Title: Development of DA and 5HT neurons involved in rewardassociated behavior in zebrafish
1Development of DA and 5HT neurons involved in
reward-associated behavior in zebrafish
Su Guo, Ph.D.
University of california, San Francisco
23-day old zebrafish labeled with anti-TH and 5HT
antibodies
3Questions
- Do zebrafish have reward-associated behavior?
- Experience-dependent morphine preference
- Do the basal forebrain DA/5HT neurons play a role
in this behavior? - The too few mutant
- How is the development of basal forebrain DA/5HT
neurons regulated? - The foggy mutant
4Zebrafish a vertebrate genetic model organism
Small-size
High fecundity
Rapid development
In vivo tracing of biological processes
Easy to maintain In large numbers
Optically transparent
5What is reward-associated behavior?
- A prior exposure to a substance elicits a
preference behavior for the substance - Spend more time in the substance-paired side
(CPP) - Self-administer the substance
6Studying reward-associated behavior in larval
zebrafish
- Larval zebrafish are amenable to genetic analysis
and the study of cellular mechanisms - Larval zebrafish are free-living (food hunting,
escaping) - The nervous system of larval zebrafish is more
plastic than adult zebrafish.
7Choice chamber
8Larval zebrafish show experience-dependent
preference for morphine
9Morphine preference is dependent on opioid
receptors
10The too few mutant
11The basal forebrain DA/5HT neurons are required
for morphine preference behavior
12Functional analogy of zf basal FB to mammalian MB
DA neurons
13How is the development of basal FB DA and 5HT
neurons regulated?
- Will the mechanisms be homologous to mammalian FB
or MB neurons? - What are the genes and pathways involved in the
development of these neurons?
14Mutagenesis screen
15Mutations affecting the development of basal FB
DA/5HT neurons
- too few
- motionless
- twin-of-motionless
- foggy
16The foggy mutant
WT
foggy
17foggy encodes a regulator of transcription
elongation
18The importance of regulating transcription
elongation during development
promoter
Transcription initiation
Transcription elongation
19foggy expression
20The foggy mutation selectively disrupts its
repressor activity
21Question
- What genes are de-repressed that leads to
defects in DA/5HT neuron development? - Micro-array study
- How is foggys repressor activity regulated
during development? - Focus on the function of the C-terminal domain,
where the foggy mutation resides.
22Summary
- Zebrafish is an attractive genetic model organism
to study - the development of specific neuronal types.
- The developmental alteration that leads to
abnormal reward-associated behavior.
23Acknowledgements
Reward-associated behavior in larval zebrafish
Sandrine Bretaud
Brent Lockwood
Foggy downstream tergets
Keerthi Krishnan
Foggy regulation
Jae-yeon Jeong
Arnon Rosenthal (Rinat Neuroscience)
Mark Fishman (Novartis)
Wolfgang Driever (University of Freiburg)