05 two-tailed; Figure 5E). These findings suggest that GABAA-mediated inhibition contributes to the suppression of fimbria-evoked EPSPs following the PFC train but does not account entirely for this suppression. We found that high-frequency PFC stimulation suppresses EPSPs arising from single-pulse fimbria stimulation in VS MSNs. This suppression

was observed at a short latency following the PFC Depsipeptide nmr stimulus (50 ms after the final pulse in a 10 pulse, 50 Hz train delivered to the PFC), but not at a long latency (500 ms) following the PFC train. The suppression of fimbria-evoked EPSPs by the PFC cannot be attributed solely to the depolarization of recorded cells elicited by the PFC train, as fimbria-evoked EPSPs were not attenuated by the depolarization elicited by spontaneous up states or current

injection through the recording electrode. Moreover, burst-like activation of the PFC was necessary to produce suppression of fimbria responses; single-pulse stimulation of the PFC did not reduce the magnitude of the fimbria-evoked EPSP. The suppression of glutamatergic responses by robust PFC activation extended to other afferents as well, as PFC train stimulation attenuated thalamus-evoked responses. Trains of stimuli to the HP did not attenuate PFC-evoked EPSPs, consistent with the proposed gating relationship of the HP with VS MSNs (O’Donnell and Grace, 1995). However, burst-like stimulation of the thalamus was able to attenuate the PFC-evoked response, but this effect was not as dramatic as the near-total suppression of HP and thalamic inputs caused by PFC train stimuli. These check details data suggest that burst-like PFC activity elicits brief heterosynaptic suppression of HP and thalamic Adenosine inputs to the VS. The integration of excitatory inputs in the VS is complex, with several nonlinearities (Goto and O’Donnell, 2002; Wolf et al., 2009). HP afferents are critical for the spontaneous up states observed in anesthetized animals; VS up states are eliminated if the fimbria/fornix is transected or inactivated (O’Donnell

and Grace, 1995) and can be detected simultaneously with HP spindles (Goto and O’Donnell, 2001b). As MSNs fire action potentials only from the up state, the relationship of the HP to the VS has been described as a gating mechanism, in which the VS must receive convergent excitatory input from the HP for other excitatory inputs, including those from the PFC, to be transmitted onward to downstream targets (O’Donnell and Grace, 1995). The critical role of the HP in shaping VS activity is also apparent in the behaving animal. Under resting conditions, the VS shows highly synchronous field potential activity with the ventral HP (Gruber et al., 2009a). Furthermore, place cells are found in the VS (Lavoie and Mizumori, 1994), and their activity is likely driven by HP inputs.