Prior Funding

Modulation of striatal dopamine (DA) signaling by various heteroreceptors is
implicated in a broad range of behaviors and disorders, including schizopherina
and drug addiction. GABA transmission is one of the important processes that
modulate DA neuronal activity. While the modulation effects can arise either
from changing firing pattern at the level of the DA cell bodies in the midbrain, or
from altering DA release at the terminal level in the striatum, it has not been
elucidated how the change of firing pattern is translated at the terminal level
under the influence of the GABAa receptors. We have previously demonstrated
that nicotine modulates DA release in a firing pattern dependent manner, a
novel finding that is critically important for understanding the information
processing in the striatum. In this proposal, we will extend the study to GABAa
receptors, and will investigate whether the filtering property is a general
phenomenon. These experiments may not only reveal an underlying general
feature of DA neurotransmission plasciticity and thus provide important insight
into the role of DA in reinforcement-related processing including drug addiction,
but will aslo shed light on the therapeutic strategies targeting the GABAergic
signaling pathway.