Overcoming this divide represents perhaps the greatest challenge in the neurosciences. Acknowledgments This work was supported by grants from the National institute on Drug Abuse. Selected abbreviations and acronyms Nac nucleus accumbens CREB cAMP response element binding protein ΔFosB a Fos family transcription factor VTA

ventral tegmental area AMPA Inhibitors,research,lifescience,medical α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid LTD long-term depression LTP long-term protentiation BDNF brain-derived neurotrophic factor NKkB nuclear factor kB
Working memory is, essentially, what we think of as thought. It is our mental sketchpad, where we hold information “in mind” and Inhibitors,research,lifescience,medical process it. Naturally, it has garnered much I BET 762 empirical interest, and this has yielded a robust and commonly reported neural correlate: sustained neural activity. Sustained activity can be seen when humans and animals are performing tasks thought to engage working memory. Delayed response tasks, for example, include a short gap in time (seconds) between a sensory cue and the opportunity to act based on that cue. Higher cortical areas, especially the prefrontal cortex (PFC), the putative “executive” cortex, show elevated levels of neural activity over that delay, as if the neurons

Inhibitors,research,lifescience,medical are bridging the gap by sustaining their firing to cue. Because short-term buffering of information in an active “online” state is a keystone of working Inhibitors,research,lifescience,medical memory, sustained delay activity has become virtually

synonymous with “working memory,” at least to neuroscientists. However, it is important to keep in mind that Baddeley’s original working memory model Inhibitors,research,lifescience,medical was meant to be a model of cognition and that there is more to thought than short-term memory (Figure 1).1 Imagine planning a simple errand. You do not just hold elements of the plans in mind; you weigh alternatives, make decisions, and order the thoughts until you think the plan achieves your objectives. In short, there is more to working memory than “memory”; there is also the “working.” Indeed, what sets working memory apart from mere short-term storage and elevates it to a model of cognition writ large is the inclusion of a “central executive” (Figure 1), a set of mechanisms that together act to manage and regulate what we hold “in mind” (ie, contents of the Ribonucleotide reductase short-term memory buffers). These executive functions are less well understood because they are less tractable than short-term buffering of information. But we have made progress. Here, we review work on the neural correlates of working memory and suggest candidate mechanisms. Figure 1. Baddeley’s working memory model. This includes short-term memory buffers (visuospatial and phonological loops) under the control of a central executive.