Great Expectations

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Science  16 Oct 2009:
Vol. 326, Issue 5951, pp. 339
DOI: 10.1126/science.1182101

A convergence of diverse disciplines is fueling the expansion of neuroscience research, and underpinning this growth are increasingly advanced technologies such as high-performance computation, simulation and neuron modeling, real-time and high-resolution brain imaging, advanced recording techniques, and detailed neuron mapping. This special issue of Science gives a well-deserved nod to the technological innovations that have improved our understanding of the development, function, and disorders of the nervous system, and that will continue to open up many new questions about the human brain.

Today, there are many state-of-the-art institutions worldwide that focus on brain and cognitive science, helping to bridge the gaps between different knowledge bases, such as those centered on genomic information or brain images. Ten years after its establishment in 1997, the RIKEN Brain Science Institute reorganized to establish an Advanced Technology Development Core, designed to create new methods for studying the brain. Our efforts will hopefully speed the progress of neuroscience as we address the growing needs of this field. For example, more robust means are needed to characterize brain signals in ways that will enhance the ability to monitor neural processes. There is also a need for tools that detect the dynamic organization and coordinated activity of populations of neurons in the brain, so as to explore their relevance to behavior and cognition. And we want to approach information processing through new mathematical tools, to better understand how ensembles of neurons process information and consequently modify their structures as the brain learns. As well, genetic engineering approaches must be further refined if we are to analyze the neuronal circuits that underlie complex conditions such as mental disorders.

One approach that is becoming increasingly important combines optical and molecular genetic methods. These “optogenetic” technologies facilitate the discovery of mechanisms by which neurons process and integrate synaptic inputs. Genetically encoded sensors, constructed by fusing fluorescent proteins to functional proteins involved in physiological signaling, now allow the use of light to image excitable cell activity in large sets of neurons. These sensors can be introduced into neurons selectively, and they extract neuronal signals from an intact brain more efficiently than can organic dyes. By limiting the expression of a sensor to a subpopulation of neurons, one can visualize the connectivity between multiple different neuron groups and examine how the activity of specific neurons contributes to the function of neural circuits. Different sensors have thus far been developed to investigate signal integration, synaptic transmission, and neuronal plasticity; we're only in the very early stages of exploiting this method to its full potential.


Ultimately, we want to understand brain function in a physiological context. In this regard, a key approach to complement these combined optical-genetic methods involves generating animals to which two-photon excitation microscopy can be applied. This microscopic approach has markedly increased penetration into tissue, and it is being widely used to view the intact brain. Because of recent progress in gene transfer techniques, including virus-mediated gene transfer and germline transmission of transgenes, the experimental animals to be studied are not limited to mice and can be extended to nonhuman primates.

In addition, these new genetically encoded tools are likely to spark an evolution in microscopy. For example, advances in brain imaging have enabled scientists to use miniaturized fluorescence microscopes based on fiber optics to observe brain activity in awake behaving animals. A new microscopy system will also be needed for the large-scale reconstruction of neuronal circuits in brain samples, because one major goal of the neuroscience community is to create a complete physical map of the human nervous system. Soon we may be admiring sweeping views of axons and dendrites as they carry signals that travel long distances.

Our expectations for neuroscience discovery remain high. With technologies continually improving, why shouldn't they be?

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