John Bladon

It is commonly conceived that the cortical areas of the hippocampal region are functionally divided into the perirhinal cortex (PRC) and the lateral entorhinal cortex (LEC), which selectively process object information; and the medial entorhinal cortex (MEC), which selectively processes spatial information. Contrary to this notion, in rats performing a task that demands both object and spatial information processing, single neurons in PRC, LEC, and MEC, including those in both superficial and deep cortical areas and in grid, border, and head direction cells of MEC, have a highly similar range of selectivity to object and spatial dimensions of the task. By contrast, representational similarity analysis of population activity reveals a key distinction in the organization of information in these areas, such that PRC and LEC populations prioritize object over location information, whereas MEC populations prioritize location over object information. These findings bring to the hippocampal system a growing emphasis on population analyses as a powerful tool for characterizing neural representations supporting cognition and memory. SIGNIFICANCE STATEMENT: Contrary to the common view that brain regions in the "what" and "where" streams distinctly process object and spatial cues, respectively, we found that both streams encode both object and spatial information but distinctly organize memories for objects and space. Specifically, perirhinal cortex and lateral entorhinal cortex represent objects and, within the object-specific representations, the locations where they occur. Conversely, medial entorhinal cortex represents relevant locations and, within those spatial representations, the objects that occupy them. Furthermore, these findings reach beyond simple notions of perirhinal cortex and lateral entorhinal cortex neurons as object detectors and MEC neurons as position detectors, and point to a more complex organization of memory representations within the medial temporal lobe system.

Extracorporeal photopheresis (ECP) is used in the treatment of T-cell-mediated disorders. However, the mechanism by which ECP achieves its effect remains illusive. Over recent years the ability of ECP to induce apoptosis has been demonstrated by cell culture experiments and retrospective histological analysis. We investigated if apoptosis could be determined in samples tested ex vivo from the UVAR:ECP system. Lymphocytes from 11 patients (six with cutaneous T-cell lymphoma, four with graft-versus-host disease, and one with scleredema) were isolated at three stages of the ECP process: immediately before ECP treatment, from the first buffy coat collected, and post UV irradiation, prior to re-infusion. Using flow cytometry each stage was tested for the early apoptotic markers; Annexin V, ApoptestTM and Carboxy-SNARF-1-AM. Comparisons of the pre-ECP and pre-infusion samples demonstrated a significant increase in apoptotic lymphocytes for all three flow cytometric techniques (P < 0.01). Increases between the pre-ECP and first buffy coat, used as a measure of the extracorporeal manipulation, were much lower. These results demonstrate that ECP directly induces significant levels of apoptosis in lymphocytes of CTCL, GvHD and scleredema patients. The apoptosis of these lymphocytes may contribute to the ECP effect.

Episodic memory binds the spatial and temporal relationships between the elements of experience. The hippocampus encodes space through place cells that fire at specific spatial locations. Similarly, time cells fire sequentially at specific time points within a temporally organized experience. Recent studies in rodents, monkeys, and humans have identified time cells with discrete firing fields and cells with monotonically changing activity in supporting the temporal organization of events across multiple timescales. Using in vivo electrophysiological tetrode recordings, we simultaneously recorded neurons from the prefrontal cortex and dorsal CA1 of the hippocampus while rats performed a delayed match to sample task. During the treadmill mnemonic delay, hippocampal time cells exhibited sparser firing fields with decreasing resolution over time, consistent with previous results. In comparison, temporally modulated cells in the prefrontal cortex showed more monotonically changing firing rates, ramping up or decaying with the passage of time, and exhibited greater temporal precision for Bayesian decoding of time at long time lags. These time cells show exquisite temporal resolution both in their firing fields and in the fine timing of spikes relative to the phase of theta oscillations. Here, we report evidence of theta phase precession in both the prefrontal cortex and hippocampus during the temporal delay, however, hippocampal cells exhibited steeper phase precession slopes and more punctate time fields. To disentangle whether time cell activity reflects elapsed time or distance traveled, we varied the treadmill running speed on each trial. While many neurons contained multiplexed representations of time and distance, both regions were more strongly influenced by time than distance. Overall, these results demonstrate the flexible integration of spatiotemporal dimensions and reveal complementary representations of time in the prefrontal cortex and hippocampus in supporting memory-guided behavior.