Biomedical Engineering Reference
In-Depth Information
8.2.6
Balance Between Excitatory and Inhibitory Networks
Various oscillatory fl uctuations have been observed in the cortex, which is thought
to be associated with particular behavior. Cortical gamma oscillations (30-100 Hz)
have been well elucidated, but the neural basis of these rhythms, and their role in
animal behavior, remain unknown. ChR2-mediated photostimulation of parvalbu-
min (PV)-expressing interneurons amplifi ed gamma oscillations, whereas eNpHR-
mediated photoinhibition suppressed them (Sohal et al.
2009
; Cardin et al.
2009
).
Furthermore,
-frequency modulation of excitatory input enhanced signal transduc-
tion in cortical regions, reducing circuit noise and amplifying circuit signals. These
studies provide the fi rst causal evidence that distinct network activity states can be
induced in vivo by cell-type-specifi c activation of PV neurons, and also suggest a
potential mechanism for the altered
γ
-frequency synchronization and cognition in
schizophrenia and autism (Sohal et al.
2009
; Cardin et al.
2009
). In another recent
study, optogenetic stimulation of layer VI excitatory neurons was shown to reduce
fi ring within the upper layers of the mouse visual cortex. This suggests that activa-
tion of layer VI excitatory neurons plays an essential role in gain control within
cortical sensory networks (Olsen et al. 2012). In addition to the neurological studies
described above, optogenetic probes have been used to investigate many other
aspects of health and disease, including associative fear memory (Haubensak et al.
2010
; Ciocchi et al.
2010
), epilepsy (Tonnesen et al.
2009
), and the blood oxygen
level-dependent (BOLD) effect during functional magnetic resonance imaging (Lee
et al.
2010
).
γ
8.3
Technical Aspects
8.3.1
Molecular Aspects
Although there are notable exceptions, the most commonly used optogenetic probes
are gene-engineered versions of natural opsins, which are light-sensitive membrane
proteins through which ions are translocated in response to light stimulation at spe-
cifi c wavelengths (Kramer et al.
2009
). These probes can be utilized either to excite
the cells, to inhibit their activity, or to change intracellular signaling (Fig.
8.2
).
Probes for Stimulating Neurons
ChR2 is a nonspecifi c cation channel naturally expressed in the alga
Chlamydomonas
reinhardtii
(Nagel et al.
2003
). On absorbing blue light at an absorption peak of
480 nm, ChR2 undergoes a conformational change from the all-
trans
-retinal chro-
mophore complex to 13-
cis
-retinal (Bamann et al.
2008
). This switch causes a
