, 2005), and decision-making epochs are characterized by high-frequency oscillations in the gamma range (30–50 Hz). Robust, burst-like activation of the PFC reliably Torin 1 produces up states in VS MSNs (Gruber and O’Donnell, 2009). Furthermore, during behavioral epochs marked by high-frequency oscillations and burst firing in the PFC, the synchrony typically observed between the VS and the HP as coherent theta oscillations is lost in favor of a period of VS entrainment to the PFC (Gruber et al., 2009a). These findings suggest that the PFC is capable of disengaging

the VS from the HP; thus, one excitatory projection can somewhat paradoxically reduce the efficacy of another glutamatergic input in VS MSNs. Although input integration is typically additive for excitatory projections, competition among converging inputs can also occur. For example, in hippocampal slices, one set of inputs to CA1 neurons may reduce the

efficacy of another (Alger et al., 1978; Lynch et al., 1977), and in the PFC, similar interactions between cortical and thalamic inputs have been reported (Fuentealba et al., 2004). Here, we tested whether brief, robust PFC activation disengages the VS from ongoing HP activity by way of heterosynaptic suppression in VS MSNs using in vivo intracellular recordings. We performed in vivo intracellular recordings in 47 check details neurons from 36 adult male rats using standard recording conditions and 22 neurons from 15 rats using electrodes containing the GABAA antagonist picrotoxin. A subset of these cells (n = 10) were processed for Neurobiotin labeling and were morphologically identified as MSNs (Figure 1A). All neurons included in this study were located within the striatal region receiving afferents from the medial PFC and HP (Voorn et al., 2004), including the nucleus accumbens core and the ventral aspect of the dorsomedial striatum (Figure 1B). All recorded cells exhibited spontaneous transitions between negative resting membrane potentials (down states; −84.1 ± 8.1 mV, mean ± SD) and depolarized up states (−70.9 ± 7.2 mV) closer to action potential threshold (Figure 1C). Up states else occurred at a frequency of 0.6 ± 0.2 Hz with a duration

of 521.8 ± 180.8 ms. The majority of recorded neurons were silent (29/47; 62%), but spontaneous firing was detected in the remaining 18 neurons at 0.96 ± 1.4 Hz (range, 0.01–5.2 Hz). Action potentials (spontaneous or evoked) in all neurons had an amplitude of 52.8 ± 7.9 mV from threshold. Input resistance in the down state was 54.5 ± 17.4 MΩ. These properties are similar to what has been previously reported in VS MSNs (Brady and O’Donnell, 2004; Goto and O’Donnell, 2001a, 2001b; O’Donnell and Grace, 1995). To assess whether robust PFC activation suppresses MSN responses to HP afferents, stimulating electrodes were targeted to the medial PFC and the fimbria-fornix, the fiber bundle carrying HP inputs to the VS (n = 21 neurons; Figure 1D).