Dr. Rob Jackson, Director
Center for Neuroscience Research
Director's Message

This is the seventh year that the Center for Neuroscience Research (CNR) has been supporting shared core facilities at Tufts University School of Medicine. For those of you new to Tufts, the CNR came into existence in 2003 coincident with the award of a P30 center grant from the National Institute of Neurological Disorders and Stroke (NINDS). We renewed the grant for an additional 5 years in 2008 and also obtained a supplemental equipment award from NINDS this past year. The supplemental award will provide needed new equipment for 3 of the 4 CNR core facilities (see core descriptions below).

The mission of the CNR continues to be the provision of scientific instrumentation and technical expertise in support of neuroscience and other research activities at Tufts University and its affiliated hospitals. The center provides core facilities to support research requiring biological imaging (fluorescence, confocal and 2-photon), electrophysiology, rodent behavioral testing and genomics/computational biology. Each of the 4 shared CNR cores is supervised by Ph.D.-level managers and other personnel who provide training on instruments and technical expertise for carrying out studies and analyzing experimental results. CNR center activities are managed by a full-time administrator, Ms. Megan Morgove, who arrived at Tufts in August of last year. Ms. Morgove is located in Stearns 301; please come by to meet her and discover more about our center.

Thanks to generous support from the Tufts Medical School Dean and the Vice Provost’s office, the CNR is able to continue supporting two different small grant initiatives. Both provide resources to investigators who wish to obtain preliminary results that will support an external grant submission. The first is a collaborative pilot grant award that aims to stimulate collaborative neuroscience at Tufts. The second mechanism is a core award, which provides resources – to be used in a CNR core – sufficient for investigators to carry out a limited set of experiments to acquire needed experimental results.

In addition to supporting research cores, the CNR continues to host seminars and workshops of value to neuroscientists and other investigators at Tufts. In the past year, the center co-sponsored the annual Tufts Neuroscience Symposium & Shucart Lecture.as well as seminars and workshops in genomics.

The CNR has been successful in large part because of the dedicated efforts of participating faculty and staff. We continue to attract talented individuals to the center and these represent the most important resources for the Tufts community. Contact information for all these individuals is included in this newsletter, and can also be found on the CNR website.

Please take advantage of CNR core facilities – they are open to all Tufts investigators. For more information about our center, you may contact any of the core directors or managers. Our goal is to support your research efforts!


Rob Jackson, Director
Tufts Center for Neuroscience Research


 


Spotlight: Isabel Quadros | Behavior Core Manager

The CNR welcomed Dr. Isabel Quadros in February ‘09, as the new Behavior Core manager. Her expertise in behavioral techniques and animal handling has proven an integral contribution to this successful and busy core. It is hard to imagine now the facility without her! Already a part of the Tufts family, Isabel made the transition to the CNR from her post-doctoral appointment on the Medford campus in the Psychology Department, where she worked under the guidance of Dr. Klaus Miczek. To Tufts University she traveled a much greater distance – from Sao Paulo, Brazil, where she grew up and also earned her Ph.D. in Psychobiology at the Federal University of Sao Paulo. Isabel has both a keen interest and extensive experience in investigating the behavioral effects of drug and alcohol abuse using animal models. While eager to continue her own research, Isabel also enjoys the teaching component of her new position. “It is exciting both to witness the different research projects going on, and to help investigators create reliable studies with the multiple behavioral techniques available.”

Behavior Core Manager Dr. Isabel Quadros, and student assistants Anthony Liberti, Frances Ding, and Max Adams
Q: Having been a part of the Psychology Department for three years, you are not new to Tufts University. How do you now like your new home at the CNR?
A:The interactive environment here is very exciting for me. I get to work with numerous investigators from Tufts and from other institutions. It is wonderful to be a part of a research facility that is available to multiple users – the access to all users across our four research cores encourages collaborations and learning.

Q: What are your own research interests?
A: My focus began in the pharmacology field. After being exposed to behavioral research in an undergraduate course, which is also when I first worked with mice, I found that I wanted to incorporate a socially relevant component in my work. My interests lie in neuropsychiatric disorders and, more specifically, how changes in the brain underlie changes in behavior in the context of such disorders. My recent work has concentrated on drug and alcohol abuse, using self-administration procedures with mice to study connections between stress, aggression, and alcohol and cocaine use.

Q: Has your research allowed an exposure to and knowledge of a variety of behavioral techniques?
A: The word “behavior” quantifies such an enormous range of measurable factors, from memory and learning to motor activity, social and emotional behaviors. There are many existing models for observing and measuring each one of these types of behaviors. The effects of alcohol and drugs of abuse can be assessed using several different behavioral procedures, since these drugs can produce “pleasurable” rewarding effects, motor stimulation, sedation, motor incoordination, etc. I have also been interested in how stressful events (i.e., physical stressors such as restraint stress, or social stressors such as maternal separation stress, social defeat)
can promote increased vulnerability to drug taking and increased sensitivity to some behavioral effects of drugs. My experience mostly focused in techniques such as locomotor assessment, drug self-administration, social stress and social interactions (aggressive behaviors). In addition, managing the CNR’s Behavior Core has exposed me to even more techniques (especially multiple types of learning and memory tests), as users come in and have different research needs. I learn from the expertise of our users, and am able to offer my own expertise as well.

Q: Does the CNR’s Behavior Core facility support these techniques?
A: We are certainly moving in that direction. Already we have a large amount of equipment to support many different behavioral techniques, and we are acquiring more! For example, users can take advantage of our set-ups for spatial memory testing (radial arm maze, Morris water maze, Barnes maze), emotional memory (fear conditioning), motor coordination (rotarod test), anxiety (elevated plus maze, startle response), depressive-like behaviors (Porsolt Forced Swim Test, Tail Suspension Test), and pain (hot plate test, tailflick test). We have just received a new four-station fear-conditioning system, and we are looking forward to receiving a mouse operant self-administration set-up for drug/alcohol studies in the near future.

Fear-conditioning system in the CNR Behavior Core
Q: Any up-coming events/changes you’d like to share with us?
A: The Behavior Core is working towards increasing its capacity for even more adequate testing. With the CNR’s recent NIH supplement award, I am excited to add new equipment for fear-conditioning and self-administration testing. I am also looking forward to offering online tutorials in the form of short videos, demonstrating some simple behavioral techniques as well as how to use the software that we provide. As our usage
grows, space in the core will continue to be an obstacle. To accommodate increasing interest in using our facility, I am making changes to the set-ups of our testing rooms, allowing equipment to be moved in and out as needed.
Q: Is there any specific information you would like existing/future CNR users to be aware of?
A:When working with researchers, I like to highlight the importance of proper animal handling and it is my pleasure to show users how to best handle their animals before and after experiments. It can make all the difference in the reliability of an experimental design. Data collected from an experiment should show the behavioral effects of your manipulation (whether a genetic, pharmacological manipulation), and not be biased by the experimenter’s effects or expectations. As much as possible, automated testing equipment is used in the Core, which helps avoid some of the bias in behavioral testing.

Q: What, in your opinion, are the greatest benefits and the most exciting developments of behavioral research today?
A: I’ve noticed a shift in how behavioral research is valued in areas that typically focus in cellular and molecular investigation. It’s exciting to see more and more the incorporation of a behavioral component into such projects, thus creating more robust results, and showing more “real life” applications. This phenomenon is not limited to the behavioral field however. Research is moving to a place where no one field can stand alone, and experimenters are looking to bridge the gap between micro and macro-level projects. The CNR facilities are right in line with this trend. With multiple accessible cores and experienced staff, a researcher can integrate different methods across fields to create well-rounded studies.

 


Tufts Imaging Facility @ the CNR

Alenka Lovy-Wheeler, PhD
Imaging Core Manager
Dr. Alenka Lovy-Wheeler manages the Tufts Imaging Facility (TIF) located in Stearns 207. Confocal/2-photon microscopy and laser capture microdissection, spinning disk confocal microscopy, and image deconvolution are available through the core, making use of facilities in multiple locations. An additional part of the Imaging Core is the Zeiss Axioplan microscope located in Arnold 309, and managed by Dr. Shui-Ying Ng. This instrument is configured for fluorescence microscopy, brightfield and differential interference contrast (DIC) imaging, and has image acquisition capabilities.

Users of the imaging facility are asked to read Imaging Facility Updates on the core blog (see link below). The blog reports equipment status and any instrument problems, as well as the configuration of the microscope (upright or inverted) and the date that data will be erased from the hard drive (every two weeks). If technical assistance is required for instrument usage, please e-mail Alenka before reserving a time.

UPDATES

  •    » Keeping up with the latest imaging techniques available, the Imaging Facility strives to offer equipment demos, and to search for ways to bring these new techniques to its users. Check the Imaging Facility Blog for news on a near-future demonstration of the latest trends in high-end confocal Raman microscopy.

  •    » Do you have a colocalization study? The Tufts Imaging Facility has the opportunity to test samples with a stimulated emission depletion (STED) microscope, and explore the possibilities of bringing this technology to Tufts. Contact Alenka for more details.

  •    » A new research storage drive for your confocal data has been created! Your work can now be saved on the Imaging Core Workstation during the progression of your project.

  •    » New Equipment!!! The CNR is excited to be acquiring a Live Cell inverted microscope, which, in addition to live-cell imaging capabilities, will also include Total Internal Fluorescence Microscopy (TIRFM).
 


The CNR Genomics Core

Lakshmanan Iyer, PhD
Genomics Core Manager
FOCUS:
INGENUITY PATHWAYS ANALYSIS (IPA)


We are happy to announce the renewal of our software license for a valuable analysis tool known as Ingenuity Pathway Analysis. It consists of highly structured and computable findings expertly extracted from scientific literature. This extensively curated tool provides a unique foundation to interpret your high throughput experiments, and can also be used for hypothesis generation relating to your favorite gene or pathway.

Contact Lax Iyer for more information!
The CNR Genomics Core is directed by Dr. Alan Kopin, and managed by Dr. Lakshmanan (Lax) Iyer and Chris Parkin, MS. The mission of the core is to provide investigators with tools and services for keeping up with advances in the field of genomics, with an emphasis on neuroscience research. While gene expression experiments tend to be the most widely used service offered by the genomics core, we are always happy to help users with any of their computational needs.  Whether it be querying online resources, sequence analysis, statistical analysis, data mining, or to discuss new project ideas, we're here to assist you.  In addition to our wide range of accessible computational biology tools and databases, we have a number of software licenses including Ingenuity Pathway Analysis, Geneious, S-Plus and TRANSFAC.  If computing power in your own lab or office is a problem, we offer use of powerful PC and Mac workstations to all users. Alternatively, we can help to get you started on the Tufts Bioinformatics Linux Cluster provided by the University Information Technology services.

For quantitative and qualitative analysis of various biological samples we are equipped with a Nanodrop spectrophotometer and Agilent BioAnalyzer. Two Stratagene thermocyclers (Mx4000 and Mx3000P) are also available to users interested in quantitative PCR (QPCR). To sign up for time on either of these machines please see the QPCR Sign-Up Calendars. This equipment is located in room 208 of the Stearns Building.

Chris Parkin, MS
Bioinformaticist - Genomics Core
WHAT'S NEW

  • “Free Chat Fridays”! No appointment needed, no e-mail swapping necessary: a Genomics Core manager will be available during the afternoon of every Friday afternoon to chat with you about a project, answer any questions big or small, and share with you how Genomics/bioinformatics can enhance your research.
  • Be on the lookout for e-mail announcements regarding upcoming Bioinformatics training seminars! Throughout the year we organize hands-on training courses to highlight essential genomics resources, examples of which include the Ingenuity Pathway Analysis tool, Mouse Genomic Informatics resources, and the UCSC Genome Browser. We’re open to suggestions, so please let us know of any tools or resources that you’d like to see included in this lineup.
  • High-throughput sequencing (HTS): Also known as next-generation sequencing, HTS technologies are revolutionizing the way biologists acquire and analyze genomic data. Biological problems such as genomic assembly, polymorphism identification, novel transcript discovery, gene expression analysis and regulatory mechanisms may all be explored using this method. . We offer access to these technologies such as mRNA-Seq: Quantitative identification of expressed RNA transcripts, Chip-Seq: Identification of genomic regions that bind to a protein of interest, esp., transcription factors and, Digital Gene Expression: Quantitative resolution of the number of transcripts of all the expressed genes. We will help you to address the challenge of analyzing the humongous amount of data generated and make biological sense of it.

Periodically check the Genomics core websitefor updates as new tools are developed. For further questions, please contact Lax or Chris at Lax.Iyer@tufts.edu or Christopher.Parkin@tufts.edu, respectively.
 


The Electrophysiology and Biophysics Core Facility (EBCF)

Chuang Du
Electrophysiology Core Manager
What can we do for you?
The EBCF has finally joined the other CNR cores in the Medical Research building! The facility, now located in Arnold 106 of the M&V complex, provides equipment, expertise, and training to non-electrophysiologists interested in using these methods to broaden their own research programs. Under the able day-to-day management of Dr. Chuang Du, and the direction of Dr. Kathy Dunlap, the CNR’s EBCF has established itself as a valuable resource with its facilities and expertise for many Tufts researchers, and continues to expand its offerings. The EBCF offers three electrophysiology setups: a dissociated cell recording setup, a single cell slice recording setup, and a brain slice field potential recording setup. Each setup is either currently being updated or has recently been updated or improved. The EBCF has helped and collaborated with many projects and continues to attract new users. These works result in numerous publications and successful grant applications. With help of the EBCF, several labs have or are in the process of establishing electrophysiology of their own. Shabrine Daftary, a postdoctoral associate in Dr. Maribel Rios’ lab has been the single cell slice setup’s most active user. This setup allows Shabrine to study the role of Brain Derived Neurotrophic Factor (BDNF) in serotonin receptor signaling in the brain, with the goal of establishing a new slice recording setup in the Rios’ lab that is now accomplished.

Dissociated cell recording setup in the CNR's
Electrophysiology Core
NEW EQUIPMENT! In other exciting news, we are looking forward to soon acquiring new equipment for our electrophysiology rigs. Due to a recent supplement award, our single cell slice recording rig will be enhanced with a multi-manipulator system an accupulser signal generator. We will also introduce a second field/single cell slice recording rig, as well as a Nikon microscope with epifluorescence capability.

We've Moved!!!
On January 7th, 2009, the EBCF relocated to the first floor of the Arnold wing of the M&V complex, in room 106. The new office of core manager Dr. Chang Du is located next door in room 109b. Director Dr. Kathy Dunlap is also close by, on the second floor of the Stearns wing.


For more information about EBCFs current and future services, fee structure, etc., please visit the electrophysiology core website or call Kathy Dunlap (64942) or Chuang Du (64938).
 


PILOT AWARDS 2009

The CNR Pilot Award has been in place for five years now, and is awarded to support collaborative projects amongst Tufts neuroscientists, particularly with a view to gathering preliminary data that might eventually contribute to an NIH grant submission. As always, we would like to thank the Office of the Vice Provost and the Medical Dean's Office for their generous funding that makes this effort to foster collaborative research a possibility. The 2009 recipients are as follows:

Drs. Michelle Jacob, Philip Haydon, and Klaus Miczek were awarded Pilot funds this year to support their project, entitled "A new transgenic mouse model of cognitive impairment.” The project involves the complementary expertise of these three researchers who have generated a new transgenic mouse model of cognitive impairment during development. They will use the four CNR cores to define molecular, functional and behavioral changes caused by APC depletion in excitatory neurons of the mouse brain. These pilot studies will provide critical insights into molecular mechanisms responsible for mental retardation and autism in humans with APC loss-of-function gene mutations. Dr. Larry Feig and Dr. Leon Reijmers are collaborating on a project entitled, “In-vivo neural circuit responses to altered plasticity as a result of GRF1 or GRF2 knockout,” and using the molecular understanding of LTP and LTD to study how changing synaptic plasticity in-vivo alters the way a neural circuit stores a memory. The data will demonstrate the feasibility of an integrative approach that combines highly specific molecular manipulations with circuit and behavioral analyses. This integrative approach is crucial for a full understanding of how the brain stores memories. The new fear-conditioning system in the CNR Behavioral Facility will be used in this project, as well as epifluorescence microscopy in the Imaging Core. A third award was given this year to Drs. Stephen Moss, Aki Takahashi, Joseph DeBold, Klaus Miczek, Miho Terunuma, Raquel Revilla-Sanchez, and Philip Haydon for their collaborative work on the project, “GABAB receptor modulation of dorsal raphé nucleus on escalated aggression in mice.” Their research aims to identify neuronal pathways underlying escalated aggression induced by GABAB receptor activation in the DRN using genetic, pharmacological and biochemical techniques. All behavior analyses will be performed in the CNR’s Animal Behavior Core Facility. To examine the disruption of GABAB receptor expression in the mutant mice injected with AAV vectors, immunohistochemistry and confocal imaging analysis in the Imaging Facility will be used.

Congratulations to the recipients of this year's Pilot awards! Interested in submitting an application for the forthcoming cycle of awards? Letters of intent are due by Wednesday, March 31st. Please check the CNR website for dates and more detailed information. All questions concerning the awards can be directed to the Center Administrator.

Core Awards 2009
In 2007 the CNR started a new award mechanism - the Core Award - which is also meant to support neuroscientists in their efforts to obtain sufficient evidence to prepare data for a grant submission. The major differences between the Core and Pilot Awards are as follows:
  •    » The Core Awards can ONLY be used to pay for core services at the CNR and/or at the Tufts Molecular Facility (mass spectrometry).
  •    » The Core Awards are smaller and limited to $3,000 per recipient
  •    » The Core Awards have a rolling deadline, i.e. researchers may apply any time during the year.

In 2009, Dr. Jun Xu was given a core award to support his research of the mediations of 5HT1b by alcohol-induced chromatin remodeling, hypo-acetylation of histones in particular, at the 5HT1b promoter sequence. Dr. Xu is working to determine the functional significance of histone acetylation on aggression by treating alcohol self-administering mice with trichostatin A (TSA), which specifically blocks histone deacetylation. Dr. Xu is using the CNR Behavior Core for testing, as well as the Genomics core (Affymetrix) to assess histone acetylation at the genome level using the Nimblegen mouse promoter arrays.

Dr. F. Rob Jackson was also awarded funds through the Core Award program in 2009. He is examining the interaction between micro(mi)RNAs and a defined RNA-binding protein (LARK) in the circadian regulation of protein translation. Expression profiling (RT-PCR and miRNA microarray) experiments will be carried out in the CNR Genomics Core, and the Imaging Core will be utilized as well to follow the expression of EGFP from translational reporter transgenes.

For more information on the core awards, please visit the CNR website.
 


Recent CNR Publications (selected list)
* please note that individuals outside of Tufts network may not be granted free access to the articles below.

Byrnes, E. M., Bridges, R. S., Scanlan, V. F., Babb, J. A., and Byrnes, J. J. (2007). Sensorimotor gating and dopamine function in postpartum rats. Neuropsychopharmacology 32: 1021-1031.

Cordeira, J. W., Frank, L., Sena-Esteves, M., Pothos, E. N., and Rios, M. (2-17-2010). Brain-derived neurotrophic factor regulates hedonic feeding by acting on the mesolimbic dopamine system. Journal of Neuroscience 30: 2533-2541.

Draper, I., Kurshan, P. T., McBride, E., Jackson, F. R., and Kopin, A. S. (2-15-2007). Locomotor activity is regulated lay D2-like receptors in Drosophila: An anatomic and functional analysis. Developmental Neurobiology 67: 378-393.

Graham, C. E., Basappa, J., and Vetter, D. E. (1-28-2010). A corticotropin-releasing factor system expressed in the cochlea modulates hearing sensitivity and protects against noise-induced hearing loss. Neurobiol Dis. (Epub ahead of print, PMID: 20109547.

Liu, W., Zscheppang, K., Murray, S., Nielsen, H.C., Dammann, C.E. (Jul 2007). The ErbB4 receptor in fetal rat lung fibroblasts and epithelial type II cells. Biochim Biophys Acta. 1772(7):737-47.

Murthy, V., Taranda, J., Elgoyhen, A. B., and Vetter, D. E. (2009). Activity of nAChRs containing alpha9 subunits modulates synapse stabilization via bidirectional signaling programs. Developmental Neurobiology 69: 931-949.

Olsen, D. P., Dunlap, K., and Jacob, M. H. (2007). Kainate receptors and RNA editing in cholinergic neurons. Journal of Neurochemistry 101: 327-341.

Suh, J. and Jackson, F.R. (8-2-2007). Drosophila Ebony activity is required in glia for the circadian regulation of locomotor activity. Neuron 55 (3): 435-447.

Turcan, S., Slonim, D. K., and Vetter, D. E. (2-4-2010). Lack of nAChR Activity Depresses Cochlear Maturation and Up-Regulates GABA System Components: Temporal Profiling of Gene Expression in alpha9 Null Mice. PLos One 5: e9058.

Zscheppang K., Liu, W., Volpe, M.V., Nielsen, H.C., and Dammann, C.E. (Aug 2007). ErbB4 regulates fetal surfactant phospholipid synthesis in primary fetal rat type II cells. Am J Physiol Lung Cell Mol Physiol. 293(2):L429-35.

 


Contact Us

We welcome your comments, suggestions and questions regarding our newsletter! Please direct them to the Center Administrator.

CNR Directors
Dr. F. Rob Jackson
Director and Principal Investigator, CNR
Co-Director, Imaging Core
Stearns 329
617-636-6752
rob.jackson@tufts.edu
Dr. Michele Jacob
Co-Director, Imaging Core
Stearns 327
617-636-2429
michele.jacob@tufts.edu
Dr. Alan Kopin
Director, Genomics Core
Tupper 7
617-636-4834
akopin@tufts-nemc.org
 
Dr. Kathleen Dunlap
Director, Electrophysiology Core
Stearns 209
617-636-4010
kathleen.dunlap@tufts.edu
Dr. Klaus Miczek
Director, Behavior Core
Bacon Hall 102C (Medford)
617-627-3414
klaus.miczek@tufts.edu
 


CNR Core Personnel
Dr. Alenka Lovy-Wheeler
Manager, Imaging Facility
Stearns 207D
617-636-3795
alenka.lovy_wheeler@tufts.edu
Dr. Lakshmanan Iyer
Senior Manager, Genomics Core
Stearns 331
617-636-0329
lax.iyer@tufts.edu
Christopher Parkin
Bioinformaticist, Genomics Core
Stearns 328B
617-636-3623
christopher.parkin@tufts.edu
 
Dr. Shui-Ying Ng
Epifluorescence Microscopy Technician, Imaging Core
Arnold 305
617-636-3680
shui-ying.ng@tufts.edu
Dr. Chuang Du
Manager, Electrophysiology Core
Arnold 106b
617-636-6988
chuang.du@tufts.edu
Dr. Isabel Quadros
Manager, Behavior Core
Stearns 331
617-636-2490
isabel.quadros@tufts.edu
 
Megan W. Morgove
Center Administrator
Stearns 301
617-636-3624
megan.morgove@tufts.edu
   
 
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