integrative study of neural systems and behavior
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Integrative Study of
Neural Systems and Behavior
Hans A. Hofmann
The University of Texas at Austin
Center for Computational Biology and Bioinformatics
Department of Integrative Biology
Institute for Cellular & Molecular Biology
Institute for Neuroscience
http://cichlid.biosci.utexas.edu/
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Could a neuroscientist understand a microprocessor?
Jonas & Kording, 2016
(1) There exist complex information-processing systems which are composed of many interconnected discrete "units“
(2) For all their differences, brains and microprocessors are examples of such systems
(3) We need analytical and measurement techniques to understand these systems
(4) Neuroscientists have come up with many such approaches
(5) If these approaches are useful at figuring out the systems described in (1), then they ought to be informative when applied to any of those systems
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We Actually Understand the MOS 6502 Processor
Jonas & Kording, 2016
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Behavioral Phenotypes of a Microprocessor MOS 6502
Jonas & Kording, 2016
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Jonas & Kording, 2016
Reconstructing the Connectome
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Jonas & Kording, 2016
Lesioning Transistors to Understand Function
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Jonas & Kording, 2016
Spike Statistics
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Jonas & Kording, 2016
Quantifying Tuning Curves to Understand Function
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Jonas & Kording, 2016
Measuring Local Field Potentials to Understand Network Properties
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Jonas & Kording, 2016
Understanding Functional Connectivity
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Jonas & Kording, 2016
Whole Brain Recording to Obtain ALL the Data!
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Integrative Study of Neural Systems & Behavior
Core Competencies* Example Application
quantification of behavior
field methods, behavioral observations, natural history
knowing your animal, ethograms
ecology/evolution ultimate causes, environmental determinants of behavior, measuring fitness
putting research questions in broader biological context
mathematical theory game theory, evolutionary simulations
process based models of evolutionary and behavioral dynamics
statistics Bayesian analysis hierarchical models
computational methods bioinformatics, machine learning tracking, feature extraction, handling genomic data
genetics/genomics functional genomics, gene expression
genotyping, gene function, gene manipulation
physiology/neurobiology endocrinology, electrophysiology characterizing neural/molecular mechanism
Table 1. Core competencies for the integrative study of NS&B.
http://www.nsf.gov/div/index.jsp?div=IOS
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http://www.slideshare.net/mmehlmann/blind-menelephant
The Blind Men and the Elephant
It was six men of Indostan
To learning much inclined,
Who went to see the Elephant
(Though all of them were blind),
That each by observation
Might satisfy his mind
[…]
So oft in theologic wars,
The disputants, I ween,
Rail on in utter ignorance
Of what each other mean,
And prate about an Elephant
Not one of them has seen!
John Godfrey Saxe (1816–1887)
If each had a candle and they went in
together the differences would disappear.
Rumi, 13th Century Persian poet and Sufi teacher
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-Integrating multiple technologies
-Meta-analyses of large-scale (public) data sets
-Working across disciplines
-Large-scale collaborations and/or centers
-…
What IS the “Integrative” Study of Brain and Behavior?
Practical Considerations
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-Pursuing two or more of “Tinbergen's Four Questions” in the same study
-Integrating across levels of biological organization
-Integrating across time scales
-Using a comparative/phylogenetic approach
-…
What IS the “Integrative” Study of Brain and Behavior?
Conceptual Approaches
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Function
Causation
Development
Evolution
Four Fundamental Questions of Biological Research
Niko Tinbergen
1973 Nobel Prize
“Tinbergen’s Four
Questions” (1963)
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-Pursuing two or more of “Tinbergen's Four Questions” in the same study
-Integrating across levels of biological organization
-Integrating across time scales
-Using a comparative/phylogenetic approach
-…
What IS the “Integrative” Study of Brain and Behavior?
Conceptual Approaches
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Gene Expression
Neural Circuits
Social Networks
Evolution
Integrating Across Levels of Biological Organization
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-Pursuing two or more of “Tinbergen's Four Questions” in the same study
-Integrating across levels of biological organization
-Integrating across time scales
-Using a comparative/phylogenetic approach
-…
What IS the “Integrative” Study of Brain and Behavior?
Conceptual Approaches
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Integration Across Time ScalesE
nvir
onm
ent/
Ph
eno
typ
e Modulation
Learning & Memory Formation
Generation S Generation XGeneration L Generation XL
“Epigenetic Plasticity”
Genomic imprinting
Maternal effects
Behavioral imprinting
Social learning/traditions
(Adaptive) Phenotypic Plasticity
Passive or active
Irreversible: Developmental Plasticity,
Polyphenisms
Reversible: Use-dependent changes, Memory,
Traits under behavioral/environmental control
Genetic Polymorphisms
Evolutionary Plasticity
Mutation
Selection & DriftTime
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-Pursuing two or more of “Tinbergen's Four Questions” in the same study
-Integrating across levels of biological organization
-Integrating across time scales
-Using a comparative/phylogenetic approach
-…
What IS the “Integrative” Study of Brain and Behavior?
Conceptual Approaches
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The Power of the Comparative Method
"Ought we, for instance, to begin by discussing each separate species - man,
lion, ox, and the like - taking each kind in hand independently of the rest, or
ought we rather to deal first with the attributes which they have in common in
virtue of some common element of their nature, and proceed from this as a
basis for the consideration of them separately?“Aristotle, Περὶ ζῴων μορίων, ca. 350 BC
"... we must learn to treat comparative data with the same respect as we would
treat experimental results ...“Maynard Smith & Holliday, 1979
Aristotle (384-322)
John Maynard Smith
(1920-2004)
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25
Using a Comparative/Phylogenetic Approach
Pollen AA & Hofmann HA, 2008, Brain, Behavior & Evolution 72:145
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19th Century Physiology: Comparative in Search of Generality
Logan CA (2002) J Hist Biol 35:329–363
Journal Pflügers Archiv du Bois Archiv
1885-1900: volumes, papers 45, 931 16, 402
Single species papers 64.6% 64.6%
Humans 24.4% 15.4%
Dogs 13% 19.1%
Rabbits 5.2% 6%
Frogs 12% 15.2%
Other 10% 8%
Multi-species papers 32% 33.6%
2 species >14% >17.2%
≥3 species ~18% ~16.4%
Species/volume 3-10 (mode = 6) 4-9 (mode = 6)
New species encounter rate 3.5 papers 4.5 papers
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What is a Model System?
From Wikipedia, the free encyclopedia
A model organism is a non-human species that is extensively studied to understand
particular biological phenomena, with the expectation that discoveries made in the organism model will
provide insight into the workings of other organisms.Model organisms are in vivo models and are widely used
to research human disease when human experimentation would be unfeasible or unethical. This strategy is
made possible by the common descent of all living organisms, and the conservation of metabolic and
developmental pathways and genetic material over the course of evolution.Studying model organisms can be
informative, but care must be taken when extrapolating from one organism to another.http://en.wikipedia.org/wiki/Model_organism
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Krogh’s Principle: Assumes Generality!
“For a large number of problems there will be some animal of choice, or a few such animals, on which it can be most conveniently studied.”
August Krogh (1874-1949)
Nobel Prize in Physiology
or Medicine 1920
Krogh A (1929) Science 70:200–204
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Lewis Carroll: The Hunting of the Snark
Lewis Carroll (1832 –
1898)
Lewis Carroll, 1879
“If your Snark be a Snark, that is right:
Fetch it home by all means—you may serve it with greens,
And it's handy for striking a light.
*******************
"But oh, beamish nephew, beware of the day,
If your Snark be a Boojum! For then
You will softly and suddenly vanish away,
And never be met with again!'”
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Frank Beach: The Snark is a Boojum!
Frank A. Beach (1911-
1988)
Founder of Behavioral
Neuroendocrinology
Beach FA. 1950. American Psychologist 5:115–124.
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Disparity in the Organisms Used in Studies of Social Behavior, Ecology, and Neurobiology
Taborsky, Hofmann et al. (2015) TINS 38:189-191
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Utilizing Many Systems Within a Comparative Framework
Phelps SM, Campbell P, Zheng D, Ophir AG. 2010.
Neuropharmacology 58:17–28.
Benefits:
- No single species is suitable to address all aspects of a question or (human) phenotype of interest
- Focus on a small number of distantly related species makes it impossible to generalize
- Evolutionary approaches and non-traditional models can illuminate the nature and origin of within-species variation
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http://www.slideshare.net/mmehlmann/blind-menelephant