Bamford Laboratory

Postdoctoral Research Fellow

A position is available from July, 2008 in Neurology for an experienced and self-motivated post-doctoral fellow. The successful applicant will conduct electrophysiology research in striatal synaptic plasticity at the University of Washington, Seattle. A proven track record of experience performing whole-cell patch clamp recordings in brain slices is essential. The fellow will expand their skills by integrating optical, behavioral and electrophysiological recordings to determine the effect of repeated psychostimulants on corticostriatal activity in the dorsal and ventral striatum.

Candidates must have an MD or a PhD in biological sciences. Applications should include a cover letter describing research interests and past accomplishments, curriculum vita, bibliography and the names of 3 references. Strong analytical, writing, communication (in English) and problem solving skills are desired.

To apply, please send materials to:

Nigel S. Bamford
University of Washington
Dept. Neurology
Box 356465
1959 NE Pacific Street
Seattle, WA 98195
Email: This email address is being protected from spambots. You need JavaScript enabled to view it.

 

Summary of Proposed Research Project

The basal ganglia play an important role in habit formation and substance dependence. Excitatory glutamatergic projections from the cerebral cortex innervate the basal ganglia at the striatal medium spiny neuron, which also receives modulatory dopamine projections from midbrain nuclei as well as cholinergic inputs from tonically activated striatal interneurons. Psychostimulants and other drugs of abuse are known to produce alterations in these neurotransmitters, suggesting their implicit involvement in the synaptic mechanisms underlying dependence.

The Bamford laboratory has shown that dopamine depresses the release of glutamate from a subset of cortical terminals, providing filtering of cortical information to the striatum. Repeated use of psychostimulants in mice prevents striatal filtering by producing a chronic striatal depression in withdrawal that is renormalized by drug reinstatement. This effect is dose dependent, long lasting (>140 days) and is dependent on a new D1 receptor effect seen only in animals with previous psychostimulant experience. During withdrawal, a psychostimulant challenge produces a paradoxical increase in glutamate release by activating cholinergic-releasing interneurons. These mechanisms extend to locomotor sensitization and drug intake escalation – both hallmarks of addiction.

The Bamford laboratory offers students and fellows a unique opportunity to determine how changes in striatal synapses might produce alterations in animal behavior. The Bamford laboratory uses a combination of behavioral, optical and electrophysiological experiments to determine the effects of repeated psychostimulants on striatal function. Students can utilize a newly developed imaging technique that allows direct visualization of presynaptic release from cortical projections in murine striatal slice preparations. These optical studies can be integrated with whole-cell patch clamp recordings to delineate the characteristics of the corticostriatal pathway and the effects of dopamine transmission at the striatal medium spiny neuron. In vivo manipulations of transgenic and wild-type mice will provide models with which to investigate synaptic plasticity that occurs following repeated use of psychostimulants. The outcome of these investigations will demonstrate how alterations in dopamine release produce corticostriatal plasticity, show mechanistically how aberrant striatal excitation might lead to certain animal behaviors, and will provide further insights into pharmacological alternatives for the treatment of addiction.

Bamford Laboratory

People

nigel bamfordNigel S. Bamford

Principal Investigator
Assistant Professor of Neurology, Pediatrics and Psychology
Office: (206) 616-4150
This email address is being protected from spambots. You need JavaScript enabled to view it.
Education: University of Utah, Columbia College of Physicians and Surgeons

 

 

ian bamfordIan J. Bamford

Laboratory Artist
12-19-00 - present
Education: Mustard Seed, Somerset Elementary

Bamford Laboratory

Graduates

anitaAnita Bhansali, BA
Medical Student, University of Washington
06-01-2007 to 02-01-2008

Project Title: Activation of striatal cholinergic interneurons

Education: Johns Hopkins University, University of Washington

Selected Publications: Dopamine Regulation in the ventral striatum. In Preparation.

 

hanen

Whitney Hanen, BA
Undergraduate in Biology, University of Washington
09/01/06 – 06/01/07

Project Title:
Psychostimulant-induced locomotor sensitization

Education:
University of Washington

Selected Publications: Neuron. 2004. 58 (1): 89-103.

 

joyceJohn Joyce, MS
Research Technician
07/1/02 - 07/01/06

Education:
University of Connecticut

Selected Publications:

Neuron. 2008. 58 (1): 89-103.

Ann Neurol. 2006. 60(S10):S139

Ann Neurol. 2005. 60(S10):S139

Ann Neurol. 2005. 58 (S9) S81.

Society for Neuroscience Abstr. 2005. 1030.11

Ann Neurol. 2004. 56 (S8):S85.

J Neurosci. 2004. 24, 9541-52.

 

Tushar Kumar, MD
Medical Student Research Project, University of Washington
06/01/05– 09/01/05

Project Title: Activation of striatal cholinergic interneurons

Education: University of Washington

 

singhNamita Singh, MD
Medical Student Research Project, UCLA
06/01/04 – 09/01/04

Project Title: Activation of striatal cholinergic interneurons

Education: UCLA

Selected Publications: Society for Neuroscience Abstr. 2005. 1030.11

 

erbe

Jeff Erbe, BA
Student Intern Project
06-01-03 to 09-01-03


Project Title: Activation of striatal cholinergic interneurons

Education: Kalamazoo, Cornell

Selected Publications: Society for Neuroscience Abstr. 2005. 1030.11

 

deverDennis Dever, BA
Doctoral Candidate, University of Washington
08-01-06 to 2010

Project Title: Presynaptic regulation in the Nucleus Accumbens

Education: University of Maryland, University of Washington

Selected Publications: Dopamine Regulation in the ventral striatum. In Preparation.

 

loweJanet Lowe, PhD
Postdoctoral Fellow
12-01-07 to 2010

Project Title: Presynaptic Regulation of Striatal Excitation

Education: Cornell, University of Washington

Selected Publications: Dopamine Regulation in the ventral striatum. In Preparation.

 

ludwickLauren Ludwick
Undergraduate Biology, University of Washington
02-01-07 to 2010

Project Title: The behavioral effects of in utero cocaine exposure

 

scarlisChristine Scarlis, BA
Premedical, University of Washington
06-01-06 to 2010

Project Title: Behavioral sensitization and the behavioral effects of gestational cocaine exposure

Education: McGill, University of Washington

Selected Publications:
Neuron. 2008. 58 (1): 89-103.
Ann Neurol. 2007. 62(S11):S95-S97
Ann Neurol. 2007. 62(S11):S105-S107

 

towneJessica Towne, BS
Post-graduate volunteer
02-01-07 to 2010

Project Title: Electrophysiology and behavior

Education: Grand Valley State University, Allendale, MI

Selected Publications: Dopamine Regulation in the ventral striatum. In Preparation.

Bamford Laboratory

Selected Publications

  1. Wang W, Darvas M, Storey GP, Bamford IJ, Palmiter RD, Bamford NS*.  (2013)
    Acetylcholine Encodes Long-lasting Presynaptic Plasticity at Glutamatergic Synapses in the Dorsal Striatum after Repeated Amphetamine Exposure. Journal of Neuroscience. 33(25)10405-26. PMC3766752.
  2. Wang W, Nitulescu I, Lemos JC, Lewis JS, Bamford IJ, Posielski NM, Storey GP, Phillips PEM, Bamford NS*. (2012) Over-inhibition of Corticostriatal Activity following Prenatal Cocaine Exposure. Annals of Neurology. 73(3):355-69. PMC3766752.
  3. Quintana A, Sanz E, Wang W, Storey GP, Guler AD, Wanat MJ, Roller BA, La Torre A, McKnight GS, Bamford NS, Palmiter RD*. (2012) Lack of Gpr88 Regulates Medium spiny Neuron Activity and Facilitates Motor and Cue-dependent behaviors. Nature Neuroscience. 15(11)1547-55. PMC3483418. See comments on this research in:
    Nat Neurosci 2008. 58:6-7 2012.15(11): 1469-70.
  4. Wang W, Dever D, Lowe J, Storey GP, Bhansali A, Eck EK, Nitulescu I, Weimer J, Bamford NS*. (2012) Regulation of Prefrontal Excitatory Neurotransmission by Dopamine in the Nucleus Accumbens Core. Journal of Physiology. 590(16)3743-69. PMC3476631.
  5. Fraser CD, Jaquiss RDB, Rosenthal DN, Humpl T, Canter CE, Blackstone EH, Naftel DC, Ichord RN, Bomgaars L, Tweddell JS, Massicotte P, Turrentine MW, Cohen GA, Devaney EJ, Pearce FB, Carberry KE, Kroslowitz R, Almond CS, for the Berlin Heart Study Investigators. (2012)  Prospective Trial of a Pediatric Ventricular Assist Device. New England Journal of Medicine. 367:532-41. Bamford was a Berlin Heart study investigator.
  6. Yue M, Sulzer D, Bamford NS*.  (2011)  Imaging Presynaptic Exocytosis in Corticostriatal Slices. Methods Molecular Biology. 2011;793:363-76. doi: 10.1007/978-1-61779-328-8_24.
  7. Parker JG, Wanat MJ, Soden ME, Ahmad K, Zweifel LS, Bamford NS, Palmiter RD*. (2011) Attenuating GABAA Receptor Signaling in Dopamine Neurons Selectively Enhances Reward Learning and Alters Risk Preference in Mice. Journal of Neuroscience. 31(47):17103-12. PMC3235504.
  8. Beutler LR, Wanat MJ, Quintana A, Sanz E, Bamford NS, Zweifel LS, Palmiter RD*. (2011) Balanced NMDA receptor activity in dopamine D1 receptor (D1R)- and D2R-expressing medium spiny neurons is required for amphetamine sensitization. PNAS. 108(10):4206-11. PMC3054029.
  9. Joshi PR, Wu N-P, André VM, Cummings D, Cepeda C, Joyce JA, Carroll JB, Leavitt BR, Hayden MR, Levine MS, Bamford NS*. (2009) Age-dependent alterations of corticostriatal activity in the YAC128 mouse model of Huntington Disease. Journal of Neuroscience. 29(8):2414-2427. PMC2670193.
  10. Bamford NS*, Robinett SA, Otto RK, Gospe SM. (2009) Neuromuscular Hip Dysplasia in Charcot Marie Tooth Disease Type 1A. Developmental Medicine and Child Neurology. 51(5):408-11.
  11. Bamford NS*, Zhang H, Joyce JA, Scarlis CA, Hanan W, Wu N-P, André VM, Cohen R, Cepeda C, Levine MS, Harleton E, Sulzer D. (2008) Repeated exposure to methamphetamine causes long-lasting presynaptic corticostriatal depression that is renormalized with drug readministration. Neuron. 58 (1): 89-103. PMC2394729. Featured Article in Neuron. See Comments on this research in:
    • Neuron 2008. 58:6-7
    • Nature Reviews Neuroscience 2008. 9:409
    • JAMA 2008. 20:2379-2379.
  12. Bamford NS*, Robinson S, Palmiter RD, Joyce JA, Moore C, Meshul CK. (2004) Dopamine modulates release from corticostriatal terminals. Journal of Neuroscience. 24:9541-9552. PMID: 15509741.
  13. Bamford NS, Zhang H, Schmitz Y, Wu N-P, Cepeda C, Levine MS, Schmauss C, Zakharenko SS, Zablow L, Sulzer S*. (2004) Heterosynaptic dopamine neurotransmission selects sets of corticostriatal terminals. Neuron 42:653-663. PMID: 15157425. Featured Article in Neuron. See Comments on this research in: Neuron 2004. 42: 522-4
  14. Bamford NS*, Trojaborg W, De Vivo DC. (2002) Congenital Guillain-Barré syndrome associated with maternal inflammatory bowel disease is responsive to intravenous immunoglobulin. European Journal of Paediatric Neurology. 6(2):115-119. PMID:11995958.
  15. Shayegani A*, Odel JG, Kazim M, Hall LS, Bamford NS, Schubert H. (1996) Varicella-Zoster Virus Retrobulbar Optic Neuritis in a Patient with Human Immunodeficiency Virus. Am J Ophthal. 122(4):586-588.

 

Selected Book Chapters

  1. Yue M, Sulzer D, Bamford NS*. (2011) Imaging Presynaptic Exocytosis in Corticostriatal Slices. In: Methods in Molecular Biology. Volume: 793. Edited by H. Kawamata and G. Manfredi. Springer. p363-376
  2. Cepeda, C*, Bamford NS, Levine MS. (2010) Alterations in Striatal Synaptic Function in Huntington’s and Parkinson’s Diseases. In: Handbook of Basal Ganglia Structure and Function, a Decade of Progress. Edited by H. Steiner and K. Tseng. Elsevier. p607-623.
  3. Bamford NS*, Cepeda, C. (2009) The Corticostriatal Pathway in Parkinson’s Disease. In: Cortico-subcortical Dynamics in Parkinson’s Disease. Editor: Kuei Y. Tseng, Humana Press & Springer Editorials. p87-104.
  1. Overview
  2. Welcome
  3. Information