Laboratory of Tom FischerDepartment of Psychology

Thomas.Fischer@Wayne.edu

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?)