Deciphering Memory Function with Optogenetics

doi:10.1016/B978-0-12-420170-5.00012-X

Progress in Molecular Biology and Translational Science

Volume 122, 2014, Pages 341-390

https://doi.org/10.1016/B978-0-12-420170-5.00012-X Get rights and content

Abstract

Optogenetics has accelerated the field of neuroscience by overcoming many of the spatial, genetic, and temporal limitations of previous techniques to control neural activity. The study of learning and memory has profoundly benefited from these tools mainly from their use in rodents. New insights have been made regarding the involvement of specific cell types or populations of synapses in the acquisition, consolidation, and retrieval of memories. The cellular specificity and temporal precision of optogenetic manipulations have also shown to be useful to study synaptic mechanisms supporting learning and memory including long-term synaptic plasticity. Recently, new light-sensitive molecules have been developed to control intracellular pathways or gene expression, which promise to enhance our understanding of the molecular mechanism of memory function.

Section snippets

Light-sensitive molecules

Optical control of neuronal activity was initiated in 1971 when Richard Fork activated aplysia abdominal ganglion neurons with the light-sensitive protein bacteriorhodopsin (BR).¹ In 1983, Faber and Grinvald successfully initiated action potentials in neurons using a fluorescent dye and light.² Later, Schmucker et al. combined a chromophore and light amplification, via stimulated emission of radiation (laser), to inhibit cells in larval Drosophila.³ In 2002, Zemelman and colleagues created an

Optogenetic Manipulation of Memory

Optogenetic strategies now allow neuroscientists to manipulate defined cell populations with high temporal precision during the different phases of memory: learning (acquisition), storage (consolidation), recall and extinction. In the acquisition phase of memory, an animal first learns to associate an unconditioned stimulus (US), an innately negative or positive stimulus, with a conditioned stimulus (CS) previously neutral. When a CS predicts a US, the animal adapts its behavior to optimize

How optogenetics unraveled pathway-specific long-term synaptic plasticity

Donald Hebb (1949) speculated that psychological concepts could be represented by simultaneous activity of many nerve cells distributed throughout the brain, which he called a cell assembly. He postulated that cell assemblies are formed by an amplification process taking place in all synapses between active nerve cells during learning. This process of synaptic strengthening depends on coincident neural activity of pre- and postsynaptic neurons and was later called Hebbian learning. Decades

Conclusions

Elucidation of the neural substrates underlying learning and memory is facilitated by tools that precisely control neural activity and compatible readout methods. Optogenetics can directly probe the causal role of circuit elements with millisecond timescale and cell-type-specific resolution and can be coupled with electrophysiology and freely moving behavior in mammals. This new way of probing the neural circuits underlying learning and memory has provided considerable insight into the function

Acknowledgments

This work was supported by the JPB Foundation, Picower Institute Innovation Funds, The Whitehall Foundation, the Picower Institute and Department of Brain and Cognitive Science startup funds (MIT), and the Klingenstein Foundation Award. Anna Beyeler is a postdoctoral fellow of the Swiss National Science Foundation (SNSF).

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Chapter Twelve - Deciphering Memory Function with Optogenetics

Abstract

Section snippets

Light-sensitive molecules

Optogenetic Manipulation of Memory

How optogenetics unraveled pathway-specific long-term synaptic plasticity

Conclusions

Acknowledgments

Neuron

Curr Biol

Biophys J

Neuron

Cell

J Biol Chem

J Biol Chem

J Biol Chem

Mol Ther

Mol Ther

Neuroscience

Mol Ther

Curr Opin Neurobiol

J Neurosci Methods

Neuron

Comp Immunol Microbiol Infect Dis

Neuron

Neuroscience

Biol Psychiatry

Neurobiol Learn Mem

Hear Res

Neuron

Neuron

Neuron

Neuron

Laser stimulation of nerve cells in Aplysia

Science

Identification of presynaptic neurons by laser photostimulation

Science

Chromophore-assisted laser inactivation of patched protein switches cell fate in the larval visual system of Drosophila

Proc Natl Acad Sci USA

Controlling neuronal activity

Am J Psychiatry

Principles for applying optogenetic tools derived from direct comparative analysis of microbial opsins

Nat Methods

Channelrhodopsin-2, a directly light-gated cation-selective membrane channel

Proc Natl Acad Sci USA

Neural substrates of awakening probed with optogenetic control of hypocretin neurons

Nature

An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology

J Neural Eng

Millisecond-timescale, genetically targeted optical control of neural activity

Nat Neurosci

Multimodal fast optical interrogation of neural circuitry

Nature

Targeting and readout strategies for fast optical neural control in vitro and in vivo

J Neurosci

High-efficiency channelrhodopsins for fast neuronal stimulation at low light levels

Proc Natl Acad Sci USA

Ultrafast optogenetic control

Nat Neurosci

Neocortical excitation/inhibition balance in information processing and social dysfunction

Nature

Red-shifted optogenetic excitation: a tool for fast neural control derived from Volvox carteri

Nat Neurosci

Structural guidance of the photocycle of channelrhodopsin-2 by an interhelical hydrogen bond

Biochemistry

Bi-stable neural state switches

Nat Neurosci

High-performance genetically targetable optical neural silencing by light-driven proton pumps

Nature

Amygdala circuitry mediating reversible and bidirectional control of anxiety

Nature

Cholinergic interneurons control local circuit activity and cocaine conditioning

Science

Temporally precise in vivo control of intracellular signalling

Nature

Light-driven activation of β2-adrenergic receptor signaling by a chimeric rhodopsin containing the β2-adrenergic receptor cytoplasmic loops †

Biochemistry

Optical control of metabotropic glutamate receptors

Nat Neurosci

The molecular biology of memory: cAMP, PKA, CRE, CREB-1, CREB-2, and CPEB