Exploring adult hippocampal neurogenesis using optogenetics

In the 1980s, it was widely accepted that new neurons are continuously generated in the dentate gyrus of the mammalian hippocampus. Since its acceptance, researchers have employed various techniques and behavioral paradigms to study the proliferation, differentiation, and functional role of adult-born neurons. This literature thesis aims to discuss how optogenetics is able to overcome the limitations of past techniques and provide the field with new insights into the functional role of neurogenesis. We will review the current knowledge on both adult hippocampal neurogenesis and optogenetics, present representative studies using optogenetics to investigate neurogenesis and discuss potential limitations and concerns involved in using optogenetics

Optogenetics in primates: monkey see monkey look

Optogenetics has emerged as a powerful tool for studying the neural basis of simple behaviors in rodents and small animals. In the primate model, however, optogenetics has had limited utility because optical methods have not been able to drive behavior. Here, we report that monkeys reliably shift their gaze toward the receptive field of optically driven channelrhodopsin-2-expressing V1 neurons. This result establishes optogenetics as a viable means for the causal analysis of behavior in the primate model

Optogenetics and deep brain stimulation neurotechnologies

Brain neural network is composed of densely packed, intricately wired neurons whose activity patterns ultimately give rise to every behavior, thought, or emotion that we experience. Over the past decade, a novel neurotechnique, optogenetics that combines light and genetic methods to control or monitor neural activity patterns, has proven to be revolutionary in understanding the functional role of specific neural circuits. We here briefly describe recent advance in optogenetics and compare optogenetics with deep brain stimulation technology that holds the promise for treating many neurological and psychiatric disorders

Interrogating cellular perception and decision making with optogenetic tools.

Optogenetics promises to deepen our understanding of how cells perceive and respond to complex and dynamic signals and how this perception regulates normal and abnormal function. In this study, we present our vision for how these nascent tools may transform our view of fundamental cell biological processes

Optical excitation and detection of neuronal activity

Optogenetics has emerged as an exciting tool for manipulating neural activity, which in turn, can modulate behavior in live organisms. However, detecting the response to the optical stimulation requires electrophysiology with physical contact or fluorescent imaging at target locations, which is often limited by photobleaching and phototoxicity. In this paper, we show that phase imaging can report the intracellular transport induced by optogenetic stimulation. We developed a multimodal instrument that can both stimulate cells with high spatial resolution and detect optical pathlength changes with nanometer scale sensitivity. We found that optical pathlength fluctuations following stimulation are consistent with active organelle transport. Furthermore, the results indicate a broadening in the transport velocity distribution, which is significantly higher in stimulated cells compared to optogenetically inactive cells. It is likely that this label-free, contactless measurement of optogenetic response will provide an enabling approach to neuroscience.Comment: 20 pages, 5 figure

Separate roles of PKA and EPAC in renal function unraveled by the optogenetic control of cAMP levels in vivo

Cyclic AMP (cAMP) is a ubiquitous second messenger that regulates a variety of essential processes in diverse cell types, functioning via cAMP-dependent effectors such as protein kinase A (PKA) and/or exchange proteins directly activated by cAMP (EPAC). In an intact tissue it is difficult to separate the contribution of each cAMP effector in a particular cell type using genetic or pharmacological approaches alone. We, therefore, utilized optogenetics to overcome the difficulties associated with examining a multicellular tissue. The transgenic photoactive adenylyl cyclase bPAC can be activated to rapidly and reversibly generate cAMP pulses in a cell-type-specific manner. This optogenetic approach to cAMP manipulation was validated in vivo using GAL4-driven UAS–bPAC in a simple epithelium, the Drosophila renal (Malpighian) tubules. As bPAC was expressed under the control of cell-type-specific promoters, each cAMP signal could be directed to either the stellate or principal cells, the two major cell types of the Drosophila renal tubule. By combining the bPAC transgene with genetic and pharmacological manipulation of either PKA or EPAC it was possible to investigate the functional impact of PKA and EPAC independently of each other. The results of this investigation suggest that both PKA and EPAC are involved in cAMP sensing, but are engaged in very different downstream physiological functions in each cell type: PKA is necessary for basal secretion in principal cells only, and for stimulated fluid secretion in stellate cells only. By contrast, EPAC is important in stimulated fluid secretion in both cell types. We propose that such optogenetic control of cellular cAMP levels can be applied to other systems, for example the heart or the central nervous system, to investigate the physiological impact of cAMP-dependent signaling pathways with unprecedented precision

Timing Control of Single Neuron Spikes with Optogenetic Stimulation

This paper predicts the ability to externally control the firing times of a cortical neuron whose behavior follows the Izhikevich neuron model. The Izhikevich neuron model provides an efficient and biologically plausible method to track a cortical neuron's membrane potential and its firing times. The external control is a simple optogenetic model represented by a constant current source that can be turned on or off. This paper considers a firing frequency that is sufficiently low for the membrane potential to return to its resting potential after it fires. The time required for the neuron to charge and for the neuron to recover to the resting potential are fitted to functions of the Izhikevich neuron model parameters. Results show that linear functions of the model parameters can be used to predict the charging times with some accuracy and are sufficient to estimate the highest firing frequency achievable without interspike interference.Comment: 6 pages, 8 figures, 3 tables. To be presented at the 2018 IEEE International Conference on Communications (IEEE ICC 2018) in May 201

Tools for Controlling Activity of Neural Circuits Can Boost Gastrointestinal Research

We thank Prof U. G. Knaus and T. C. Collin for critical reading of the manuscript. GA is supported by the European Crohn's and Colitis Organization (ECCO) (J/15/2) and by the National Childrens' Research Centre (K/12/1). GD is supported by the University of Aberdeen Wellcome Trust Institutional Support Fund (105625/Z/14Z).Peer reviewedPublisher PD