Biomedical Engineering Reference
In-Depth Information
channelrhodopsin-2 (ChR2) in particular neurons to stimulate them specifi cally by
light. ChR2 thus allows us to control neurons with high spatiotemporal resolution.
As with calcium imaging, optogenetics provides a molecular tool with which single
neurons, or populations of neurons, within a network of interest can be studied.
8.1.1
Optogenetics
Trillions of synapses connecting neurons are included in the whole network of
the mammalian brain (Luo et al.
2008
). The components of this huge network,
such as neurons and glias, are well characterized in all areas of the brain. These
components build up not only a relatively simple system but also an incredibly
complex system, corresponding to sensory or motor processing and higher cog-
nitive functions, such as the circuits that mediate vision, motor movements,
breathing/respiration, and sleep/wake architecture. At both levels of complexity,
the relative contributions of individual cells and the synaptic connections
between them should be elucidated to understand the mechanisms of informa-
tion processing in the brain. However, precise manipulation of the activities of
the network has been extremely challenging for traditional electrophysiological,
pharmacological, and genetic methods (Luo et al.
2008
; Carter and Shieh
2010
).
While numerous successes have been reported with these classical methods, we
have faced considerable obstacles to achieving spatiotemporal precision in the
study of neural circuits in vivo. Conventional electrical and physical techniques
are spatially imprecise, since surrounding cells are also stimulated or inhibited.
Pharmacological and genetic methods yield better data than electrical and phys-
ical approaches in terms of spatial selectivity, but temporal resolution is still
insuffi cient for single action potentials. To overcome these limitations, optoge-
netics has been developed as a new set of tools to precisely stimulate (Boyden
et al.
2005
; Zhang et al.
2008
; Berndt et al.
2009
; Lin et al.
2009
; Gunaydin
et al.
2010
; Li et al.
2005
; Nagel et al.
2003
), inhibit neural activity (Chow et al.
2010
; Gradinaru et al.
2010
; Zhao et al.
2008
; Gradinaru et al.
2008
; Zhang
et al.
2007a
,
b
), or alter biochemical activity in specifi c cells (Airan et al.
2009
;
Oh et al.
2010
) with high temporal precision and rapid reversibility. These tools
are activated by light (“opto-”) and are genetically encoded (“-genetics”) to give
us specifi c control over particular populations of cells in vitro and in vivo
(Fig.
8.1
) (Zhang et al.
2006
; Gradinaru et al.
2007
; Zhang et al.
2007a
,
b
;
Zhang et al.
2010
; Cardin et al.
2010
). The precise manipulation that these new
tools permit has facilitated further progress in elucidating structural and func-
tional aspects of neural circuits.
