15:09 jenlw: Siobhan, can you tell me a little about your background?
15:12 Siobhan: I have been studying the brain for several years now. My first introduction was during my undergraduate training at the University of Rochester
15:12 Siobhan: I continued as a technician at Dartmouth College for 3 years
15:12 Siobhan: and now I am here as a graduate student in the neurobiology and behavior program at UW
15:13 jenlw: What aspect of the brain and behavior are you particularly interested in?
15:14 Siobhan: I am particularly interested in the chemicals that the brain uses to communicate between one brain cell and another
15:15 Siobhan: Some of these chemicals have very important roles in behaviors such as drug addiction, motivation, learning and memory and many others
15:15 Siobhan: Ultimately I would like to understand how these chemicals influence behavior
15:17 jenlw: Tell me about knockout mice without dopamine! What difference do you see between these knockout mice and regular mice?
15:18 Siobhan: I am not an expert, as I am relatively new to the lab, but they are extremely sensitive to drugs of abuse such as cocaine and amphetamine
15:19 jenlw: Is anyone in your lab studying meth?
15:19 Siobhan: These mice have to be treated daily with a compound that they can convert to Dopamine
15:19 Siobhan: otherwise they die!
15:20 Siobhan: This treatment allows the mice to live day to day in the absence of their own dopamine
15:20 jenlw: Do you give them L dopa daily?
15:20 Siobhan: yes
15:21 Siobhan: There are also norepinephrine and epinephrine deficient mice in the lab
15:21 Siobhan: these mice have compromised maternal behavior as well as compromised thermoregulation
15:22 jenlw: So, the deficient dopamine mice have just enough dopamine to live for a day - and are supersensitive to dopamine. What else do you see with these mice?
15:24 jenlw: Why do they have compromised maternal behavior and thermoregulation?
15:24 Siobhan: The thermoregulatory deficiency might be due to an inability peripherally vasoconstrict
15:25 jenlw: And what do you see with nore and e deficient mice?
15:25 Siobhan: vasoconstriction is dependent on noradrenergic stimulation of the blood vessels
15:25 Siobhan: But...these mice have no norepinephrine
15:26 Siobhan: my best guess is that their olfactory system might not be intact???
15:26 jenlw: Hi, LAURA! i'm asking Siobhan about these maternally deficient mice...
15:28 Siobhan: Welcome. Laura! This is Trez - How do you like the conversation?
15:29 lstreichert: Hi-I don't seem to be able to "hear" the conversation.
15:30 jenlw: Ok, maybe you're like one of these deficient mice.....
15:30 Siobhan: Hi Laura,
15:30 jenlw: Tell me about the deficient e mice. What happens with them?
15:30 lstreichert: Definitely deficient in some way. I'd like to hear about your research, Siobhan.
15:30 Siobhan: We are discussing some of the genetically engineered mice in the Palmiter lab
15:31 lstreichert: What is the transgene?
15:32 Siobhan: Most of the mice are knockouts, not knock ins.
15:32 Siobhan: for example, the gene that codes for an enzyme has been disrupted
15:33 lstreichert: I see. Perhaps you could say a little about the difference between knockouts and transgenes, for our listener's pleasure.
15:33 Siobhan: Trangenic mice have a gene from another organism inserted into their genome
15:34 Siobhan: Knockout mice have a targeted disruption of one of their genes in their DNA
15:35 lstreichert: Does the gene that is disrupted in the mouse that you are studying have a homologous gene with a similar function in humans?
15:36 Siobhan: yes. It is an important gene that codes for the enzyme that converts dopamine to norepinephrine. Very important in humans and mice!!
15:36 jenlw: What does it do in humans?
15:37 Siobhan: The same thing. Without this gene, humans would not be able to control their sympathetic (fight or flight) nervous system efficiently
15:38 Siobhan: due to a lack of norepinephrine
15:38 lstreichert: How do you assess physiological and behavioral changes in the knockout mice?
15:39 jenlw: Does this mean you have no-violence mice?
15:39 Siobhan: good question! There are many helpful tools that we use, such as a locomotor chamber
15:39 Siobhan: learning and memory mazes
15:40 Siobhan: food and water intake
15:40 lstreichert: Do you look at sections of the brain to determine actual anatomical changes in the knockouts?
15:41 jenlw: Do they drink/eat more? Get worse at mazes? And what is a locomotor chamber?
15:41 Siobhan: yes, the mice have been thoroughly characterized (although there is always finer details to look at) and there are suprisingly few gross anatomical changes
15:42 Siobhan: Jenny - the norepinephrine deficient mice are underweight...but, they eat voraciously.
15:42 Siobhan: the catch is that they have very high basal metabolic rates and are burning through their energy stores
15:43 lstreichert: I have a few aside questions about animal care and use. Are the animals specially bred for these experiments and are the people that work with them trained to handle mice?
15:43 Siobhan: ...it is thought that they are spending a lot of energy trying to generate heat because they cannot vasoconstrict to conserve heat
15:44 Siobhan: Laura-the mice are in good hands. They are indeed specially bred. As a matter of fact, many knockouts are immunocompromised
15:44 jenlw: Do you ever pair a deficient mouse with stress to see what the outcome is?
15:45 Siobhan: and therefore need to be in specific-pathogen free environment
15:46 Siobhan: All animal care personnel and all lab members take several animal care classes
15:48 lstreichert: Siobhan, how did you get interested in being a scientist?
15:48 Siobhan: stress - great question. Norepinephrine deficient mice are extremely suceptible to seizure inducing agents
15:49 Siobhan: I had really great female role models in college. They inspired me!
15:50 lstreichert: Sorry to have aparallel conversation going. They are both pretty interesting. I also had a great female role model in college.
15:50 jenlw: Why are nor-e deficient mice susceptible to seizure agents?
15:50 Siobhan: Once I began to study the brain, my future was clear
15:51 lstreichert: Back to the mice - are the changes you see similar to any specific known drug effects?
15:51 up: Ok I have to leave for an appointment - happy chatting.
15:51 Siobhan: J- I don't know the answer to that. I will have to report back to you in a few years. It is currently being studied in the lab
15:52 jenlw: How are you studying this? (the -nor e mice and seiZURES?)
15:52 Siobhan: Laura - I can't say that the phenotype of the mice closely mimics one specific drug. However, the dopamine deficient mice are great for studying the effects of cocaine and amphetamine
15:53 lstreichert: Is there any parallel with people with Parkinson's Disease?
15:54 Siobhan: yes, in fact the mice were developed specifically to mimic Parkinson's disease (which drew me to the Palmiter lab in the first place).
15:55 Siobhan: These mice are being closely investigated for potential breakthroughs in Parkinson's Disease research
15:56 lstreichert: What a great example of the connection between animal research and advancements for humans!
15:56 jenlw: What new information is being discovered about how to treat Parkinson's Disease? - Trez
15:58 lstreichert: Another question about the knockouts - do they age normally?
15:58 Siobhan: Parkinson's patients are being treated with fetal pig stem cells. An example of this progressive research was featured on PBS last night. Check for replays!
15:59 jenlw: Do knock ins age normally?
15:59 Siobhan: As far as I know, these mice do age normally. The life span of a mouse is about 2 years.
16:00 lstreichert: Could you remind me - what is the generation time for mice. How often do they breed and how big are the litters?
16:01 Siobhan: Depending on what you knock in. There is one knock-in mouse that mimics Huntington's Chorea, I believe their life span is shorter
16:02 Siobhan: Mouse gestation is 18-19 days. Female mice come into estrus every 4-5 days, therefore they can reproduce quickly.
16:02 jenlw: You have also done some research on steroids and young women. Can you tell us about that? Trez
16:02 Siobhan: litter size ranges from 3-12 pups
16:05 Siobhan: The steroid research was very interesting. Most research on steroids of abuse focusses on males, I felt fortunate to be able to contribute to research specific to females
16:06 Siobhan: We were working with rats, adminstering different steroids. We found that female sexual behavior was significantly impaired by these steroids. Males, too
16:07 jenlw: What differences were there between female and male re:steroids?
16:08 Siobhan: Motivation can be a difficult subject to study in rats, but we attempted to do it. We wanted to see if motivation was more impaired in females compared to males
16:10 Siobhan: first, we looked at performace. Males we not physically able to copulate, females were not able to show lordosis
16:10 Siobhan: which is the position they need to be in to copulate
16:11 jenlw: Did the animals seem interested insexual behavior, but simply not able to fully engage?
16:11 lstreichert: Unfortunately, I have to leave. This has been very interesting and I will be sure to read the rest of the conversation later. Bye!
16:12 Siobhan: no, they did not seem interested. Therefore we were interested in looking at motivation. In order to do this we used a somewhat complicated behavioral apparatus in combination with
16:13 Siobhan: lesions in one of the "motivation" centers of the brain
16:14 Siobhan: Unfortunately, I had to leave and the project was somewhat backburnered. This is a common frustration as a scientist moves from one location to the next
16:17 jenlw: What are your plans for the future?
16:18 Siobhan: My goal is to have my own research program. This requires completion of this PhD program, one or two post-doctoral positions and then with luck (and determination)... a tenure track job
16:19 Siobhan: which would include teaching and research.
16:21 Siobhan: I would like to thank WABR for inviting me to the chat room. If you would like a guest speaker interested in teaching about the brain, I would love to visit a classroom or help with demonstrations!