It will be interesting to identify other neurovascular structures in which this model applies, both in peripheral tissues and also in the brain, where neurons are also
intimately associated with blood vessels but the mechanism underlying it is completely unknown. “
“Replay of exploration-associated hippocampal activity during rest is an important aspect of spatial learning (Davidson et al., 2009, Karlsson Sirolimus and Frank, 2009 and Skaggs and McNaughton, 1996). The hippocampus contains neurons that are active at specific spots in a maze animals are trained to navigate, and these neurons have been termed “place cells” (O’Keefe and Dostrovsky, 1971). Place cells are thought to encode spatial location and the overall pattern of hippocampal neural ensembles may therefore be encoding cues used to navigate. Several groups have provided evidence that replay of neural ensemble activity during sleep or quiet awake states is critical for memory consolidation and allows navigating using spatial cues (Euston et al., 2007). Reactivation of neural activity associated with behavioral sequences has been shown to be more than simple recall of recent experience. Neural replay includes patterns of activity associated with all possible trajectories during the learned navigation task (Gupta et al.,
2010), suggesting Mdm2 inhibitor that replay is a critical physiological element in high-order cognitive processes. This is perhaps one of the highest-order cognitive physiological mechanisms unveiled in rodents, as it relates to more than memory but to pondering of different scenarios evaluated in the learning process. The composition of active and
replayed neural ensembles can take a large number of possible combinations, conferring a relatively small circuit such as the hippocampus STK38 with the necessary flexibility to learn in a changing environment, a feat virtually impossible with hardwired connections. The selection and reactivation of neural ensembles is perhaps the simplest solution for such a complex behavioral need. One could speculate that ensemble coding, with the large number of combinations of neural activity and their replay after experience, is a common mechanism for many, if not all, learning processes in the brain and not necessarily limited to spatial learning. If this is the case, replay could be an ideal measure to identify altered function in brains with manipulations intended to model disorders with cognitive impairment, such as schizophrenia. To better understand the neural underpinnings of altered cognition it is critical to explore the impact of manipulations of schizophrenia-related genes in rodent models. In this issue of Neuron, Suh et al. (2013) show enhanced firing and increased ripple activity during replay in the hippocampus of calcineurin knockout (KO) mice. These mice target a gene associated with risk for schizophrenia ( Gerber et al.
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