3.4 Habituation and Sensitization

habituation

response to a stimulus weakens after repeated exposures

• implicit

• short or long term

short term habituation example

• after repeated exposure to loud sound which initially startled it, the rat stops responding to sound

long term habituation

ignoring the sound of trains after living there for a few days or weeks

Sensitization

• response to a stimulus strengthens after a noxious stimulus is co-applied

  • presentation of strong stimulus enhances response to other stimuli

example of sensitization

a loud cargo train goes by your house, startling you, and for the rest of the day, you find that you are startled by the normal passenger trains rolling by

how is sensitization different from classical conditioning

• classical conditioning creates a NEW behavioral response to a neutral stimulus while…

• sensitization strengthens an ESTABLISHED behavioral response

Aplysia (marine snail)

• model used to study simple forms of memory

• exhibits gill withdrawal reflex

Gill withdrawal reflex

• when siphon touched/shocked

  • gill retracts in response

pathway for gill withdrawal reflex

siphon → sensory neuron → gill → motor neuron

How might we test the hypothesis that habituation is due to reduced excitation of sensory neurons

• keep stimulating/activating the mechanosensors on the sensory nerve

• BUT BLOCK ACTION POTENTIALS IN THE NERVE

• nerve blocked 10th-18th stimuli

  • weak to no response

• nerve unblocked

  • strong response

    • DOES NOT INDUCE HABITUATION

      • if that’s where habituation is happening, then you’d still expect a weak response on the 20th stimulus.

      • sensory neuron refreshed and ready to signal

Short-term habituation in Aplysia

Repeated stimulation of the gill results in less and less contraction of the gill (weaker gill withdrawal reflex), i.e., it exhibits a weaker behavioral response to same stimulus

Reduced synaptic transmission at neuromuscular junction?… Muscle fatigue? How to test this hypothesis?

• Directly stimulate the motor neuron

• No. The NMJ and muscle do not habituate.

Could gill withdrawal reflex be due to reduced synaptic transmission from sensory neurons to motor neurons?

• directly stimulate sensory neuron

• Yes!

  • We artificially stimulate sensory neuron and the effect on motor neuron is weaker and weaker

How does decreased transmitter release from sensory neuron induce habituation

• presynaptic action potentials in sensory neuron is unchanged

• EPSPs motor neuron decreases

  • thus reduced gill behavior

Long-term habituation in the gill-withdrawal reflex

• loss of sensory-motor synapses in circuit

  • fewer sensory neurons synapsing onto motor neurons

• 4 sessions of 10 stimuli

  • separated by several hours to 1 day

    • long term habituation

short term learning vs. long term learning

• short term learning involves changes in the strength of existing synapses

• long term learning involves structural changes

  • adding or removing synapses

sensitization in aplysia

• After shocking its tail, gill withdrawal is much more severe compared to the same stimulus before the shock

short term vs long term sensitization (graph)

What part of pathway is affected by sensitization

• increased transmitter release from sensory neuron

Cellular mechanism pathway for short-term sensitization

• tail shock

• activates serotonin modulatory neuron

  • into release of serotonin (5-HT)

• sensory neuron detects 5-HT

• increased cAMP

• increased PKA

  • increased phosphorylation K+ channels

    • closes these channels

• prolonged action potentials

  • more Ca++ entry into axon terminal

• more glutamate release

  • excitatory

Cellular mechanism for long-term sensitization

• everything from short term + PKA

  • translocated to nucleus

  • transcriptional changes

    • synaptic growth

• PKA also results information of dendritic spines

  • that connect to motor neuron

long term habituation and long term sensitization structural changes

• habituation: less dendritic spines

• sensitization: more dendritic spines

• number of synapses per sensory neuron increases or decreases

When long-term synaptic facilitation occur at one synapse (due to it being strongly stimulated),

other neurons that are also stimulated (EVEN WEAKLY) will also experience long term synaptic facilitation

1 pulse of serotonin onto synapse with motor neuron A

short term facilitation of synapse with motor neuron A

5 pulses of serotonin onto synapse with motor neuron A

produces long-term facilitation of synapse with motor neuron A

5 pulses of serotonin onto synapse with motor neuron A + 1 pulse onto cell B synapse

• produces long-term facilitation of both synapses!

  • EPSP amplitude on Y axis

How do new proteins get localized to co-active synapses

• new proteins that stimulate synapse growth

  • which are produced at synapse being strongly stimulated

• specifically go to active synapses (INCLUDING WEAK ONES)

  • to grow more synaptic contacts with motor neuron