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Laboratory of Tom FischerDepartment of Psychology
Neural networks and behavior
• How neural circuits work
• How changes in neural circuits contributes to learning
Synaptic plasticity
• Plasticity “rules”: what causes synapses to change?
• Cellular mechanisms of synaptic change
Lab interests
Levels of analysis
BEHAVIOR
SYSTEMS
NETWORKS
NEURONS
SYNAPSES
MOLECULES
GENES
Goal of lab: Direct integration of cellular and
behavioral levels of analysis
How do changes in genes, synapses etc. contribute to changes in
behavior?
Aplysia californica
Why study Aplysia?
Invertebrate systems have fewer and larger neurons & simpler types of behavior
• More tractable
• Fewer technical obstacles
“Simple system” approach to learning
• Examine individual neurons relevant to behavior
First cellular studies in 1965
• Ladislav Tauc and Eric Kandel
Kandel: 2000 Nobel Prize in medicine
• “...for discoveries concerning signal transduction in the nervous system”
History of memory research using Aplysia
Siphon Withdrawal Response (SWR)
What can Aplysia learn?
Non-associative learning
• Sensitization (tail shock)
• Habituation (repeated siphon stimulation)
Associative learning
• Classical (Pavlovian) conditioning
• Context conditioning
• Operant conditioning
Aplysia californica
Siphon withdrawal network
Studying learning in intact animals
Behavioral studies
The “reduced preparation”
Cellular Studies
Computer modelingThe whole is the sum of its parts
Developmental analysis
How do neural networks develop, and how does behavior change as they do?
Levels of analysis
Where does one start?
• Choice depends on goals of experimenter
• Many careers focus on only one (or a few) levels
• Some studies skip levels: behavioral genetics
BEHAVIOR
SYSTEMS
NETWORKS
NEURONS
SYNAPSES
MOLECULES
GENES
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“Bottom-up” approach
1. Start at level of neurons
• Construct a ‘wiring diagram” by determining the functional properties of the neurons
2. Predict behavioral functions based on cellular observations
Not always an easy approach
• Can you understand how a TV set works by understanding each individual component?
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“Top - down” approach
1. Start with an analysis of the animal's behavior
• Behavior is what one ultimately wants to explain
• Determine the types of stimuli that elicit or change the behavior
2. Progressively trace neural circuit from body to brain
• Match cellular properties to behavioral observations
Simplified SWR circuit
The “low-threshold” circuit
• Responds to touch, water movement
Defining the circuitBottom-up approach
How do you identify motor
neurons?How do you
identify sensory neurons?
Circuit CrackingWho is connected to who?
How does one determine synaptic
connectivity?
High-divalent technique
Increase concentration of divalent ions in recording solution:
• Increase Mg++ and Ca++ by about 3X
Raises threshold of neurons so that they are less likely to be activated by a single input
Circuit CrackingWho is connected to who?
How does one determine sign of
synapse?
Synaptic plasticity
Synapses change with “experience”
• Activity of cell
• Release of neuromodulators
Learning and memory
• Long-term changes in synapses
How do you know the changes you observe really matter for behavior?
Neuromodulation
Serotonin is released into nervous system by tail shock
Activity-dependent plasticity
Modulation of activity-dependent plasticity
Metaplasticity: the plasticity of plasticity
What changes with learning?
Excitatory synapses are enhanced
Inhibitory synapses are reduced
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Relating neurons to behavior
1. Correlation
• Correlation does not imply causation!
2. Sufficiency
• Is direct activation of neuron sufficient to cause/change behavior?
3. Necessity
• Is the activity of a neuron necessary for behavior/change?
Model
Following tactile stimulation, behavioral threshold is increased
• Duration of behavioral response decreases
Tactile stimulation: brush tail (5 sec)
• Behavioral regulation lasts for approx. one minute
Hypothesis:
• Regulation due to activity-dependent enhancement of L30
L30 model
Enhanced inhibition onto excitatory neurons
Experimental questions
1. Are L30s activated and enhanced by tail brush?
• What test is this?
2. Does direct activation of L30 produce the same effects as tail brush?
3. Does preventing L30 activity during tail brush eliminate behavioral regulation?
Brush tail
Measure SWR by “tapping” siphon
Record from neurons
• MNs: activity reflects behavior
The reduced prep
Cellular correlate of behavior
Activity in neurons reflects behavioral change
L30 correlates
Tail stimulation activates and enhances L30 synapses
• Time course of enhancement matches time course of behavioral regulation
L30 sufficiency
L30 necessity
Tail-shock regulation
If tail shock modulates L30 plasticity, does it likewise modify tail-brush regulation?
What did we learn about L30?
Studying L30 informed us about the role of inhibition in neural networks
L30s regulates behavior following tactile events
• Why? Signal to noise? Freezing response?
Learning-related stimuli regulate inhibition
• Changes way animal responds to simple stimuli
• Increases likelihood of further change? May allow excitatory cells to become more active (LTP?)