“Levels of Analysis in Behavioral Neuroscience” Ethan Gahtan Associate Professor of Psychology Adjunct Professor of Biology Humboldt State University BSS room 122 eg51@

Outline My research on sensorimotor circuits in zebrafish larvae Levels of analysis in behavioral neuroscience Focus on circuit level and connectomes… worth the effort? Take home messages

About Ethan Gahtan Education University of Minnesota, PhD 1999. Cognitive and Biological Psychology Research- neural mechanisms of adaptive behavior MA : Common reward systems in drug addiction PhD: Brain inflammation as a cause of cognitive deficits in AD Post doc and current: hindbrain circuits mediating sensorimotor behavior Teaching Behavioral neuroscience I (Fall) and II (Spring, with lab) Evolutionary psychology Psychopharmacology Cellular neuroscience Social Neuroscience

ON SABBATICAL!

Current research: Topographical mapping in sensorimotor circuits The point of this example: The topography of the retina must be mapped onto motor systems Raises the question: How do neural circuits do this?

Somatotopic maps in human cortex Primary sensory cortex Primary motor cortex Ascending from body Descending to muscles

Descending sensorimotor pathways in human and fish brain

–EO Wilson / Krogh’s Principle “For every problem in biology, there exists a species ideal for its solution.” –EO Wilson / Krogh’s Principle Zebrafish larvae have good characteristics for a model species: Homology--------------------------------- Are vertebrates Genetically tractable-------------------Forward/reverse genetics Accessibility-------------------------------Transparent Rapid development----------------------Autonomous hunters by day 5 Simplicity ----------------------------------relatively few cells overall Manipulation----------------------------genetic, surgical, optical, environmental, etc etc Morally permissive----------------------fish, but still vertebrates Cost and ease of use--------------------unsurpassed for vertebrates www.nc3rs.org.uk

Individually identifiable neurons. Zebrafish in behavioral neuroscience research Individually identifiable neurons. The ‘same’ neuron can be identified across animals The only vertebrate where entire neural systems are composed of identifiable neurons!

Reticulospinal (RS) neurons – a focus of my research. RS neurons form the main pathway from brain to spinal cord. Information flow in sensorimotor circuits: Sensory neurons  RS neurons  Spinal cord neurons Many neurons in these pathways are individually identifiable in zebrafish Identifiable neurons means synaptic connections can be mapped with cellular level precision Question: Are RS neurons somatotopically organized?

Strategy for identifying synapses onto RS neurons: Anatomical tracing Targeted stimulation

“Levels of Analysis in Behavioral Neuroscience” But first, what exactly is behavioral neuroscience?

Behavior Biology Observe / manipulate

First, think of a behavior or mental state. Levels of analysis in behavioral neuroscience. Most behaviors can usually be studied at multiple levels. Which is the right one? Common levels of analysis for human behavior (and mental states) include : Deep Superficial Nucleotides Genes Molecules Cells Circuits Neural systems Organs Organ systems Development Social environments Physical environments Evolutionary selection First, think of a behavior or mental state. Which level offers the best explanations for that behavior?

Contrasting popular levels of analysis in behavioral neuroscience Behavioral pharmacology studies bet on an intermediate level of analysis fMRI studies bet on a superficial level of analysis Whole genome association studies bet on a deep level of analysis

Where does ‘computational neuroscience’ fit in? Nucleotides Genes Molecules Cells Circuits Neural systems Organs Organ systems Development Social environments Physical environments Evolutionary selection “Molecular neuroscience” implies a molecular level of analysis of neuroscientific phenomena. “Cellular neuroscience” implies a cellular level of analysis of neuroscientific phenomena. Does “Computational Neuroscience” imply a particular level of analysis?

What’s missing in this level of analysis? Case study: Depression studied at a very superficial (social environment) level of analysis What’s missing in this level of analysis?

What’s missing in this level of analysis? Case study: Depression studied at a very deep (SNP) level of analysis What’s missing in this level of analysis?

Good hypotheses should make sense across different levels of analysis Behavioral neuroscientists tend to work at specifics levels of analysis. But if hypotheses at one level are correct, they should be consistent with facts at other levels. Computational models are used at different levels to support or test hypotheses Good hypotheses should make sense across different levels of analysis

Personal reflection on the “circuit” level… is it useful? Assumption: Adaptive behavior can be explained in part by the physical structure of neural circuits Challenges: neural circuits are hard to access for study neural circuit structure is hard to manipulate Nucleotides Genes Molecules Cells Circuits ? Neural systems Organs Organ systems Social environments Physical environments Evolutionary selection Rybak I A et al. J Physiol 2006;577:641-658

The new face of circuit level analysis in behavioral neuroscience: CONNECTOMES http://en.wikipedia.org/wiki/Connectome

Circuit level analyses- Successes… Monosynaptic stretch reflex Central pattern generators controlling motor rhythms (spinal, pyloric) Reversed OKR in Belladonna zebrafish mutant Autosomal Dominant Compelling Helioophthalmic Outburst Syndrome (ACHOO Syndrome) and limits… There are many ‘degrees of freedom’ of neural function, so structural can’t explain everything! Excitation / inhibition Neurochemical Modulation Gene regulation Plasticity Developmental effects Redundancy, etc etc These influence circuit function without changing circuit structure. Yet many neural circuit models don’t incorporate them. Bottom line: to understand how brains works, knowledge of neural circuit structure is necessary but usually not sufficient

Current Biology 2000, 10:595–598

THANK YOU! Take home messages My research examines the synaptic structure of topographical maps in hindbrain circuits. I teach courses in neuroscience, evolutionary psychology, psychopharmacology, and related Good neuroscience requires a multiple levels of analysis approach (consilience) The ‘right’ level to study depends on your goals, theory, and personal preference The neural circuit level of analysis is necessary but not sufficient for understanding how brains work Email me if you’re interested in talking more about this THANK YOU!