-pathway synchrony in the striatum, leading to robust pathological oscillations in the indirect-pathway basal ganglia circuit. Coronal sections containing dorsal striatum were prepared in cold sucrose cutting solution: 79 mM NaCl, 23 mM NaHCO3, 68 mM sucrose, 12 mM glucose, 2.3 mM KCl, 1.1 mM NaH2PO4, 6 mM MgCl2, and 0.5 mM CaCl2.