Intrinsic persistent spiking mechanisms in medial entorhinal cortex (mEC) neurons may play a role in active maintenance of working memory. However, electrophysiological studies of rat mEC units have primarily focused on spatial modulation. We sought evidence of differential spike rates in the mEC in rats trained on a T-maze, cued spatial delayed response task. Animals begin at the base of the T-maze where a 1-sec white noise and visual light cue are presented on the left or right side of the maze. Rats are rewarded for responding toward the cued direction. In correct trials, we observed decreased spike rates during the delay period, the time interval between cue presentation and reward delivery. Firing-rate histograms show significant decreases during the delay period compared to 5-sec windows from both pre-cue and post-reward periods. We analyzed how running speed and trajectory specificity correlated to spike rate. Twice as many cells were responsive to cue alone compared to running speed. Trajectory specificity did not relate significantly to firing rate. Decreased spike rate may reflect active maintenance in other structures inhibiting mEC. Alternately, the reduction may reflect decreases in background activity during enhanced attention and cholinergic modulation. Lastly, animals often ran through the T-maze choice-point with varying speed. We calculated the spatial posterior probability density from spike rates during these choice-point passes. Slow passes through the choice point were characterized by greater probability of decoding to the reward locations on correct trials compared to quick passes on the maze consistent with similar "look-ahead" properties previously reported in the hippocampus and ventral striatum.[Supplemental material is available for this article.]Multiple memory systems play a role in decision-making mechanisms in animals performing behavioral tasks. Of these systems, working memory provides a temporary store for information during performance of cognitive tasks (Baddeley and Wilson 2002;Hasselmo and Stern 2006). Previous studies in animals suggest that localized networks in the prefrontal cortex perform active maintenance of neural activity representing familiar stimuli in delayed-match-to-sample tasks (Fuster 1973), cued-choice behavior (Fujisawa et al. 2008), and object recognition (Asaad et al. 1998). However, parahippocampal structures have also been implicated as a buffer for working memory in rodents and primates (Hasselmo and Stern 2006). Unit recording has demonstrated entorhinal neurons that fire during the delay period of delayedmatch-to-sample tasks in rats (Young et al. 1997) and monkeys (Suzuki et al. 1997).Intracellular recording from in vitro slice preparations of rat medial entorhinal cortex (mEC) demonstrates neurons that persistently spike after a single depolarization during pharmacological activation of acetylcholine receptors (Klink and Alonso 1997;Egorov et al. 2002;Yoshida et al. 2008). Several computational models have demonstrated how these intrinsic mechani...

Prior studies of head direction (HD) cells indicate strong landmark control over the preferred firing direction of these cells, with few studies exhibiting shifts away from local reference frames over time. We recorded spiking activity of grid and HD cells in the medial entorhinal cortex of rats, testing correlations of local environmental cues with the spatial tuning curves of these cells' firing fields as animals performed continuous spatial alternation on a T-maze that shared the boundaries of an open-field arena. The environment was rotated into configurations the animal had either seen or not seen in the past recording week. Tuning curves of both cell types demonstrated commensurate shifts of tuning with T-maze rotations during less recent rotations, more so than recent rotations. This strongly suggests that animals are shifting their reference frame away from the local environmental cues over time, learning to use a different reference frame more likely reliant on distal or idiothetic cues. In addition, grid fields demonstrated varying levels of "fragmentation" on the T-maze. The propensity for fragmentation does not depend on grid spacing and grid score, nor animal trajectory, indicating the cognitive treatment of environmental subcompartments is likely driven by task demands.