Memory & Learning (LTP + LTD + Drosophila Mushroom Bodies))

Question 1

What is procedural memory?

Answer 1

Skills you can do unconsciously, such as riding a bike

Question 2

What is declarative memory?

Answer 2

Memory available to the conscious mind, can be encoded in symbols or language

Question 3

What is explicit memory?

Answer 3

Memory you can actively recall such as riding a new bike.

Question 4

What is implicit memory?

Answer 4

Memory cannot be consciously recalled such as learning to ride a bike. Implicit memory is either procedural memory, classical conditioning or priming (exposure to stimulus altering a response).

Question 5

What are some simple systems for studying neural circuits and their advantages?

Answer 5

Simple systems include snails, worms, insects, cockroaches etc.
+ Neuronal size is small, there are only 302 neurons in Aplysia (Sea hares)
+ Circuits are not too complex, easy to understand
+Mapping tools make it easier to genetically edit a single neuron

Question 6

Tell me about habituation in Aplysia

Answer 6

The gill-withdrawal reflex occurs when the gills are touched/hit with a water jet. Repeated stimuli can reduce the gill-withdrawal reflex e.g., 15-20 touches with 10-20 second intervals between them.
In Aplysia, there is a sensory neuron on the gill which synapses to a motor neuron that controls gill withdrawal.

Question 7

Where does habituation occur in Aplysia?

Answer 7

Habituation occurs at the synapse between the sensory neuron and the motor neuron. As the stimuli is maintained, the readily-available transmitter vesicles are depleted resulting in a decrease in the rate of nt release.

Question 8

Tell me about sensitisation in Aplysia.

Answer 8

The gill-withdrawal reflex can be increased when there is an unconditioned stimulus (US) paired with a conditioned stimulus (CS), e.g., when a shock (US) is paired with weak touch (CS) on the gill the gill withdrawal reflex can last for days. This is a demonstration of associative learning.

Question 9

Where does sensitisation occur in Aplysia?

Answer 9

The L29 neuron axon terminal synapses onto the sensory neuron just before the synapse to the motor neuron.
1. L29 releases serotonin into the sensory neuron
2. Serotonin binds to GPCR activating a g-protein
3. g-protein activates adenylyl cyclase; cAMP production
4. cAMP activates PKA which closes K+ ion channels
5. It takes longer to repolarise the presynaptic terminal leading to maintained NT release.

Question 10

What is a hebbian synapse?

Answer 10

It is a type of synapse involved in memory and learning. When two neurons are activated at the same time, the connection between them is strengthened. They were discovered by Donald Hebb.

Question 11

What is the simplified hippocampal circuitry?

Answer 11

Entorhinal to dentate to CA3 to CA1 to either the fornix or subiculum

Question 12

Where does LTP usually occur?

Answer 12

Occurs at the CA3 to CA1 synapse when there’s either High Frequency Stimulus (HFS) or coincidence of inputs will lead to potentiation. It is
Shows neuron input specificity - only stimulated neurons can undergo LTP

Question 13

Tell me about glutamate receptors involved in learning

Answer 13

a) NMDA receptors increase Ca2+ on the post-synaptic side
b) Non-NMDA receptors such as AMPAR and KAR depolarise the cell upon glutamate binding, these are key in the transmission of information across synapses (EPSPs)
c) mGlut receptors (mGluR) are metabotropic

Question 14

Describe early phase LTP

Answer 14

Before early phase LTP can occur, a separate depolarising input must remove a voltage-dependent Mg2+ block. This pre-activates the NMDAR, this allows glutamate to activate NMDARs alongside AMPARs
1. Pre-synaptic neuron fires fully and glutamate is released which can now open due to being pre-activated
2. This leads to calcium influx into the post-synaptic neuron activating Calmodulin Kinase II (CaMKII)
3. CaMKII undergoes a conformational change and becomes catalytic
4. CaMKII phosphorylates protein leading to increased AMPAR current
5. This stimulates AMPA-fication, the delivery of premade AMPA receptors to the post-synaptic neuron. Future responses to impulses result in stronger and longer EPSPs

Question 15

Describe Late phase LTP

Answer 15

Late phase LTP requires protein synthesis this can take upto an hour after initiation.
1. cAMP activates PKA, PKA activated subunits diffuse into the nucleus and phosphorylate CREB
2. CREB recruits CREB Binding Proteins (CBP)
3. CREB-CBP is a transcriptional activator, it leads to an increase in expression in of proteins involved at the synapse.
CREB-1 is replaces CREB-2 during late phase LTP
It is still unclear how synthesized proteins translocate from the ER to the correct synaptic terminal.

Question 16

What is the simplified Cerebellum LTD circuitry?

Answer 16

Both the negative mossy fibres and climbing fibres synapse to purkinje fibres. Mossy fibres synapse to parallel fibres before synapsing to purkinje fibres.

Question 17

Where and when does LTD occur?

Answer 17

LTD occurs in the parallel fibre to purkinje fibre synapse. An LTD will occur when there is coincidence of climbing fibres and parallel fibre inputs to the purkinje fibre.
The Albus Marr model suggests that CF inputs indicate a motor error and weaken the PF:PF synapse.

Question 18

Describe cerebellar LTD mechanism

Answer 18

1. mGluR activation activates Gαq
2. Gαq activates PLC which activates PKC
3. PKC phosphorylates the AMPAR GluR2 subunit triggering AMPAR internalisation via endocytosis
4. Subsequent parallel fibre depolarisation results in reduced purkinje fibre EPSP

Endocytosis inhibitors can prevent LTD.

Question 19

Tell me about hippocampal LTD and BCM theory

Answer 19

Bienestock-Cooper-Munro theory suggests that the synapses which are active when the rest of the cell isn’t become weaker.
- LTD occurs at the CA3-CA1 synapses with low frequency stimulation (LFS - 1-5Hz)
- LTD can reverse LTP: depotentiation
- LTD is also Ca2+ dependent
- The degree of NMDAR activation dictates the probability of inducing LTD versus LTP

Question 20

What is classical conditioning?

Answer 20

One example is Pavlov’s dog.
A conditioned stimulus (ringing of a bell) has to precede or coincide with the unconditioned stimulus (delivery of food). Upon the CS being paired with the US, the CS alone could stimulate the response to the US, e.g., ringing a bell stimulated the salivatory reflex of the dog.
Automated analyses of Drosophila movement in response to odours makes observing conditioning very easy.

Question 21

Tell me about GAL4/UAS system and the Split-GAL4 system

Answer 21

GAL4/UAS system allows the expression of arbitrary transgenes in a population of cells. The expression of the transgene is inducible via galactose presence.
Split-GAL4 system allows for a higher level of specificity of cells affected. The GAL4 DBD and AD are placed under different promoters. When both promoters are active, GAL4 is reconstituted and the transgene expressed.

Question 22

Tell me about Kenyon cells in the Drosophila Mushroom Body

Answer 22

Kenyon cells receive inputs from the Antenna lobe Glomeruli projection neurons. They require multiple simultaneous in order to fire, ensuring that KC firing is highly selective.
Kenyon cells are able to sample a small region of the PN coding space converting a dense combinatorial code into a sparse selective code.

Question 23

Tell me about DANs and MBONs in the Drosophila Mushroom Body

Answer 23

KC axons are innervated by MBONs and DANs which are predominantly inhibitory neurons.
MBON and DAN compartments line up in the Mushroom Body.
DANs (Dopaminergic neurons) encode reward/punishment memory.
MBONs (Mushroom Body Output Neurons) encode approach/avoidance behaviours.
DANs are paired with MBONs of the opposite valence due to their inhibitory natures.
E.G., if there is a punishment associated with an odour, the DAN encoding the punishment releases dopamine to the MBON encoding the approach behaviour. Dopamine released by the punishment DAN is an inhibitory transmitter preventing an EPSP in the approach MBON.