Transcript Beyond BP. New ways to detect release of dopamine with PET.

Imaging Drugs in the Brain
ENAS 880 / NSCI 523
Fall 2010
Morris/Cosgrove
[email protected]
kelly [email protected]
http://tauruspet.med.yale.edu/staff/edm42/courses/ENAS_880/index.html
Quiz 1
Course business
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info posted on Evan’s website
a few classes in N203 at end of semester
lectur-ettes, followed by…
paper discussions – participation expected
paper synopses to be written, emailed
collaborative presentation or other work
what are your interests?
what are your goals?
Terms in first papers
dopamine
neuroleptic
tomographic method
spatial resolution
cyclotron (‘in-hospital’… why)
specific activity
specific binding
attentuation correction
septa
reference region
recovery coefficient
ligand vs tracer vs isotope
contrast
noise
model
compartments
steady state
structural vs functional
caudate, cerebellum
Warmup: What is this?
http://www.cscs.umich.edu/~crshalizi/
OK, start with this…
now this
functional image overlaid
on a structural image:
the ‘pixels’ in a structural image
convey some physical,
anatomical, or geographical
information about the object.
http://www.cscs.umich.edu/~crshalizi/election/
now this
functional image:
the color and size of the ‘pixels’
convey some functional
information about how the object
WORKS.
http://www.cscs.umich.edu/~crshalizi/election/
Electoral Map (Cartogram)
Every county is displayed in color according to vote (in
2004) of the majority of the voters. The size of the county
represents the number of voters. (Note that the western
plain states are smaller than the east coast.)
In this case, the cartogram shows us that –contrary to
popular belief- the country’s distribution of Dems and
Repubs was reasonably heterogeneous.
http://www.cscs.umich.edu/~crshalizi/
Our goal: Understand how
functional maps of the human brain
are used to study drugs and drug
action
what’s going on here?
Christian et al.
which ones are…functional vs structural
which ones do “detection” vs “characterization”
Fowler et al., Science & Practice Perspectives, April 2007, 4-16
what’s the modality?
what is the orientation of
the brain?
what is the orientation of
the person?
what’s the yellow stuff?
is this a single subject?
Fowler et al., Science & Practice Perspectives, April 2007, 4-16
what’s the prominent neurotransmitter in the nucleus accumbens?
Fowler et al., Science & Practice Perspectives, April 2007, 4-16
Many drugs cause release of dopamine
“… cocaine, morphine, nicotine, and ethanol share the property of increasing DA
transmission in the BNST. This effect may be related to an action at the level of
neuronal circuits activated by natural reinforcers … suggest[ing] that DA
transmission of the BNST plays a role in the mechanism of drug abuse and
addiction.”
Carboni et al, J Neurosci 20:RC102(1-5), 2000
is everyone
familiar with
this diagram?
to what other
site(s) could
we direct a
tracer?
Fowler et al., Science & Practice Perspectives, April 2007, 4-16
which one is
specific for
neurotransmitter
system?
which one is a
non-specific
marker of
‘activation’?
what are they
‘tracing’
are these
molecules
biologically the
same as their
tracees?
Fowler et al., Science & Practice Perspectives, April 2007, 4-16
which end is up?
which end has high
uptake in healthy
controls?
how do you know?
what does that
mean?
why are these
images so blurry?
Fowler et al., Science & Practice Perspectives, April 2007, 4-16
what is the claim here?
what assumption(s) is(are)
at work?
are they measuring the
phenomenon or something
related to it?
Fowler et al., Science & Practice Perspectives, April 2007, 4-16
why is most of the
brain blue?
are these images
from the start or the
end of the
experiment?
is this structural or
functional?
is this a ‘detection’
or a
‘characterization’
experiment?
Fowler et al., Science & Practice Perspectives, April 2007, 4-16
Schematic Diagram of Ligand Binding
“Rest” condition
BP = B/F
at steady state
endogenous NT
unlabeled tracer
radiolabeled tracer
Schematic Diagram of Ligand Binding
“Rest” condition
loss of receptors
BP ↓
endogenous NT
unlabeled tracer
radiolabeled tracer
Schematic Diagram of Ligand Binding
DA-release condition
DA ↑
BP ↓
endogenous NT
unlabeled tracer
radiolabeled tracer
DBP is the (fractional) difference in BP
between conditions
DBP= (BP1-BP2)/BP1