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These inverted constructs were applied, inter alia, to modulate
neural activity within the neuroendocrine system, to dissect the
impact of peptide release in specifi c target areas and to unveil the
causal relationship between activity in a defi ned neuron group and
observable behavior.
Several studies addressed the question of feeding regulation by
ARC (
arcuate nucleus
)-located neurons. POMC (
proopiomelano-
cortin
)- and AGRP-neurons, which occur intermingled and respec-
tively inhibit or stimulate feeding, were made accessible, using
POMC-Cre [
49
] and AGRP-Cre [
50
,
51
] driver lines [
16
]. Opsin
stimulation in the study of Atasoy et al. [
16
] then revealed unam-
biguously the connection between ARC-descending AGRP neu-
rons and PVN-located OT neurons. Owing to this newly discovered
contact, further attempts elucidated that AGRP/GABA release
from AGRP neurons actively suppresses OT neurons that in turn
project to the hindbrain and spinal cord areas where they mediate
an anorexic effect [
16
,
46
]. Remarkably, the stimulation of only a
small, defi ned group of cells—namely AGRP-neurons—generated
acute and goal-directed behavior without previous training or con-
ditioning [
51
]. Optogenetics could thus reveal the dedicated role
of AGRP neurons in controlling feeding behavior and mimicked,
via external stimulation, the functional implication of these neu-
rons, e.g., during states of energy defi cit.
Numerous Cre-driver lines, in majority in mice, but also in rats
[
52
], were applied in different kinds of optogenetic studies [
3
,
17
,
28
,
45
,
52
-
56
], for review see [
1
]. An overview of Cre-driver lines
is given by Madisen and colleagues [
57
], Taniguchi and colleagues
[
58
] and can also be found in the databases of the Allen Institute
for Brain Science (
http://connectivity.brain-map.org/transgenic/
search/basic
), at the Cre Driver website (
http://credrivermice.
some neuropeptide-Cre lines shall be mentioned, including gonad-
otropin-releasing hormone-Cre [
59
], corticotropin-releasing hor-
mone-Cre (JAX mice stock number 012704, MMRRC-database,
Stock Number: 030850-UCD, and also [
58
,
60
]), vasopressin-Cre
(MMRRC-database, Stock Number: 036073-UCD and 034637-
UCD), neuropeptideY-Cre (MMRRC-database, Stock Number:
036081-UCD and 034810-UCD), oxytocin-Cre [
61
], oxytocin
receptor-Cre (MMRRC-database, Stock Number: 036545-UCD,
JAX mice stock number: 008471), promelanin-concentrating hor-
mone-Cre (MMRRC-database, Stock Number: 034699-UCD),
and proopiomelanocortin-Cre (JAX mice stock number: 010714).
The precise application of virus to Cre-driver line (here Cre-
responder viruses) or wild-type animals (here i.e., specifi c promoter
viruses) is preferable over the transgene approach with direct opsin
expression. The latter are generated via BAC- or knock-in
technology, as discussed above, or via crossbreeding of Cre-driver
lines with Cre-dependent opsin lines (Rosa26 locus
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