Learning in Aplysia Flashcards
Learning definition
relatively permanent change in behaviour as a result of experience
Memory definition
when current behaviour is under control of past experience
Non-associative learning
animals learn about properties of stimulus they encounter
Associative learning
Classical (pavlovian) learn about relationship of one stimulus to another. Instrumental learn about the relationship between a stimulus and an action
Early proposal for memory?
Reverberating circuits. But results like those of Squire, Slater and Chase 75 showed that ECT did not disrupt memory in the long term
Hebb
Postulate for learning. Summarised as cells that fire together wire together
Habituation (Non associative)
decrease in response to increasingly repeated non-noxious stimuli
Dishabituation (non-associative)
increase in response to a stimulus following its intense presentation
Sensitisation (non-associative)
enhanced response to a range of stimuli following an intense or noxious stimulus
Sherrington
studied habituation of flexion in animals. Suggested habituation was result of a decrease in function of synapses to motor neurons
Spencer and Thompson
Habituation in spinal reflexes of cat. Showed changes at synapse were responsible
Kandel
Extensive work on the aplysia earning him the nobel prize
Aplysia Californica
20,000 neurons but 200 consistent and major ones. Consistent wiring in all Aplysia
Withdrawal reflex
US touch mantle or siphon, UR gill withdrawal
Mechanism of habituation
Repeated tactile stimulation and UR decreases. Castellucci et al 1970 (fewer action potentials from gill withdrawal motor neurons with each touch). Castelluci and Kandel 1974 (However sensitivity to artificial neurotransmitter does not decrease and the sensory neurons are still firing a signal). Therefore sensory neurons must be releasing less transmitter
Why do sensory neurons release less transmitter?
Klein, Shapiro and Kandel 1980 - less calcium enters presynaptic terminal reducing exocytosis. Gingrich & Byrne, 1985 - depletion of neurotransmitter in sensory neuron
Mechanisms of sensitisation
Facilitatory interneurons driven by tail sensory neurons synapse on the axon terminals of siphon sensory neurons. Release of neurotransmitters at axon terminals of siphon sensory neurons modifies their response to siphon stimulation. Presynaptic facilitation
Role of interneurons and serotonin
Serotonin mimics sensitisation. Interneurons increase cAMP –> increases depolarisation of presynaptic neuron, allows more calcium into the terminal which increases exocytosis and alters the way calcium participates in mobilizing transmitter vesicles
Plasticity
Habituation and sensitisation are the result of a plastic change in the function of neurons but changes can also be long term. Evidence for structural changes of neurons at the synapses for long term effects
Pavlovian conditioning
allows animals to learn the relationship between one stimulus and another. Allows us to deal with unobservable mental phenomena (ideas) by studying them through observable behavioural processes
Associative learning in Aplysia
CS - light siphon touch, US - tail shock, UR - gill withdrawal and CR strong gill withdrawal
Rescorla 1968
Rats presented with a tone and unconditioned stimulus. Only when the CS and US were contingently presented did they produce a CR. Therefore the CS-US paired are associative learners and CS-US unpaired are sensitisation group
Differential conditioning
these experiments on the Aplysia prove that it is not sensitisation but conditioning. CS1 and CS2 paired seperately with one US. When tested with CS2 on a CS1 group the response (CR) is lower than the CS2 test would be
In paired CS-US training the effect of the US on active CS-UR sensory synapses is much stronger (conditioning). Why?
timing crucial to processes promoting enhancement. in addition to effects of cAMP (see sensitization), a G-protein, adenylate cyclase is increased. one form of this protein binds to calcium (which is in greater abundance) and promotes more production of cAMP. similar processes detected in Drosophila and Hermissenda - mammalian systems seem to differ
Mechanism of classical conditioning
US - tail shock excites interneuron. CS - Mantle sensory neuron and interneuron simultaneously active – large change in subsequent sensory neuron transmitter release
Memory in Aplysia
Mostly presynaptic effects. No evidence of memory cells or reverberating circuits
Bliss and Lomo 1970
long term potentiation. studied slices of hippocampus in vitro. Stimulated axons in the perforant path and measured activity in the dentate gyrus.
Properties of LTP
Long term and only occurs when firing of presynaptic neuron is followed by firing of postsynaptic neuron. In Bliss and Lomo experiments a tetanic stimulation bought about a higher EPSP even after a week or month
NMDA receptor
LTP most widely studied at these sites. Acts as a coincidence detector only firing when pre and post neurons are. Mg ion displaced when post synaptic neuron is patially depolarised. Allows glutamate to bind and so channel opens allowing calcium ions through. These ions initiate changes in the cell.
Evidence for post synaptic changes in LTP
Muller, Joly and Lynch (1988) - showed that the change in synaptic efficacy was mediated by changes in AMPA receptors. AFTER induction of LTP potentiation effect was abolished by blocking AMPA but not NMDA receptors
Tocco et al. (1992) measured the number of AMPA and NMDA receptors using radio-labelled ligands and found that LTP changed AMPA, but not NMDA, receptor numbers
Blocking protein synthesis prevents LTP (Nguyen, Abel & Kandel, 1994)
What will more AMPA receptors do?
More dendritic spines are being produced
More AMPA receptors are sitting on these spines, more space for them as well
Signal is therefore more likely to be detected
Presynaptic changes in LTP
Calcium entering post synaptic cell activates secondary messengers (kinases) and NO is released. Acts as retrograde transporter effecting pre-synaptic cells. Possible by acting on soluble guanyl cyclase–>cyclic GMP–>more glutamate release
Glanzman, 1995
Classical conditioning of Aplysia’s withdrawal reflex mediated by
Activity-dependent presynaptic facilitation (ADPF): at synapses between central sensory and motor neurons.
Postsynaptic mechanism: Hebbian potentiation of the sensorimotor synapses
Plasticity at sites other than central monosynaptic sensorimotor connections, including peripheral sites
Walters and Byrne
differential conditioning results from different presynaptic effects
Carew, Pinsker & Kandel, 1972
Habituation lasts 2 or 3 hours following a single 10-stimulus habitation session, but several such sessions can produce habituation that lasts for weeks
Emptage & Carew, 1991
As a result of presynaptic facilitation – sensory fibres from the Aplysia tail synapse on facilitatory serotonergic inter-neurons, which in turn synaps on the buttons of siphon sensory neurons
Byrne & Kandel, 1996
Applications of serotonin to Aplysia sensorimotor synapses produces sensitisation lasting minutes to days
Cleary, Lee & Byrne, 1998
Long term sensitisation: multiple mechanisms, including lasting increases in motor neuron excitability
Carew, Walters & Kandel, 1981
Increase in intensity of the reflex is much greater that if the two stimuli are presented in an unpaired fashion. proves associative nature of effect CC in aplysia
Carew, Hawkins & Kandel, 1983
Performed the discriminated classical conditioning tasks
Bailey & Chen (1983, 1988)
electron microscopy: long-term habituation & sensitisation leads to structural changes in synaptic terminals of siphon sensory neurons. Sensory neurons:
Fewer active zones of NT release
Smaller active zones of NT release
More synaptic vesicles
Pinel
Changes in postsynaptic neurons can be rapid through ion-channel linked receptors or slow and enduring though NT binding G-protein linked receptors and 2d messengers produced as a result
Secondary messengers (Pinel)
second messenger increased in buttons of siphon-sensory neurons in response to the serotonin released by tail-shock-activated inter-neurons.
o Activates protein kinase A which closes many potassium channels in buttons which increases duration of each action potential which increases influx of calcium & release of NT in response to each touch of siphon.
Byrne & Kandel (1996): this mechanism largely accounts for short-term synaptic facilitation; long-term depends on a second cascade of changes mediated by protein kinase C.
Kelso, Ganong & Brown, 1986
LTP Develops only if the firing of the presynaptic neuron is followed by firing of postsynaptic neuron
Evidence for LTP in learning and memory (Pinel)
- LTP can be elicited by low levels of stimulation (mimic normal neural activity)
- Effects are most prominent in structures that have been implicated in l&m (e.g. hippocampus).
- Behavioural changes can produce LTP-like changes in Hippocampus (Iriki et al., 1989)
- Drugs that influence l&m have parallel effects on LTP (Brown et al., 1988; Skelton et al., 1987)
- Induction of maximal LTP blocks learning of a Morris water maze until LTP has subsided (Castro et al., 1989)
- Mutant mice that displat little hippocampal LTP have difficulty learning the Morris water maze (Silva et al., 1992)
Calcium in LTP
- Calcium probably exerts its effects by activating protein kinases in the neural cytoplasm (Grant & Silva, 1994; Linden & Routtenberg, 1989).
