Perspectives Section Tag

Optogenetics: A Vision of the Future of Neurology?

Fraser Brown, 3rd year Medical Student, University of Edinburgh, UK.

In 1979, Nobel laureate Francis Crick published a paper discussing progress in neuroscience. Describing the subject as “profoundly mysterious”, he speculated on new methods of investigating the brain, including the ability to inactivate one type of neuron whilst leaving the others “more or less unaltered” [1]. Crick is not alone; for years the mammalian brain has dumbfounded researchers [1,2]. In the human, a hundred billion neuronal parts and myriad connections lead to an interconnected system of a level of unparalleled complexity [3].


1. Crick F. H. C. Thinking about the brain. Sci. Am. 1979.

2. Deisseroth K. Controlling the brain with light. Sci Am. 2010 303(5):48-55.

3. Koch C, Laurent G. Complexity and the nervous system. Science. 1999 2;284(5411):96-8. DOI:10.1126/science.284.5411.96

4. Wittchen HU, Jacobi F, Rehm J, Gustavsson A, Svensson M, Jönsson B, Olesen J, Allgulander C, Alonso J, Faravelli C, Fratiglioni L, Jennum P, Lieb R,Maercker A, van Os J, Preisig M, Salvador-Carulla L, Simon R, Steinhausen HC. The size and burden of mental disorders and other disorders of the brain in Europe. Eur Neuropsychopharmacol. 2011 21(9):655-79. DOI:10.1016/j.euroneuro.2011.07.018

5. Williams S. C. P, Deisseroth K. Optogenetics. Proc. Natl. Acad. Sci. USA. 2013 110(41):16287 DOI:10.1073/pnas.1317033110

6. Harz H, Hegemann P. Rhodopsin-regulated calcium currents in Chlamydomonas. Nature 1991 351(6326):489–491. DOI:10.1038/351489a0

7. Boyden ES, Zhang F, Bamberg E, Nagel G, Deisseroth K (2005) Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci 8(9):1263–1268. DOI:10.1038/nn1525

8. Reiner A, Isacoff EY. The Brain Prize 2013: the optogenetics revolution. Trends Neurosci. 2013 Oct;36(10):557-60. DOI:10.1016/j.tins.2013.08.005

9. Tye KM, Prakash R, Kim S, Fenno LE, Grosenick L, Zarabi H, Thompson KR, Gradinaru V, Ramakrishnan C, Deisseroth K. Amygdala circuitry mediating reversible and bidirectional control of anxiety. Nature. 2011 17; 471(7338): 358–363 DOI:10.1038/nature09820

10. Tye KM, Deisseroth K. Optogenetic investigation of neural circuits underlying brain disease in animal models. Nat Rev Neurosci. 2012 20;13(4):251-66. DOI:10.1038/nrn3171

11. Gunaydin LA, Yizhar O, Berndt A, Sohal VS, Deisseroth K, Hegemann P. Ultrafast optogenetic control. Nat Neurosci. 2010 13(3):387-92. DOI:10.1038/nn.2495

12. Yizhar O, Fenno LE, Davidson TJ, Mogri M, Deisseroth K. Optogenetics in neural systems. Neuron. 2011 14;71(1):9-34. DOI:10.1016/j.neuron.2011.06.004

13. LaLumiere RT. A new technique for controlling the brain: optogenetics and its potential for use in research and the clinic. Brain Stimul. 2011 4(1):1-6. DOI:10.1016/j.brs.2010.09.009

14. Mandel RJ, Manfredsson FP, Foust KD, Rising A, Reimsnider S, Nash K, Burger C.Recombinant adeno-associated viral vectors as therapeutic agents to treat neurological disorders. Mol Ther. 2006 13(3):63-83. DOI:10.1016/j.ymthe.2005.11.009

15. Diester I, Kaufman MT, Mogri M, Pashaie R, Goo W, Yizhar O, Ramakrishnan C, Deisseroth K, Shenoy KV. An optogenetic toolbox designed for primates. Nat Neurosci. 2011 14(3):387-97. DOI:10.1038/nn.2749

16. González F, Boué S, Izpisúa Belmonte JC. Methods for making induced pluripotent stem cells: reprogramming à la carte. Nat Rev Genet. 2011 12(4):231-42. DOI:10.1038/nrg2937

17. Kravitz AV, Freeze BS, Parker PR, Kay K, Thwin MT, Deisseroth K, Kreitzer AC. Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry. Nature. 2010 29;466(7306):622-6. DOI:10.1038/nature09159

18. Gradinaru V, Mogri M, Thompson KR, Henderson JM, Deisseroth K. Optical deconstruction of parkinsonian neural circuitry. Science 2009;324:354-359. DOI:10.1126/science.1167093

19. SH Elsea, RE Lucas The mousetrap: what we can learn when the mouse model does not mimic the human disease. ILAR J 2002 43(2):66-79. DOI:10.1093/ilar.43.2.66

20. Dragunow M. The adult human brain in preclinical drug development. Nat. Rev. Drug Discov. 2008 7(8):659-66. DOI:10.1038/nrd2617

21. Takahashi K, Yamanaka S. Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors. Cell 2006 126(4):663–676 DOI:10.1016/j.cell.2006.07.024

22. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007 30;131(5):861-72. DOI:10.1016/j.cell.2007.11.019

23. Daley GQ. The Promise and Perils of Stem Cell Therapeutics. Cell Stem Cell 2012 10(6):740-9. DOI:10.1016/j.stem.2012.05.010

24. Merkle FT, Eggan K. Modeling Human Disease with Pluripotent Stem Cells: from Genome Association to Function. Cell Stem Cell 2013 6;12(6):656-68. DOI:10.1016/j.stem.2013.05.016

25. Ebert AD, Yu J, Rose FF Jr, Mattis VB, Lorson CL, Thomson JA, Svendsen CN. Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature 2009 15;457(7227):277-80. DOI:10.1038/nature07677

26. Serio A, Bilican B, Barmada SJ, Ando DM, Zhao C, Siller R, Burr K, Haghi G, Story D, Nishimura AL, Carrasco MA, Phatnani HP, Shum C, Wilmut I, Maniatis T, Shaw CE, Finkbeiner S, Chandran S. Astrocyte pathology and the absence of non-cell autonomy in an induced pluripotent stem cell model of TDP-43 proteinopathy. Proc. Natl. Acad. Sci. USA 2013 110(12):4697-702. DOI:10.1073/pnas.1300398110

27. Devine MJ, Ryten M, Vodicka P, Thomson AJ, Burdon T, Houlden H, Cavaleri F, Nagano M, Drummond NJ, Taanman JW, Schapira AH, Gwinn K, Hardy J, Lewis PA, Kunath T. 2011. Parkinson’s disease induced pluripotent stem cells with triplication of the α-synuclein locus. Nat Commun. 2011 23;2:440. DOI:10.1038/ncomms1453

28. Rashid ST, Corbineau S, Hannan N, Marciniak SJ, Miranda E, Alexander G, Huang-Doran I, Griffin J, Ahrlund-Richter L, Skepper J, Semple R, Weber A, Lomas DA, Vallier L. Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells. J Clin Invest. 2010 120(9):3127-36. DOI:10.1172/JCI43122

29. Marchetto MC, Brennand KJ, Boyer LF, Gage FH. Induced pluripotent stem cells (iPSCs) and neurological disease modeling: progress and promises. Hum Mol Genet. 2011 15;20(R2):R109-15 DOI:10.1093/hmg/ddr336

30. Trounson A, Shepard KA, DeWitt ND. Human disease modeling with induced pluripotent stem cells. Curr Opin Genet Dev. 2012 22(5):509-16. DOI:10.1016/j.gde.2012.07.004

31. Tønnesen J. Optogenetic cell control in experimental models of neurological disorders. Behav Brain Res. 2013 15;255:35-43. DOI:10.1016/j.bbr.2013.07.007

32. Demont-Guignard S, Benquet P, Gerber U, Biraben A, Martin B, Wendling F. Distinct hyperexcitability mechanisms underlie fast ripples and epileptic spikes. Ann Neurol. 2012 71(3):342-52. DOI:10.1002/ana.22610

33. Tønnesen J, Sørensen AT, Deisseroth K, Lundberg C, Kokaia M. Optogenetic control of epileptiform activity. Proc Natl Acad Sci U S A. 2009 21;106(29):12162-7. DOI:10.1073/pnas.0901915106

34. Krook-Magnuson E, Armstrong C, Oijala M, Soltesz I. On-demand optogenetic control of spontaneous seizures in temporal lobe epilepsy. Nat Commun. 2013 4:1376. DOI:10.1038/ncomms2376

35. de Boer HM, Mula M, Sander JW. The global burden and stigma of epilepsy. Epilepsy Behav. 2008 12(4):540-6. DOI:10.1016/j.yebeh.2007.12.019

36. Albert PR. Light up your life: Optogenetics for depression? J Psychiatry Neurosci. 2014 39(1):3-5. DOI:10.1503/jpn.130267

37. Busskamp V, Roska B. Optogenetic approaches to restoring visual function in retinitis pigmentosa. Curr Opin Neurobiol. 2011 21(6):942-6.2011 21(6):942-6. DOI:10.1016/j.conb.2011.06.001

38. Jacobson SG, Sumaroka A, Luo X, Cideciyan AV. Retinal optogenetic therapies: clinical criteria for candidacy. Clin Genet 2013 84: 175–182. DOI:10.1111/cge.12165

39. Lobo MK, Nestler EJ, Covington HE 3rd. Potential utility of optogenetics in the study of depression. Biol Psychiatry. 2012 15;71(12):1068-74. DOI:10.1016/j.biopsych.2011.12.026

40. Manfredsson FP, Bloom DC, Mandel RJ. Regulated protein expression for in vivo gene therapy for neurological disorders: progress, strategies, and issues. Neurobiol Dis. 2012 48(2):212-21. DOI:10.1016/j.nbd.2012.03.001

41. Kravitz AV, Freeze BS, Parker PR, Kay K, Thwin MT, Deisseroth K, Kreitzer AC.Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry. Nature. 2010 29;466(7306):622-6. DOI:10.1038/nature09159

42. Deisseroth K. Optogenetics. Nat Methods 2011 8:26–29. DOI:10.1038/nmeth.f.324

How to win friends and influence students: The role of student Psychiatry Societies in remedying recruitment problems

Neel Halder, Consultant Psychiatrist, Alpha Hospital, Buller Street, Bury, BL8 2BS. Senior Honorary Lecturer, School of Medicine, The University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Judith Harrison, FY2, Royal Surrey Hospital, Egerton Road, Guildford, Surrey, GU2 7XX, UK.

Improving recruitment numbers into psychiatry in the UK is recognised as an important issue in the field. One recent way of tackling the problem has been to set up Psychiatry societies for undergraduates within medical schools. Very little has been published about this ever-growing phenomenon. This article provides personal perspectives from undergraduate and postgraduate levels, taking into account ideas trialled in areas of the UK.


1. Brockington, I, & Mumford, D. Recruitment into psychiatry. Br J Psychiatry 2002; 180: 307-312. doi:10.1192/bjp.180.4.307

2. Royal College of Psychiatrists. Annual Census of Psychiatric Staffing 2001. Occasional Paper OP54. London: Royal College of Psychiatrists, 2002.

3. Brown N, Vascillas C, Oakley C. Recruiting Psychiatrists – a Sisyphean task? Psychiatr Bull 2009; 33: 390-392. doi:10.1192/pb.bp.108.024638

4. Rajagopal S, Rehill KS, Godfrey E. Psychiatry as a career choice compared with other specialties: a survey of medical students. Psychiatr Bull 2004; 28: 444-446. doi:10.1192/pb.28.12.444

5. Craddock N, Antebi D, Attenburrow M. Wake-up call for British psychiatry. Br J Psychiatry 2008; 193: 6-9. doi:10.1192/bjp.bp.108.053561

6. Eagles JM, Wilson S, Murdoch JM, Brown T. What impact to undergraduate experiences have upon recruitment into psychiatry? Psychiatr Bull 2007; 31: 70-72. doi:10.1192/pb.bp.106.010801

7. Burack JH, Irby DM, Carline JD, Ambrozy DM, Ellsbury KE, Stritter FT. A study of medical students’ speciality-choice pathways: trying on possible selves. Acad Medicine 1997; 72: 534-41.…

8. Layard R. (2006) The case for psychological treatment centres. BMJ 2006; 332:1030–1032.


10. Simmons M. “Speed Dating” for careers advice in Psychiatry. BMJ Careers Nov 2009.

A Resource Underused

Ryan Breslin, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0SP

Ryan Breslin discusses what the third sector can teach us about the management of chronic diseases


1. VODG 2010 Gain without pain; A VODG report on how the voluntary sector can save time and money.

2. NHSScotland 2010 The Healthcare Quality Strategy for NHSScotland. ISBN 9780755993239

3. Clifford & Backus 2010 Are big charities becoming increasingly dominant? Tracking charitable income growth 1997-2008 by initial size.

Living with incontinence

Katherine Cole, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0SP

Imagine being reluctant to go anywhere for fear of embarrassment at what your body might do. But your family needs food, so you put on a brave face and go to the shop down the road. You’ve been walking around the supermarket for ten minutes, enjoying browsing the special offers, when it begins: the feeling of warm dampness between your legs, gradually spreading downwards. You glance at the wet patch steadily growing across the front of your jeans. It’s happened again: another outing is ruined. You take off your jacket and tie it round your waist in an attempt to hide what’s going on.

Profile of a Clinical Geneticist: Dr Geoff Woods

Despina Fotiou, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0SP
Lizzy Day, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0SP

Dr Geoff Woods, a clinical geneticist splitting his time between the clinic at Addenbrookes and the laboratory in CIMR, answers our questions and talks about what being a clinical geneticist means, the future of the speciality, personalized genomics and his own current research work.

Surviving Cynical School

Katrina Stewart, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0SP

Starting Clinical School at a university like Cambridge, where the insides of a hospital are often unfamiliar to medical undergraduates, is a daunting and exciting process. A few months in, I am beginning to wonder if seeing pain and suffering on a daily basis has changed me more than I had imagined it would. Am I beginning to see someone I barely know as an obese smoker rather than a mother or sister? An alcoholic rather than a man in terrible pain? In short, am I becoming more cynical?


1. Woloschuk W, Harasym PH, Temple W. Attitude change during medical school: a cohort study. Med Educ. 2004 May;38(5):522-534.

2. Chen D, Lew R, Hershman W, Orlander J. A cross-sectional measurement of medical student empathy. J Gen Intern Med. 2007 Oct;22(10):1434-8.

3. Masson N, Lester H. The attitudes of medical students towards homeless people: does medical school make a difference? Med Educ. 2003 Oct;37(10):869-72.

4. Tsimtsiou Z, Kerasidou O, Efstathiou N, Papaharitou S, Hatzimouratidis K, Hatzichristou D. Medical students’ attitudes toward patient-centred care: a longitudinal survey. Med Educ. 2007 Feb;41(2):146-53.

That Friday feeling

Nathan Lawrence, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0SP

We’ve all been there, all looked at the timetable and seen those two dreaded words filling our Friday afternoon and felt our hearts sink as we resign ourselves to a stultifying 3 hour diatribe on numbers needed to treat and the role of a public health doctor.


1. Lengeler C. Insecticide-treated bed nets and curtains for preventing malaria. Cochrane Database of Systematic Reviews. 2004; 2:CD000363.

The Medical butterfly effect; how a discovery in a rare disease can have large effects elsewhere.

Sophie E M Raby, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Road, Cambridge, CB2 0SP

The study of rare diseases is incredibly common in scientific research. Scientists justify this by claiming that understanding these rare conditions can provide insight into common disorders.

However, since funding is limited and must be prioritized, is this really the case? Or are researchers simply stating this on grant applications to obtain funding in order to satisfy their own intellectual interests? In short, what are the arguments for and against the study of rare diseases?


1. Eurordis. 2005. “Rare Diseases: understanding this Public Health Priority”.…

2. Lippincott et al. 2003. National Organization for Rare Disorders. NORD Guide to Rare Disorders. Philadelphia.

3. Scheuner, M. et al. 2004. Contribution of Mendelian disorders to common chronic disease. Am J Med Genet C Semin Med Genet. 125C(1):50-65.

4. Kole A and Faurisson F. 2009. The Voice of 12,000 Patients: Experiences & Expectations of Rare Disease Patients on Diagnosis & Care in Europe.

5. Nennstiel-Ratzel, U. et al. 2005. Reduced incidence of severe metabolic crisis or death in children with medium chain acyl-CoA dehydrogenase deficiency homozygous for c.985A>G identified by neonatal screening. Mol Genet Metab 85;157-9.

6. Burls A. et al. 2005. Commissioning for rare diseases: view from the frontline. BMJ 331:1019-1021.

7. O’Rahilly S. et al. 2003. Minireview: Human Obesity – Lessons from Monogenic disorders. Endocrinology 144(9): 3757-3764.

8. European Parliament. 2005. Regulation (EC) No 141/2000 of the European Parliament and of the Council of December 16, 1999 on orphan medicinal products. Official Journal of the European Communities 43(L18): 1-5.…

9. McCabe C. et al. 2005. Orphan drugs and the NHS: should we value rarity? BMJ 331:1016-1019

10. Knudsen ES and Knudsen KE. 2006. Retinoblastoma tumor suppressor: where cancer meets the cell cycle. Exp Biol Med (Maywood). Jul;231(7):1271-81.

11. Sábado Alvarez C. 2008. Molecular biology of retinoblastoma. Clin Transl Oncol. Jul;10(7):389-94.

12. Wang W. 2007. Emergence of a DNA-damage response network consisting of Fanconi anaemia and BRCA proteins. Nature Reviews Genetics 8, 735-748.

13. Zdzienicka, MZ and Arwert, F. 2002. Breast cancer and Fanconi anaemia: what are the connections? Trends Mol Med. Oct;8(10):458-60.

14. Fong, PC. Et al. 2009. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. Jul 9;361(2):123-34.

15. Ashworth A. 2008. A synthetic Lethal Therapeutic Approach: Poly(ADP)Ribose Polymerase Inhibitors for the treatment of cancers deficient in DNA double-stand break repair. J Clin Oncol. 26:3785-3790.

16. Dlugosz, AA and Talpaz, M. 2009. Following the hedgehog to new cancer therapies. N Engl J Med. Sep 17;361(12):1202-5.

17. Rudin, CM. et al. 2009. Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449. N Engl J Med. Sep 17;361(12):1173-8.

18. Von Hoff, DD. et al.2009. Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med. Sep 17;361(12):1164-72.

19. Olive KP. et al. 2009. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science 324:1457-1461.

20. Brouwers, N. et al. 2008. Molecular genetics of Alzheimer’s disease: an update. Ann Med.40(8):562-83.

21. Talbot K. 2007 The study of rare diseases: butterfly collecting or an entrée to understanding common conditions? Pract Neurol;7:210-211.

22. Appleton, E. 1953. Science for it’s own sake. Bulletin of the Atomic scientists.

23. Check Hayden, E. 2009. Genomics shifts focus to rare diseases. Nature. Sep 24;461.7263:458.

The Future of General Surgery

Faye Begeti, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0SP

“General surgeons are not what they used to be many years ago.”

This is a phrase I have heard multiple times emanating from nostalgic retired surgeons leading anatomy demonstrations in Cambridge University, always followed by stories of the heroic diversity of operations they performed and how time has changed this; and, albeit anecdotal, it is a perfect illustration of how general surgery has changed over the course of a few generations.


1. The Royal College of Surgeons of England. The surgical workforce: 2009 update.…

2. Di Carlo A, Andtbacka RH, Shrier I, Belliveau P, Trudel JL, Stein BL. The value of specialization—is there an outcome difference in the management of fistulas complicating diverticulitis. Diseases of the Colon & Rectum. 2001; 44(10):1456-1463.

3. Anwar S, Fraser S, Hill J. Surgical specialization and training – its relation to clinical outcome for colorectal cancer surgery. Journal of Evaluation in Clinical Practice. 2010.

4. Bachmann MO, Alderson D, Peters TJ, Bedford C, Edwards D, Wotton S, et al. Influence of specialization on the management and outcome of patients with pancreatic cancer. The British Journal of Surgery. 2003; 90(2):171-7.

5. Goodwin H. Litigation and surgical practice in the UK. The British Journal of Surgery. 2000; 87(8):977-9.

6. Bland KI, Isaacs G. Contemporary trends in student selection of medical specialties: the potential impact on general surgery. Archives of Surgery. 2002; 137(3):259-67.

7. Barshes NR, Vavra AK, Miller A, Brunicardi FC, Goss JA, Sweeney JF. General surgery as a career: a contemporary review of factors central to medical student specialty choice. Journal of the American College of Surgeons. 2004; 199(5):792-9.

8. Fernandez-Cruz L. General Surgery as Education, Not Specialization. Annals of Surgery. 2004; 240(6):932-938.

9. Dodson TF, Webb AL. Why do residents leave general surgery? The hidden problem in today’s programs. Current Surgery. 2005; 62(1):128-31.

10. Skillman J. The future of breast surgery: a new subspecialty of oncoplastic breast surgeons? Breast. 2003; 12(3):161-162.

11. Rainsbury RM. Training and skills for breast surgeons in the new millennium. ANZ Journal of Surgery. 2003; 73(7):511-6.

Drawing Naked Bodies

Kathy Liu, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Road, Cambridge, CB2 0SP

Imagine a naked 50 year old man. Trust me here.

Do you feel repulsed or curious?
Offended or appreciative?
Embarrassed or inspired?


1. Price-Kuehne, FE. 2010. Life Drawing for Medical Students. Student BMJ. 18:c1567

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