NMR Conditioning: Basic Circuitry

Question 1

Once you’ve picked a task to assess what happens in the brain when we learn something what two things do we do?

Answer 1

1. determine which parts of the brain are involved- where we look for synaptic changes that underpin the learning
2. Establish circuitry

Question 2

Why do we need to establish circuitry?

Answer 2

To establish where the sites of plasticity are

Question 3

What are the three basic techniques for establishing neural circuitry?

Answer 3

1. Neuroanatomy
2. Electrophysiology
3. Manipulation

Question 4

In terms of neuroanatomy, what do we want to find out?

Answer 4

What connects with what

Question 5

For collections of neurons what two things do we what to know about them?

Answer 5

Where do they project?

Which regions project to them?

Question 6

What is an issue with looking at neuronal projections in neuroanatomy?

Answer 6

Usually cannot see them directly, even with a microscope because there is a mass of cells and fibres

Question 7

How can we establish neuronal circuitry by neuroanatomy?

Answer 7

By using “tract-tracing” methods

Question 8

What is retrograde transport?

Answer 8

Inject Substance X into a nucleus around a set of cell bodies

The substance you choose will be one that then gets transported back up from the synapse, up the axon and into the cell body

This is the opposite direction from the way the cell usually functions so its retrograde/backwards transport

Question 9

What is anterograde transport?

Answer 9

Inject Substance X into the cell and it shows you where the cells axons end in synapses, it is transported to terminals

This is known as forward/anterograde transport

Question 10

What can you use retrograde/anterograde transport for?

Answer 10

To create demonstrations of connectivity in the brain

Question 11

What does electrophysiology tell us about basic circuitry?

Answer 11

What signals are carried by neural connections

Electrophysiology can establish neuronal properties e.g. by recording from neurons while a sensory stimuli is presented
e.g. the orientation specificity of neurons in the visual cortex

Question 12

What does manipulation tell us about circuitry?

Answer 12

What happens when a particular region is removed, inactivated temporarily or stimulated

Try to predict effects from anatomy anf physiology

Standard systems neuroscience

Question 13

The circuitry is broken down into 5 parts, what are they?

Answer 13

1. Unconditioned reflex pathway
2. Output of anterior interpositus nucleus controls the conditioned response
3. Output of HVI (eyeblink region of cerebellar cortex) controls the anterior interpositus nucleus
4. HVI (eyeblink region) receives information about conditioned stimulus via mossy fibres
5. HVI (eyeblink region) receives information about unconditioned stimulus via climbing fibres

Question 14

The unconditioned reflex circuit is a basic three neuron arc reflex, what are the three neurons?

Answer 14

Sensory neuron (in gasserian ganglion)
Interneuron (in trigeminal nucleus)
Motoneuron (in abducens nucleus)

Question 15

Describe the unconditioned reflex circuit.

Answer 15

Input is from the cornea or the skin around the eye (periorbital UCS)
It travels in the trigeminal nerve and it’s cell bodies are located in the gasserian ganglion
This projects to the spinal trigeminal nucleus oral subdivision (synapse 1)
Then projects to the accessory abducens nerve (synapse 2) and travels out in the abducens nerve to the retractor bulbi muscle that pulls the eye back in the orbit

Question 16

What are the implications of the unconditioned reflex circuit only being a 3 neuron reflex arc?

Answer 16

Means there are only three synapses
This makes it very fast
Overall takes 20milliseconds, where 16milliseconds is mechanical (muscle movement)

Quick to protect the eye- makes sense

Question 17

What does the retractor bulbi muscle do in the unconditioned reflex circuit?

Answer 17

Pulls the eye back into the orbit
The the nictitating membrane slides passively over the eyeball

Question 18

What shows us that the output of the anterior interpositus nucleus controls the CR?

Answer 18

If you damage the relevant area then you remove the CR with little effect on the UCS

If we lesion the deep cerebellar nuclei we block conditioning and any pre-existing conditioning is abolished and cannot be re-learned

Lesions confined to the anterior interpositius nucleus are effective so they must control the CR

Question 19

What did Steinmetz et al. (1992) find?

Answer 19

A properly placed lesion blocks retention of previously learnt conditioning, and prevents any new learning

Question 20

How does the CR command signal get from the anterior interpositus nucleus to the accessory abducens nucleus (which controls the retractor bulbi muscle)?

Answer 20

Doesn’t project direct to accessory abducens, but via a midbrain structure, the (contralateral) red nucleus

Question 21

What does the red nucleus do?

Answer 21

Its a motor coordination nucleus

Red nucleus transports the CR command to the accessory abduencns nucleus which controls the retractor bulbi muscle, so it’s suggested that the red nucleus is relevant to coordinating eye closure

Question 22

How can we confirm the red nucleus is involved in transporting the CR command signal?

Answer 22

Through it’s inactivation by muscimol

If we block the red nucleus by the Gabba antagonist muscimol, it blocks performance of the CR

Question 23

What is the conditioned reflex pathway: cerebellar cortex?

Answer 23

All output from the cerebellar cortex goes through the deep cerebellar nuclei
-so main input to interpositus nucleus is from cerebellar cortex
Different regions of cortex project to different parts of deep cerebellar nuclei
The particular region that projects to anterior interpositus and is concerned with eye-blink is in the hemisphere of lobule VI (HVI)
Lobule HVI inhibits the interpositius nucleus which then releases activity in the red nucleus and then in the accessory abducens nucleus
So it inhibits, and the accessory abducens nucleus activates the retractor bulbi muscle and that produces the response

Question 24

What is the evidence for the role of the cerebellar cortex in the conditioned response pathway?

Answer 24

Lessions here cause selective loss of the CR (Yeo, 1987)

Question 25

Why is lesion work as evidence not straightforward?

Answer 25

Because cortical lesions probably abolish the CR if large enough (and bilateral)

Question 26

What is more clear cut than lesion work?

Answer 26

Stimulation data

Question 27

How does cerebellar cortex ‘stimulation’ tell us how the cerebellar cortex is invovled?
-Disinhibition

Answer 27

Output from cerebellar cortex inhibits deep cerebellar nuclei

The output cells are called purkinje cells which are inhibitory- stopping them firing causes the cells in the deep cerebellar nuclei to fire more (form of disinhibition)

Cortical output (purkinje cells) are tonically active in resting state (100 spikes/s), so to get an eyeblink we need to silence cortical output comepletely, hence the term disinhibition
The cortical output is inhibited because it is inhibitory itself so it disinhibits the cells in the deep cerebellar nuclei

Question 28

What did Heiney et al (2014) find in the ‘stimulation’ of the cerebellar cortex?

Answer 28

Found a way of silencing cerebellar neurons and inhibiting purkinje cells

Examined the eyelid- as you increase the duration of your inhibition you get longer responses and as you increase stim intensity you get bigger responses and if you alter the rise time you alter the rise time of the response

Question 29

Why was Heiney et al.’s (2014) study important?

Answer 29

Nice demonstration that the parameters of the stimulation you’re applying are related to eye position & velocity = good evidence this is the mechanism that we’re looking at

Question 30

What can we use to see where the HVI region of the cerebellum get its input from?

Answer 30

Anatomical studies
-show this region gets its input from the pons

Question 31

Decribe the condtioned reflex pathway: conditioned stimulus.

Answer 31

Pons is located at the bottom of the brain
Receives information about light & sound from various structures in the forebrain, including cerebral cortex and the midbrain
Projects to the cerebellum via mossy fibres

Question 32

Why do we think the pons carries information about the CS?

Answer 32

Lesions of the pontine nuceli abolish conditioning and prevent conditioning

Can use electrical stimulation of pontine nuclei as a CS (instead of tone) and get good learning and an eyeblink response

Question 33

What is the conditioned reflex circuit: UCS pathway?

Answer 33

The cerebellum also receives information about the unconditioned stimulus (shock around the cornea)

The UCS reflex arises at the cerebellar cortex from the trigemnial nucelus via relay in the inferior olive, the axons of the inferioir olive neurons are called climbing fibres which have unusual propertes that project to the cerebellum
This is a pathway that send the error signal to the system

Question 34

What is the evidence climbing fibres carry information about the unconditioned stimulus?

Answer 34

Lesions in relevant region of inferior olive abolish conditioning and prevent relearning

Can use electrical stimulation of climbing fibres as a US, and get conditioning