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Lecture 5&6 Havekes

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Learning objectives - Reproduce the role of hippocampus in specific learning tasks - Reproduce the differences between Pavlovian Conditioning and Operant Conditioning - Reproduce the role of the hippocampus and amygdala in tone-cued fear and contextual fear conditioning - Reproduce how the role of protein synthesis in the consolidation of contextual fear conditioning was studied - Reproduce the difference between the fear conditioning and active shock avoidance - Reproduce how the object location task works and why it requires the hippocampus - Reproduce how the rotarod task works and the brain regions it requires - Reproduce why protein synthesis for the formation of long-term memories and how the role of protein synthesis in memory can be studied - Reproduce the meaning of the term synaptic plasticity and why the estrus cycle is an elegant example of what is meant by synaptic plasticity - Reproduce what LTP is and what the differences are between E-LTP and L-LTP - Reproduce how E-LTP and L-LTP compare to short-term and long-term memory - Reproduce the pre- and postsynaptic glutamatergic signaling events that occur during LTP induction - Reproduce the differences between E-LTP en L-LTP at the molecular level - Reproduce how LTP can lead to spine growth and how this relates to protein synthesis - Reproduce the impact of sleep deprivation on hippocampal spine numbers, hippocampus-dependent memory formation and L-LTP - Reproduce the impact of cofilin inhibition in the sleep-deprived brain on hippocampal spine numbers, L-LTP in the hippocampus, and hippocampus-dependent memory formation

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Lecture 10 – Havekes 5,6
Chapter 24


Hippocampus-dependent learning tasks
- Spatial water maze
- Contextual fear conditioning
- Object-location memory task

Hippocampus-independent learning tasks
- Non-spatial water maze
- Tone-cued fear conditioning
- Active shock avoidance (=operant learning)
- Rotarod task

Classic conditioning
Pavlovian conditioning: association between a neutral stimulus (CS) and a positive or negative
stimulus (US).
Operant conditioning: association between a neutral stimulus (CS) and a positive or negative
stimulus (US). In addition to Pavlovian conditioning, it is associating a voluntary behaviour with a
consequence (e.g. tapping a bell or hand for food, or jumping to the other side for avoiding a shock).

Fear conditioning stimulates “freezing behavior”




Tone cued fear is hippocampus independent, and amygdala dependent
Contextual fear is hippocampus dependent and amygdala dependent as well.

Fear conditioning is also Pavlovian conditioning because it can do nothing to avoid the shock by doing
voluntarily behaviour, in contrast, active shock avoidance is operant conditioning.

Object-location memory and rotarod task
The object location memory task requires the hippocampus and the rotarod task requires the motor
cortex and cerebellum.

, How is a memory stored in the brain?
Anisomycin is a protein synthesis inhibitor. It blocks the development of new proteins, it blocks the
translational parts in neurons. Blocking this synthesis negatively influences fear conditioning.

For the storage of information the spines and axon terminals, the connection needs to be
strengthened, this is the basis of memory. For strengthening this connection and making it bigger,
new proteins are needed for building blocks.

So:
- Protein synthesis is required for making new axonal-dendritic connections
- Protein synthesis is required for strengthening existing connection
- Synaptic plasticity is the process of making new connections and/or changing the strength of
existing connections (the estrus cycle is an example)
- Long term potentiation is a form of synaptic plasticity and the molecular basis of memory
storage.

Studying long-term potentiation (LTP) in hippocampal slices
- These kinds of studies allows researchers to study individual pathways and signaling
mechanisms using antagonists and agonists.
- Multiple slices and thus studies from a single hippocampus
- Also great temporal resolution in terms of drug treatment

E-LTP and L-LTP




Early LTP is a weak form of learning that is not persistent (short-term memory that is not
consolidated into long-term memory). EPSP is a measure of relative strength of the neuronal
connections before and after a stimulation.
Late LTP is a strong form of learning that is persistent (short-term memory that is successfully
consolidated into long-term memory).

Blocking protein synthesis does not only prevent long term memory formation and L-LTP, it also
prevents the growth of dendritic spines, following LTP-induction.
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