Dean NMR 2

Question 1

What does nictitating mean in Latin?

Answer 1

Winking

Question 2

What steps do we need to take to find out what happens in the brain when we learn something?

Answer 2

1. Pick a task you think is soluble (NMR conditioning)
2. Determine which parts of the brain are involved
3. Establish the circuitry

Question 3

What happens when you cut off the forebrain from the brainstem?

Answer 3

Separates the cerebral cortex, forebrain and hippocampus from the brainstem and cerebellum (a decerebrate animal) but delayed conditioning is still possible
Such conditioning is not possible after cerebellar damage

Question 4

What questions do we have about the cerebellum?

Answer 4

How does it connect with CS and US inputs and also with the CR output?

Question 5

What is the first basic technique used to establish the circuitry?

Answer 5

Neuroanatomy
Establishes what connects with what, where do neurons project, which regions project to them
Usually can’t see this directly even with a microscope so have to use ‘tract-tracing’ methods

Question 6

Outline retrograde transport

Answer 6

Inject substance X around the cell body
This transports back to the cell body of afferent neuron
After suitable time can section the brain to view the transport

Question 7

What is needed from substance X?

Answer 7

Needs to be suitable for transportation

Need to be able to see it and where its gone

Question 8

Outline anterograde transport

Answer 8

Inject substance X
Travels forward to the terminals
Can view the transport in sections of the brain

Question 9

What is the second technique for establishing circuitry?

Answer 9

Electrophysiology
What signals are carried by these connections?
Record an individual neuron while the animal is presented with sensory stimuli and/or performing motor responses
Example: orientation specificity of neurons in the visual cortex of rabbits

Question 10

What is the third technique for establishing circuitry?

Answer 10

Manipulation
What happens when a particular region is removed, inactivated or stimulated?
Try to predict effects from anatomy and physiology

Question 11

What are the 5 stages of circuitry?

Answer 11

1. Unconditioned Reflex Pathway
2. Conditioned Reflex Circuit: Conditioned Response
3. Conditioned Reflex Pathway: Cerebellar Cortex
4. Conditioned Reflex Circuit: CS Pathway
5. Conditioned Reflex Circuit: US Pathway

Question 12

Outline the unconditioned reflex pathway

Answer 12

The peri-orbital shock is registered by sensory neurons with cell bodies outside the brain in the Gasserian Ganglion
These travel via the trigeminal nerve V onto the spinal trigeminal nucleus (oral subdivision)
These neurons then project to motor nucleus - accessory abducens nucleus.
The axons leave this nucleus and travel to the muscle that pulls the eye back (retractor bulbi nucleus) via the Abducens Nerve VI

Question 13

What is a special feature about the unconditioned reflex pathway?

Answer 13

It is extremely fast (about 20ms)
It is an example of the basic 3 neuron reflex arc:
1. sensory neurons (in the Gasserian ganglion)
2. interneuron (in the trigeminal nucleus)
3. motor neuron (in the abducens nucleus)
There are only 3 synapses (2 in the CNS, 1 nerve-muscle synapse)

Question 14

What does the retractor bulbi muscle do?

Answer 14

Pulls the eye back into the orbit and the nictitating membrane then slides over the eyeball

Question 15

Outline the Conditioned Response in the Conditioned Reflex Circuit e.g. how does the CR command signal get from the AI nucleus to the accessory abducens nucleus?

Answer 15

Doesn’t project directly to the accessory abducens but via the contralateral red nucleus in the mid brain (which is a relatively big detour)
Inactivation of the red nucleus by muscimol (a GABA agonist) blocks performance of the conditioned response
- still unclear what it does at present but may help to coordinate the general facial flinch

Question 16

Outline the role of the cerebellar cortex in the conditioned reflex pathway

Answer 16

The main input to the interpositus nucleus is from the cerebellar cortex.
The particular region that projects to the anterior portion of the IPN and concerned with eye blink is the hemisphere of lobule VI (HVI)
This inhibits the IPN
By stimulating this region the output inhibits the deep cerebellar nuclei
But this cortical output is tonically active so to get an eye blink need to silence the cortical output (e.g. disinhibition) which releases the IPN

Question 17

What did Heiney et al. (2014) achieve?

Answer 17

Inhibited the Purkinje cell activity in mice using optogenetics, which therefore released the IPN and caused an eye blink
So we can selectively control eye blinking using the silencing of Purkinje cells

Question 18

What is optogenetics?

Answer 18

Shining a very small light on a small specific part of the brain which in turn selectively activates that area

Question 19

Outline the CS pathway in the conditioned reflex circuit

Answer 19

Anatomy demonstrates that the HVI gets input from the pons
Stimuli enter the pontine nuclei which project to the cerebellar cortex via mossy fibres
If you lesion the pontine nuclei you abolish conditioning and can use electrical stimulation of pontine nuclei as a CS to get good learning

Question 20

Outline the US pathway in the conditioned reflex circuit

Answer 20

The cerebellum also receives info about the US
The neurons in the spinal trigeminal nucleus (an interneuron) bifurcate and send another axon to the inferior olive (which is located at base of brain right below the cerebellum)
This projects to the cerebellar cortex via climbing fibres
Lesions in the relevant region of the inferior olive abolishes conditioning and prevents relearning
Can use electrical stimulation of climbing fibres as a US to get conditioning