Biology Reference
In-Depth Information
gene
pale
cause a dose-dependent loss of general locomotor ability (Pendleton
et al.
, 1984). The systemic administration of chemical
inhibitors of TH synthesis, such as 3-iodo-tyrosine, resulted in developmental
delay, decreased fertility and inhibition of a simple learning paradigm
(Neckameyer, 1996, 1998a,b). However, it is unclear from these studies whether
these phenotypes result from loss of DA signaling in the nervous system or from a
nonneuronal requirement for dopamine. The Drosophila
, 2002; Tempel
et al.
gene encodes two
alternatively spliced isoforms of TH: one isoform is neuronally expressed, while
the other is expressed in the developing mesoderm and required for cuticle
hardening and pigmentation (Birman
pale
et al.
, 1994; Neckameyer and White,
1993).
Several recent studies have utilized the GAL4/UAS system to address
the behavioral effects of perturbing DA neuron signaling in the Drosophila
nervous system. In one report, investigators expressed tetanus toxin in TH-
expressing neurons to block DA neuron signaling. Drosophila with most of
their DA neurons silenced are viable, display normal locomotion, and have a
wild-type (WT) appearance; however, these flies exhibit a hyperexcitable startle
response (Friggi-Grelin
, 2003). Another study made use of a transgene
encoding an ATP-gated calcium channel in conjunction with a photolabile
caged ATP. This technique allows exquisite control over depolarization, and
thereby activation, of neuron signaling in an intact animal, an emerging field
called optogenetics. Unexpectedly, photostimulation of DA neurons produced
quite differing effects dependent on the locomotor state of the flies preceding
photostimulation. One population of flies with low locomotor activity prior to
photostimulation exhibited an increased frequency of locomotion and an alter-
ation in the routes traversed following photostimulation. Photostimulation of a
second population of flies with high locomotor activity prior to photostimulation
was found to result in a transient locomotor arrest (Lima and Miesenbock, 2005).
Together, these results demonstrate that a function of DA signaling in the
Drosophila nervous system is to regulate locomotor behavior in a complex
manner.
et al.
III. DOMINANT TRAITS
A.
a
-Synuclein models
The first gene linked to a heritable form of PD,
-synuclein, was also the first of
the PD-related genes to be studied in Drosophila.
-Synuclein is a small (140
amino acids) but abundant neuronal protein that is particularly enriched in pre-
synaptic terminals. Although the precise physiological function of
-synuclein
remains to be elucidated, several studies have suggested a regulatory role for the
