Much of the physiology of the last 25 years has shifted from a focus on the single channel or single cell to ensembles or circuits, in search of patterns of activity that link to behavior. Recording has been expanded to ensembles of neurons, and calcium-imaging dyes or voltage-sensitive dyes are now used to monitor the activity of hundreds of neurons over time to begin to map how and where information is processed. Most recently, the capture of simultaneous, buy Ion Channel Ligand Library real-time activity of over 80% of the neurons in the larval zebrafish brain with lightsheet microscopy suggests patterns of large-scale activity that had not

been foreseen by recording individual or even small groups of neurons ( Ahrens et al., 2013). The macroconnectome now being developed promises to provide a reference atlas of the wiring diagram of the human brain, much as the genome project provided a reference atlas of DNA

sequence (http://www.humanconnectome.org). Beyond better descriptions of connections and circuitry, tools like optogenetics (Tye and Deisseroth, 2012) and DREADDs (Nawaratne et al., 2008) have provided neuroscientists with the ability to manipulate sets of cells in circuits to test specific causal questions about circuit and network anatomy, connectivity, and function. Who could have imagined in 1988 the broad use of tools, based on advances BMN 673 solubility dmso in molecular and cellular neuroscience, for precise Thymidine kinase control over circuits in awake, behaving animals? As a result, we can now begin to understand ongoing activity patterns that are overlaid

on anatomical structure and to study how experience alters circuit function. For some invertebrate circuits, the entire network has been specified and elegantly modeled (Bargmann and Marder, 2013). These studies make clear that although form and function are related, knowing the microanatomy of connections is not sufficient to understand the function of a simple circuit. We are just beginning to understand the principles of brain organization that are essential for information encoding, storage, manipulation, and retrieval. Indeed, understanding the stages and processes of manipulation of information within neural networks will be the next major challenge for neuroscience. The extraordinary progress in neuroscience over the past two decades may, in retrospect, look like the unprecedented two-decade period in physics just a century ago. New tools and new concepts have transformed the way we think about the brain and its constituent parts, a transformation that has been chronicled faithfully in Neuron, monthly beginning in 1988 and bimonthly beginning in 2001, as the journal, responding to the evolution of the field, expanded its scope beyond the original mandate of molecular and cellular neuroscience.