[FoRK] Success by degree
baisley at alumni.rice.edu
Wed Dec 4 14:19:06 PST 2013
By PhD, in particular. I'm excessively proud to report that my daughter defended in
Madison today. Glory details, below.
Please join the Neuroscience Training Program for Sarah Baisley's public thesis
defense seminar on Wednesday, December 4, 2013 at 11:00 AM in the Biotechnology
Auditorium, Room 1111, Genetics and Biotechnology Center (425 Henry Mall). Details
for her defense as well as her thesis abstract are below.
NTP Ph.D. Candidate: Sarah Baisley
Research conducted in the lab of Vaishali Bakshi, Ph.D.
Title: "Modulation of Prepulse Inhibition and Ingestive Behavior by Nucleus
Accumbens AMY-1 Amylin Receptors"
Wednesday, December 4
Biotechnology Auditorium, Room 1111, Genetics and Biotechnology Center (425 Henry Mall)
Amylin is a feeding-modulatory pancreatic peptide that crosses the blood-brain
barrier to access receptors localized within specific sites across the neural axis.
Among the densest concentrations of amylin receptors (AMY-Rs) is found in the
nucleus accumbens shell (AcbSh). The AcbSh represents an interface between the
limbic cortex and di/mesencephalic behavior effector systems, and plays a role in
both complex motivated behaviors, and more basic information-processing functions
(namely, pre-attentional sensorimotor gating). Hence, we investigated the role of
AcbSh AMY-Rs in both functional realms.
In the first set of experiments, we measured sensorimotor gating using the prepulse
inhibition (PPI) paradigm, in which sub-threshold auditory stimuli (“prepulses”)
negatively modulate the behavioral responses to subsequent superthreshold stimuli.
AcbSh amylin infusions partially reversed PPI deficits created by the
psychotomimetic drug amphetamine. These effects were limited to the AcbSh, where we
also found high levels of mRNA for RAMP-1 and CT-R, the two genetic components of
the high-affinity AMY-1 amylin receptor. In addition, blockade of AcbSh AMY-R
receptors created PPI deficits that were reversed by the antipsychotic haloperidol.
This suggests that there is an endogenous amylinergic ‘tone’ in the AcbSh that
regulates PPI via interactions with dopamine receptors. Because AMY-R are almost
absent outside of the medial AcbSh, drugs affecting AMY-1 receptors could provide a
means of selectively targeting the ventral striatum and thereby avoid dorsal
striatum-mediated side effects. Amylin is also a satiety factor, so its use as an
adjunct antipsychotic could counteract the diabetes, obesity, and other metabolic
side effects commonly seen with existing antipsychotic treatments.
In the second set of experiments, we explored AcbSh amylin’s role in appetitively
motivated behavior, by examining interactions between AcbSh-localized AMY-Rs and
mu-opioid receptors (µ-OR). Amylin infusions in the AcbSh, but not the anterodorsal
striatum, potently decreased µ-OR stimulation-induced hyperphagia at doses far lower
than needed to reduce non-opioid-driven feeding. Conversely, blockade of AcbSh
AMY-Rs significantly reversed the ability of pre-feeding to suppress µ-OR
stimulation-induced hyperphagia. This effect of AMY-R blockade was present only
after eating, when circulating amylin levels are highest. This represents the first
demonstration that endogenous AMY-R signaling negatively modulates µ-OR-mediated
appetitive responses at the level of the AcbSh.
Taken together, the results from this thesis suggest that AcbSh AMY-1 stimulation
may have antipsychotic potential, and that an endogenous telencephalic amylinergic
‘tone’ regulates sensorimotor gating and appetitive behavior.
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