1.Evolved not engineered: a systemsneurobiology
Bjrn Brembs
http://brembs.net
Freie Universitt Berlin, Institut fr Biologie Neurobiologie
Knigin-Luise Str. 28/30, 14195 Berlin, Germany.
Email: bjoern@brembs.net, phone: +49 (0)30 838 55050, fax: +49 (0)30 838 55455

2. Systems Biology
Bjrn Brembs, Freie Universitt Berlin, http://brembs.net
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Lee Hoods Automobile Paradigm
3. Gene Networks
Engineeredsystemsentailstablenetworkinteractions
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M.Costanzo et al.,Science327, 425-431 (2010)
4. Clockwork
Are Biological OrganismsEngineered?
5. How Stable Are Gene Interactions?
Phenotypeofthetemperature sensitive Syntaxin-1A (Syx1A) mutant:
Bjrn Brembs, Freie Universitt Berlin, http://brembs.net
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% standing
time
39C
25C
van Swinderen & Greenspan (2005)
6. Screening forsyxSuppressors
Isolating mutants extending the time standing at 39C over Syx1A
Bjrn Brembs, Freie Universitt Berlin, Institut fr Biologie - Neurobiologie. http://brembs.net
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Syx-
+
% standing
Syx-Sup
+ +
time at 39C
van Swinderen & Greenspan (2005)
7. Quantifying Gene Interactions
In thewildtypebackground
Bjrn Brembs, Freie Universitt Berlin, Institut fr Biologie - Neurobiologie. http://brembs.net
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expected
observed
Sup1Sup2
+ +
Sup1Sup2
+ +
and in theSyx-background
Syx-
+
% standing
Syx-
+
time at 39C
van Swinderen & Greenspan (2005)
8. A Gene Interaction Matrix
The genematrix in WT background
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The genematrix in Syx-background
previous interaction
positive interaction
missing interaction
negative interaction
reversed sign
new interaction
9. 10. Octopamine and Insect Flight
OA isthe relevant amine
Flies without OA fly well
Flies withblocked TA receptorsfly well
Flies without OA and TA do notfly well
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Brembs et al. (2007)
11. Robustness by Degeneracy
30% ofmurineandupto 50% ofyeastgene knock-outsarewithoutphenotype.
redundant
degenerate
12. Neural Networks
Do neuralnetworksbehavelikegenenetworks?
13. General Brain Function
14. Input-Output
I reacttoexternalstimuli, therefore I am?
15. SquidEscapeBehavior
16. Loligogiantaxons
www.mbl.edu
Electrode in giantaxon
17. Fish C-start Response
18. TentacleSnakespredictfishresponse
19. Fly Escape Response
20. PaintedRedstartspredictflyresponse
21. Predictability
Being predictable is not evolutionary stable
22. DegreesofPredictability
Evoked
Fixed stimulus/responseatfixedlatency
e.g. reflex
Mixed
Complexstimuli/variable actions
Behavioralset
Endogenousevokedresponses
Closedloop
Predictability
Spontaneous
Activityindependentofsensoryinput
e.g. exploration
Stimulus-responsecoupling
23. Degreesof Efficiency
Evoked
Fixed stimulus/responseatfixedlatency
e.g. reflex
/ Efficiency
Mixed
Complexstimuli/variable actions
Behavioralset
Endogenousevokedresponses
Closedloop
Predictability
Spontaneous
Activityindependentofsensoryinput
e.g. exploration
Stimulus-responsecoupling
24. Psychological Challenge
Response
Action
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25. Ecological Challenge
Exploitation
Exploration
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26. Evolutionary Challenge
Optimality
Flexibility
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27. Reafferent Feedback
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28. General brainfunction
Action Outcome Evaluation
29. Drosophila Turning
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Behavioralvariability in a constantstimulussituation:
Actions, not responses
30. Drosophila Turning
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Behavioralvariability in a constantstimulussituation:
Actions, not responses
31. Choice or Noise?
Decisionsor just noise in complexstimulus-responsesystems?
32. Choice or Noise?
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Maye et al. (2007) PLoSOne
Geometric Random Inner Products: GRIP
33. Choice or Noise?
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correlation
nonlinearity
Maye et al. (2007) PLoSOne
Nonlinear (choice)
Linear/stochastic (noise)
34. Choice or Noise?
Maye et al. (2007) PLoSOne
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35. Choice or Noise?
Nonlineardecision-makingsystem underlies spontaneity in flies
36. spontaneity
Whatarethefunctionsofspontaneousbehavioralvariability?
37. Pursuit-evasioncontests& competition (courtship, predator-prey, territoriality, chess, sports etc.)
38. Exploration (find thathiddenresourceyouwouldotherwisenever find.)
39. Detectionofre-afferent signals in thesensorystream (trytotickleyourself!) -> operant behavior/learning
40. Reafferent Feedback
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41. BehavioralVariability
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42. BehavioralOutcomes
operant
self
classical
world
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43. Operant conditioning
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44. Action - Outcome Evaluation
Brembs & Plendl (2008) CurrentBiology
rut-AC dependentSynapticPlasticity
Protein Kinase C
world
self
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45. Conservation
PKC but not rut-AC involved in Aplysiaself-learning
Aplysiacalifornica
F. Lorenzetti, D. Baxter, J. Byrne (2008): Neuron 59, 815-828
46. Action Outcome Evaluation
FoxP2
Language learning
47. 13.07.2010
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FoxPisNecessaryforSelf-Learning
48. PKC/FoxPrequiredforSelf-Learning
FoxP
PKC
Not required
Not required
Required
Required
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49. Two Components
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50. Multiple Memories
Whyhavemorethanonelearningsystem?
51. Evolutionary Dilemma
Exploitation
Exploration
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52. Multiple Learning Systems
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53. From Exploration toExploitation
Brembs (2009)
54. Reciprocal, Hierarchical Interactions
Facilitation:
Learning-by-doing
Inhibition:
Regulateshabitformation/generalization :
Exploitation
Exploration
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55. General FLY brainfunction
Action Outcome Evaluation
56. Gspr Jkely
Ancestral: Stimulus-Response?
Max Planck Institute for Developmental Biology
Phototaxis
Polychaete: Platynereisdumerilii
57. Ancestral: Stimulus-Response?
Phototaxis
Stimulus Response
Sensoryneurons Ciliatedcells
Polychaete: Platynereisdumerilii
58. Phototaxis: Stimulus-Response?
Behavior (action)
Stimuli inhibitormodulateaction
Result: Phototaxis
G Jkelyet al.Nature456, 395-399 (2008) doi:10.1038/nature07590
59. Ancestral State
Ongoingactivitymodulatedbyexternalstimuli
60. The Default Mode Network
The limitingfactor in theevolutionofbrainsize was energysupply
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61. The Default Mode Network
The limitingfactor in theevolutionofbrainsize was energysupply
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The additional energyburdenassociatedwith [] theenvironmentmaybeaslittleas .5-1.0% ofthe total energybudget.
Marcus Raichle (2006): Science314, p1249
62. Human State
Ongoingactivitymodulatedbyexternalstimuli
63. The Engineering Approach toBiology
Can beseenasanalogoustoNewtonianMechanics in physics
64. Standing on the shoulder of giants
Teachers & Collaborators
Flight performance:
Carsten Duch
Frauke Christiansen
Jochen Pflger
Fly learning:
Wolfgang Plendl
Jan Wiener
Natalie Hempel de Ibarra
Troy Zars
Reinhard Wolf
Martin Heisenberg
Teachers:

Martin Heisenberg

65. Jack Byrne 66. Randolf Menzel 67. Bernard Balleine 68. Ralph Greenspan 69. George Sugihara 70. Bill Kristan 71. David Glanzman 72. Eric Kandel 73. Jochen Pflger 74. Ed Kravitz 75. Richard Morris 76. Hans-Peter Lipp 77. David Wolfer 78. Barry Keverne 79. KlaudeWeiss 80. Cathy RankinAplysiaconditioning:
Fred Lorenzetti
Riccardo Mozzachiodi
VuHyun
Elizabeth Wilkinson
Fredy Reyes
Jack Byrne
Aplysiaimaging:
Quentin Gaudry
William Kristan
Fly spontaneity:
Alexander Maye
ZacHsieh
George Sugihara
Fly aggression:
Britta Wittek
Andrea Baier
Ed Kravitz
Fly attention:
Bruno van Swinderen