Lisa So's Abstracts

Lay Audience Abstract
Parkinson’s disease (PD) is the second most common neurodegenerative disease
with no cure at the moment. PD patients have significant loss of dopamine (DA), a
chemical necessary for normal brain function. One of the earliest indicators of PD are
vocal deficits including soft, monotonous voice and poor pronunciation, but the link
between the loss of DA in PD and vocal deficits has not been defined leading to suboptimal
treatments. Both rodent and songbird models are commonly used to study PD,
but songbirds are considered better models to study speech due to similar vocal pathways
in the brain involving DA. Song development in male zebra finches has been correlated
to human speech development, making them the best model to study the role of DA in
vocalizations. Zebra finches have two different singing behaviors - when the male bird
sings solo in his cage (undirected, UD) or to a female (directed, FD). The purpose of this
study was to determine whether the vocal behavior of the zebra finch (non-singing (NS)
vs. UD/FD) changes the protein expression of DA biomarkers in Area X, a songdedicated
region in the brain, as a first step towards understanding the role of DA in PD
associated vocal deficits. One DA biomarker tested was tyrosine hydroxylase (TH), an
enzyme that is required to produce DA. Two hours after NS or singing states (UD/FD),
the brain was extracted and Area X was tissue biopsied. The Area X tissue sample was
used to measure the changes in protein levels of TH in the different non-singing and
singing groups. The results show that TH levels were different among the different
behavioral groups. On-going experiments involve investigating the protein expression of
different DA biomarkers such as the DA receptors in Area X. Future experiments will
look at how experimentally depleting DA in Area X as in a PD state will affect the
protein levels of biomarkers for dopamine signaling in the different non-vocal and vocal
states. The goal is to understand the role of DA in normal vocal behavior as well as in
cases of dopamine depletion as in PD.

Full Abstract

Title: Behavioral regulation of dopamine biomarkers in Area X of adult male zebra finch songbirds
Authors: L. Y. So, S. J. Munger, J. E. Miller
Key words: dopamine, zebra finch, Parkinson’s Disease

Dopamine (DA) is an important neuromodulator of motor control across vertebrate
species, and under neuropathological conditions, the loss of DA in the basal ganglia leads
to Parkinson’s Disease (PD). Vocal deficits associated with PD include monotonous
voice, decreased loudness, and articulatory problems; however, the link between the loss
of DA and vocal modulation is not well-understood. In rodent and songbird models, 6-
hydroxydopamine (6-OHDA), a neurotoxin that causes dopaminergic cell death, has been
used to study the effects of DA loss on vocalizations. Zebra finch (Taeniopygia guttata)
songbirds are vocal learners and have similar dopaminergic pathways as in the human
brain making them an advantageous model to study the role of DA in vocalizations. The
zebra finch songbird model has been used to characterize the role of DA in modulating
neuronal firing patterns in Area X when the bird is singing by himself (undirected, UD)
or to a female (directed, FD). In the current study, we investigated whether the vocal
behavior of the zebra finch (non-singing vs. UD/FD) regulates the protein expression of
different biomarkers associated with dopaminergic activity in Area X, including tyrosine
hydroxylase (TH), an enzyme required for DA biosynthesis. Two hours following the
non-singing (NS) or singing states, a key time-point used to examine song-related
changes in gene expression, the brain was extracted and Area X tissue biopsied for
Western blotting. We hypothesized that TH levels in Area X would be higher during
singing versus NS as well as higher in FD than UD due to previous studies sampling DA
metabolites and given the rewarding nature of FD courtship behavior. TH levels were
differentially regulated in Area X across NS and singing states and may be regulated by
the amount of song and social-context (UD vs. FD). On-going experiments are
investigating protein expression patterns in NS and singing states for DA receptors and
other biomarkers in Area X. Future work will examine how 6-OHDA-induced DA
depletion in Area X affects DA biomarkers in different vocally-driven behavioral states.
The goal is to understand the neurobiological mechanisms whereby DA contributes to
normal vocal behavior and the consequences of DA loss as noted in PD.