Ch. 8 Synaptic Plasticity

Model Organism

Sea Slug Aplysia californica

Why is Aplysia a good model

Has 10,000 neurons (not many)

Large Neurons (1mm)

Stereotypical behaviors that are well characterized

Gill Withdrawal Reflex

Stimulation to gill will lead to its withdrawal

Habituation

Organism gets used to repeated stimulus

Reduced response to something that initially caused a strong response

Habituataion in Aplysia

When gill initially touched, there is a huge response (contraction)

Over time and repeated touches, organism learns nothing happens and reaction decreases

Sensitization

Increased response due to paring stimulus with shock

Sensitization in Aplysia

Caused heighten response even when there was no shock

What does habituation and Sensitization mean

Organism is learning

Synaptic plasticity underlies behavioral plasticity

Mechanisms Underlying Behavioral Sensitization

Gill withdrawal reflex involves sensory and motor neurons and interneurons

Sensory Neuron → Modulatory interneuron → Interneuron → Motor neurons

Neuronal Depression

Equivalent to habituation

Stimulation of siphon elicits reduced response in the gill motor neuron over time

Neuronal Facilitation

Equivalent to behavioral sensitization

Activation of serotonin modulator interneuron enhances gill motor neuron response to sensory neuron stimulation

Mechanisms for Synaptic Plasticity

Short term Sensitization

Long Term Sensitization

Short Term Sensitization Mechanism

Faciliatory Interneuron releases serotonin

Activate serotonin metabotropic receptors (G protein)

Activate cAMP

Activation of protein kinase A

What does PKA do in short term sensitization

Phosphorylates K channels reducing probability of opening and keeping the cell depolarized

Extends action potential and increase probability of opening Ca channels which increase intracellular concentration of Ca and increase neurotransmitter release

Long Term Sensitization

Stimulus is continuous and long

Effects can last for weeks on cell

Increases gene expression and protein synthesis

How does long term sensitization effect gene expression

Same mechanism of short term sensitization however, because cell is active for longer, there are transcription changes in the cell

Synthesis of Ubiquitin causes PKA to stay active, causes more phosphorylation and activity

Ubiquitin Hydrolase

Degrades PKA regulatory subunit in long term sensitization

This cause catalytic subunit of PKA to be free for longer periods of time

Hippocampus

Formation and retrieval of memory, episodic as well as spatial memory

Place cells

Processes in Hippocampus

Long term potentiation and long term depression

Long term Potentiation

Synaptic Strength

Strengthening of synapses because they are important for behavior

Changes brain by adding more spines to dendrites

Long Term Depression

Decrease in synaptic strength

Connections are not as important of behavior

Low frequency stimulation

Tetanus

High frequency stimulation, sustained reaction

Induces Long term potentiation

Increases response of the pathway and stays sustained

When does Tetanus Effect Cell most

When it activates pathways that work together

Only works if pathway one is stimulated then pathway two

Strengthens the reaction of both pathways

Can postsynaptic depolarization induce long term potentiation

Yes

Strong depolarization pulses to postsynaptic neuron paired with test stimulations of presynaptic neuron also induces LTP

Mechanism of LTP

AMPA and NMDA

Ionotropic glutamate receptors

Metabotropic glutamate receptors

What is special about NMDA

It has a Mg block

Only a strong stimulus can activate NMDA because of this block, this can only be done with tetanus

What happens during LTP

Ca entry via NMDA receptors activate CaMKII and protein kinase C

Ca and phosphorylation leads to insertion of AMPA receptors

Increased Sensitivity to Glutamate

Mechanism of Long Term Depression

Ca entry via NMDA receptor activates phosphatases

The rise of Ca is slower and smaller than LTP

Dephosphorylation causes internalization of AMPA receptors and leads to less sensitivity to glutamates

Long Term Depression in the Cerebellum

Different than hippocampus

Involves parallel fibers (AMPA and mGluR) and climbing fibers (voltage gated Ca channels)

Increase calcium causes activation of PKC and internalization of AMPA

Spike Timing Dependent Plasticity

Plasicity caused by precise synchrony between activity of presynaptic and post synaptic neuron

Must be within a few miliseconds

Either can occur depending on which fires first

Presynaptic Cell Fires First

Long term potentiation

Postsynaptic Cell Fires First

Long term depression