When utilizing the rabies virus as a traditional retrograde tracer, virus particles

find more are injected at high titer into the brain region of interest, spread through the extracellular space, and are then taken up at axon terminals (Figure 7F, top). We noted not only a large absolute number of labeled neurons in the SNc using this method (Figures 7D and 7E), but also that the proportion of labeled SNc cells compared to the total number of labeled neurons in the brain was much higher than observed using the monosynaptic rabies virus. Our data indicated that 7.6% ± 0.3% (mean ± SEM, n = 5) of the total input neurons labeled in the brain using this assay arose from SNc (Figure 7F, bottom). These values very closely mirror the estimated proportion of labeled neurons in SNc using other retrograde tracers (Pan et al., 2010), as well as the overall proportion of dopaminergic axon terminals in striatum previously determined through EM (Groves et al., 1994). This indicates that rabies virus is very efficiently taken up at dopaminergic axon terminals, suggesting that monosynaptic

spread of rabies virus from direct- or indirect-pathway MSNs is limited by some other factor (see Discussion). Furthermore, the similar amount of synaptic input to direct versus indirect-pathway MSNs indicates that differential http://www.selleckchem.com/products/Vorinostat-saha.html dopamine signaling in MSN subtypes does not arise from differences in anatomical connectivity. The dorsal raphe nuclei provided some synaptic input to both pathways (1.1% ±

0.8% in D1R-Cre mice, 0.1% ± 0.1% in D2R-Cre mice) but the total number of synaptic inputs was relatively small. The small amount of serotonergic input again suggests that neuromodulatory streams may provide relatively little direct synaptic input to striatal MSNs. However, the small total number of counted inputs, combined with high variability in labeling, prevented a direct statistical comparison between synaptic and total serotonergic input. Direct serotonergic input to the dorsal striatum has been previously described (Pan et al., 2010 and Vertes, 1991), but its potential functional roles are only beginning not to be explored (Di Matteo et al., 2008). Minor inputs (<1% of total inputs, but documented in at least three animals), were also documented from the pedunculopontine tegmental nucleus (PPTg), subthalamic nucleus, hypothalamus, and basal nucleus of Meynert. The projection from PPTg to the dorsal striatum has been described in other animal models (Nakano et al., 1990 and Saper and Loewy, 1982), suggesting that PPTg to dorsal striatum connectivity is highly conserved across species. The subthalamic nucleus has also been shown to provide some direct input to dorsal striatum in mice (Pan et al., 2010), indicating high levels of interconnectivity between mouse basal ganglia nuclei.