Jeff Edwards, MEG Final Report- 2014 Award

I) Evaluation of academic objectives of the proposal

The objectives of this award were met, especially in regard to the mentoring focus of the award. The students have been mentored and trained in an effective manner as outlined in my Mentoring Plan (abbreviated below). This includes mentoring students in research, writing, publishing, presenting at conferences, etc. Indeed, one measure of the success of mentoring is demonstrated by the fact that all the students graduating from my lab during this time were accepted to the professional school of their choice (see students listed below). Research, especially where the students are actually involved in all aspects of it including data collection and analysis, as well as publishing can play a major role in their acceptance to professional schools and set them apart from other candidates.

Regarding the research towards funded by this award we have had several international and regional conferences and published abstracts, with the centerpiece publication of the project anticipated to be submitted next year, as well as other manuscripts related to the project peripherally either in preparation, submitted or published. There were many student co-authors on these manuscripts and abstracts.

Student research presentations given include at the international Society for Neuroscience meeting in Chicago and at the Faculty for Undergraduate Neuroscience meeting; as well as the regional Intermountain Society for Neuroscience Symposium and state Utah Conference on Undergraduate Research. Data was also used to submit a NIH R03 grant proposal in 2015.

Overall, we have made excellent progress with the time and money that we have had to work with on this project, and in student mentoring. I am happy with the progress, which in no way could have happened without this MEG award to provide the needed supplies and student support over the last two years. We have really provided a successful and meaningful mentoring experience for the students involved, and at the same time produced a lot of meaningful and compelling data related to exercise and stress.

II) Evaluation of the Mentoring environment

The following is my philosophy of mentoring: 1) Teach the fundamental elements of hypothesis driven research. 2) Allow students to explore their own interests within the realm of the laboratory umbrella. 3) Provide students with the time, personal supervision and overall training they need to be successful individuals in the lab and in their futures, professionally and academically. 4) Use laboratory meetings, journal clubs, attendance at professional meetings, presenting posters as an essential way to train students to develop critical analyzing and thinking skills as well as oral presentation skills. 5) Encourage student development through grant writing, training experiences by allowing students to teach each other and collaborate through group work. 6) Encourage positive interactions with myself and others in the lab. 7) Prepare students with the professional skills required beyond the undergraduate degree in their schooling and professions by accomplishing the aforementioned aims.

To help accomplish this general goal of mentoring as listed above I have several evaluation endpoints for the students to accomplish and tools to do it. 1) Initially, I use an undergraduate training program as a tool to teach students. All undergraduates go through a training program before they can enter the lab to perform experiments. The training is a collaborative effort between my lab and several others with the overall goal of providing consistent, general laboratory training to all new students. This training includes safety, animal handling, and a variety of laboratory skills. All of this is done under the supervision of advanced undergraduate and graduate students as well as myself. 2) New students entering the lab also receive 3-5 hours of background training together with me the first month they are in the lab. This background training is designed to update their basic understanding of learning and memory as well as reward/addiction science and to get them excited about the research by explaining what the experiments are and what they will be doing in the lab and why. 3) All students are expected to acquire good, publishable data. This is ensured by weekly lab meetings where the students present their data and we review it together. I also watch students in the lab doing the experiments at least weekly to ensure the experiments are performed properly, that they are learning from the experience, and that they have a better mentored experience than undergraduates who are left to work on their own with little or no guidance. 4) They must learn to present, not just their data, but scientific information to others. Initially this is practiced at laboratory meetings with their own data, then students present at journal clubs and finally at conferences. Through this process they learn good oral communication skills, how to present data to others as well as get to know and discuss science with researchers from around the world. I had 4 graduate students and 11 undergraduates travel to different meetings to present their data in the last two years (department funds also helped with the travel costs for this many students). 5) I have my students apply for internal competitive research grants and my graduate students for NIH pre-doctoral grants. Four undergraduates were awarded ORCA grants in 2014 and two in 2015. This has given them the opportunity to research different project ideas, search scientific databases and write their own grants with minor editing help from me. I attempt to make this process as independent as possible, yet guided, providing an overview for how to write a successful grant application. 6) I want the students to publish. While I discussed this above I think it worth mentioning that I have many undergraduates who will be co-authors on manuscripts.

The research experience students received in my lab was a key for most getting acceptance into professional school. All my students who have finished have been accepted into the graduate or professional school of their choice (see section III below). In conclusion, the students in my lab are getting excellent mentoring and training as illustrated by the tangible products of research listed in section IV below. This experience is going to be useful in their future and in getting excepted and succeeding in the professional school of their choice, which I think is one of the main overall purposes of the MEG award while establishing lasting and meaningful relationships with myself and others in the lab.

III) List of students who participated

Profile of Undergraduate Students Previously Trained (2014–2015)
Collectively, 100% of the students completing training in my lab in the last 2 years were accepted to the professional school of their choice or are currently Appling.

Grad.	Student Name	Current Status (School)	Grad.	Student Name	Current Status (School)
Apr 14	Zach Hopkins	Med school, Univ. of Utah	Apr 14	NathanChristensen	Applying, med school
Apr 14	Brittany Harrison	Applying, grad school	Apr 14	Bradley Prince	Med school, Univ. of Calgary
Apr 14	Bethany Walker	Med, Accepted	Aug 14	Sarah Davis	Applying, pharmacy school
Apr 14	Dane Lyman	Med, UCF	Apr 15	Deson Haynie	MPH; John’s Hopkins
April 15	Sam Lo	Med school, applying

Current undergraduates (11)

Many of my current students were involved as well. All these students plan to go on to pursue graduate, medical, dental, PA, physical therapy or MD/PhD degrees: Jake Peterson, Oliver Moore, James Call, Jacob Welch, Tyler Hammond, Jorden Barrow, Cole Romney, Bethany Borup, Lindsey Aponik, Paul Baker, Zoie Badura.

All students were involved in one of 3 groups, with some doing electrophysiology, others doing molecular biology and immunocytochemistry, and some doing behavior. These students represent those who were mentored in my lab and acquired the data used for the grant applications, abstracts, publications and presentations listed above. Again, they also collectively were awarded 5 ORCA grants. The students also won two travel awards for their presentations at conferences in the last two years and three graduate fellowship awards. I have had some fantastic undergraduates who have done a great job with these projects.

IV) Description of results/findings

Again, regarding articles using money from the MEG we have published one paper, have another submitted and two nearing completion. We published three abstracts, presented our data at regional and international meetings, and used this data for a NIH R03 grant. Finally, the major manuscript supported by the award we anticipate will be submitted next year after new molecular biology data is added.

One of our goals was to investigate the role of exercise in mitigating the negative impact of stress. While it is known that exercise enhances synaptic plasticity and stress depressed this plasticity in the hippocampus, the memory center of the brain, the effect of exercise on stress-induced impairment in memory was never done in the same animal. Our data illustrate that exercise can indeed reverse some of the negative consequences of stress on memory. After we demonstrated this at the physiological level in brain slices we did behavioral experiments using radial arm maze to determine these effects on the whole animal level. Finally, we introduced more data that we did not propose for the initial MEG, but we considered critical for the success of the project, and that was to examine the molecular pathway induced by exercise that alleviated the negative impacts of stress on memory. Therefore, we employed PCR probing various pathways involved in stress and exercise.

Data in these publications was acquired using the MEG awards:

Publications:

1. Merrill CB, FriendLN, Newton ST, Hopkins ZH, Edwards JG. Ventral tegmental area dopamine and GABA neurons: Physiological properties and expression of mRNA for endocannabinoid biosynthetic enzymes and type I metabotropic glutamate receptors. Scientific Reports. In Press.
2. Taylor D, Burman PN, Wilcox R, Merrill CB, Ringer K, Poole B, Sudweeks, SN, Edwards JG, Arias HR, Steffensen SC. Acute/chronic nicotine effects on GABA in the VTA. Submitted.
3. Cordner R, Mayo J, Ventura J, Badgley C, Wallmann A, Andreasen B, Edwards J, Capecchi M, Bridgewater L. Mice Bearing a Targeted Mutation of nBmp2 Display Decreased Memory Capabilities. To submit early 2016.
4. Friend L, Williamson RC, Merrill CB, Newton S, Christensen M, Edwards JG. Hippocampal stratum oriens interneurons express endocannabinoid biosynthetic enzymes and undergo anandamide-dependent potentiation. In Progress. To submit Feb. 2016

Data:

Figure 1. Field Electrophysiology of CA1 LTP. Field electrophysiology data illustrate that while exercise enhances LTP and stress reduces it, when both are combined in the same animal, exercise mitigates the negative impact of stress, and LTP is returned to control levels, but not to exercise only levels. Exercise + stress is significantly (p < 0.05; ANOVA or t test; n= 9-12 for each group) greater than stress alone. Exercise mice averaged 5.3 ± 0.32 km/day running and the two exercise groups were not significantly different from each other. Insets: example traces taken during baseline (black) and 25-30 minutes (red) post-theta burst, used to induce LTP (top to bottom: Sedentary control, Stress, Exercise + Stress, Exercise).

Figure 2. Radial Arm maze. A) Data illustrate both stress groups tend towards making more working memory errors than both exercise groups. B) During the first week of training exercise, mice tend to perform slightly better as noted in distance traveled to complete the radial arm maze. This effect is not noticeable in the last few weeks of performing the maze.

Figure 3. Quantitative PCR of BDNF from four mouse groups.
Exercised animals (blue) have increased BDNF levels compared to other groups (n=4-8 for each group) as is expected. These studies are only part way through completion, however they have been included to demonstrate our ability to perform qRT-PCR on mice for important elements in the exercise/stress pathways and that the data is trending the direction we would expect for our hypothesis. Relative levels of expression are normalized to sedentary no stress controls (pink).

V) Description of how the budget was spent

The following is a list of approximately how much in each major category was spent using the MEG funds awarded.

1) Supplies: chemicals, salts, drugs, glassware, oxygen, etc.	$3,500
2) Physiological equipment (electrodes, pipette glass, etc.)	$2,000
3) PCR supplies (RT-mix, tubes, primers, probes)	$3,500
4) Animals (rats)	$5,000
5) Student Salaries	$4,000
6) Student Travel	$2,000