http://www.culturacientifica.org/textosudc/neurogenesis/adult_neurogenesis.pdf

Adult neurogenesis in the mammalian brain: significant answers and significant questions.

Optogenetics in neural systems.

Genetically encoded, single-component optogenetic tools have made a significant impact on neuroscience, enabling specific modulation of selected cells within complex neural tissues. As the optogenetic toolbox contents grow and diversify, the opportunities for neuroscience continue to grow. In this review, we outline the development of currently available single-component optogenetic tools and summarize the application of various optogenetic tools in diverse model organisms.

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The Development and Application of Optogenetics

Human learning is a complex phenomenon requiring flexibility to adapt existing brain function and precision in selecting new neurophysiological activities to drive desired behavior. These two attributes—flexibility and selection—must operate over multiple temporal scales as performance of a skill changes from being slow and challenging to being fast and automatic. Such selective adaptability is naturally provided by modular structure, which plays a critical role in evolution, development, and optimal network function. Using functional connectivity measurements of brain activity acquired from initial training through mastery of a simple motor skill, we investigate the role of modularity in human learning by identifying dynamic changes of modular organization spanning multiple temporal scales. Our results indicate that flexibility, which we measure by the allegiance of nodes to modules, in one experimental session predicts the relative amount of learning in a future session. We also develop a general statistical framework for the identification of modular architectures in evolving systems, which is broadly applicable to disciplines where network adaptability is crucial to the understanding of system performance.

/pdf/dynamic-reconfiguration-of-human-brain-networks-during-44uymtqkvg.pdf

Dynamic reconfiguration of human brain networks during learning.

Our understanding of the cellular implementation of systems-level neural processes like action, thought and emotion has been limited by the availability of tools to interrogate specific classes of neural cells within intact, living brain tissue. Here we identify and develop an archaeal light-driven chloride pump (NpHR) from Natronomonas pharaonis for temporally precise optical inhibition of neural activity. NpHR allows either knockout of single action potentials, or sustained blockade of spiking. NpHR is compatible with ChR2, the previous optical excitation technology we have described, in that the two opposing probes operate at similar light powers but with well-separated action spectra. NpHR, like ChR2, functions in mammals without exogenous cofactors, and the two probes can be integrated with calcium imaging in mammalian brain tissue for bidirectional optical modulation and readout of neural activity. Likewise, NpHR and ChR2 can be targeted together to Caenorhabditis elegans muscle and cholinergic motor neurons to control locomotion bidirectionally. NpHR and ChR2 form a complete system for multimodal, high-speed, genetically targeted, all-optical interrogation of living neural circuits.

Multimodal fast optical interrogation of neural circuitry

Elucidation of the neural substrates underlying complex animal behaviors depends on precise activity control tools, as well as compatible readout methods. Recent developments in optogenetics have addressed this need, opening up new possibilities for systems neuroscience. Interrogation of even deep neural circuits can be conducted by directly probing the necessity and sufficiency of defined circuit elements with millisecond-scale, cell type-specific optical perturbations, coupled with suitable readouts such as electrophysiology, optical circuit dynamics measures and freely moving behavior in mammals. Here we collect in detail our strategies for delivering microbial opsin genes to deep mammalian brain structures in vivo, along with protocols for integrating the resulting optical control with compatible readouts (electrophysiological, optical and behavioral). The procedures described here, from initial virus preparation to systems-level functional readout, can be completed within 4–5 weeks. Together, these methods may help in providing circuit-level insight into the dynamics underlying complex mammalian behaviors in health and disease.

/pdf/optogenetic-interrogation-of-neural-circuits-technology-for-4963rri6tu.pdf

Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures.

Despite a rapidly-growing scientific and clinical brain imaging literature based on functional magnetic resonance imaging (fMRI) using blood oxygenation level-dependent (BOLD) signals, it remains controversial whether BOLD signals in a particular region can be caused by activation of local excitatory neurons. This difficult question is central to the interpretation and utility of BOLD, with major significance for fMRI studies in basic research and clinical applications. Using a novel integrated technology unifying optogenetic control of inputs with high-field fMRI signal readouts, we show here that specific stimulation of local CaMKIIalpha-expressing excitatory neurons, either in the neocortex or thalamus, elicits positive BOLD signals at the stimulus location with classical kinetics. We also show that optogenetic fMRI (of MRI) allows visualization of the causal effects of specific cell types defined not only by genetic identity and cell body location, but also by axonal projection target. Finally, we show that of MRI within the living and intact mammalian brain reveals BOLD signals in downstream targets distant from the stimulus, indicating that this approach can be used to map the global effects of controlling a local cell population. In this respect, unlike both conventional fMRI studies based on correlations and fMRI with electrical stimulation that will also directly drive afferent and nearby axons, this of MRI approach provides causal information about the global circuits recruited by defined local neuronal activity patterns. Together these findings provide an empirical foundation for the widely-used fMRI BOLD signal, and the features of of MRI define a potent tool that may be suitable for functional circuit analysis as well as global phenotyping of dysfunctional circuitry.

Global and local fMRI signals driven by neurons defined optogenetically by type and wiring

/pdf/optogenetic-interrogation-of-neural-circuits-technology-for-39snvmp1op.pdf

Optogenetic interrogation of neural circuits: technology for probing mammalian brain

Replying to N. K. Logothetis , 10.1038/nature09532 (2010)
 This is a welcome opportunity to discuss ofMRI, a technology for testing the causal and global impact of defined cell populations in vivo1. The accompanying Comment2 reviews well-known neuroanatomy, but does seem, in its entirety, to be founded on a suggestion that, after experiments were conducted to drive a defined circuit element and measure resulting BOLD signals1, we concluded that no other contributory circuit element was recruited by the driven population. This was not the case, however, as correctly understood by others in the fMRI community3,4,5 and as explained in the paper (for example, “contributions from additional cells and processes downstream of the defined optically triggered population are expected and indeed represent an important aspect of this approach”1). Moreover, the complexity of the brain dictates that such possible contributory mechanisms are more numerous than listed in the Comment2, including many other circuit and feedback mechanisms and classes of cells within neural circuitry6,7,8,9,10. As was discussed1, this is one of the most important and useful aspects of the ofMRI approach.
 https://www.nature.com/articles/nature09532

Remy Durand

Papers

Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures.

Global and local fMRI signals driven by neurons defined optogenetically by type and wiring

Optogenetic interrogation of neural circuits: technology for probing mammalian brain

Lee et al. reply