Cerebellum Basic Circuitry

Question 1

Now we know that the cerebellum is involved with NMR conditioning, what is the next step?

Answer 1

Locate the sites of synaptic plasticity that mediate simple delay conditioning of the nictitating membrane response

Question 2

How do the CS and the US arrive at the cerebellum?

Answer 2

The tone (CS) arrives at the cerebellum through the mossy fibre input

The shock or airpuff (US) arrives at the same region of the cerebellum through the climbing fibre input

Question 3

Where would the candidate sites for plasticity be?

Answer 3

At which cells do these two inputs (mossy fibres and climbing fibres) meet? Synapses on these cells would be candidates for plasticity for NMR conditioning

Question 4

What are the two candidate sites of plasticity?

Answer 4

1. Cerebellar cortex - parallel fibres and climbing fibres both synapse on Purkinje cells of lobule HVI
2. Deep cerebellar nuclei: mossy fibres and climbing fibres both synapse on neurons in the anterior interpositus nucleus

Question 5

What are the two parts of the cerebellum?

Answer 5

Extensive cerebellar cortex
Compact deep nuclei

Question 6

Describe the basic cerebellar cortical circuitry

Answer 6

Mossy fibres excite granule cells

Granule cell axons (parallel and ascending fibres) excite Purkinje cells

Purkinje cells inhibit cells in cerebellar nuclei

Question 7

What is the role of the mossy fibres in NMR conditioning?

Answer 7

They convey information about the tone CS to area HVI

Frequency of firing increases with tone intensity

Question 8

What is the role of the granule cells in NMR conditioning?

Answer 8

Mossy fibres synapse with granule cells

The axons of granule cells form parallel fibres, that synapse with the dendrites of Purkinje cells

There are many granule cells in the brain - at least 100 per mossy fibre (expansion recoding)

Question 9

What is expansion recoding?

Answer 9

Neural activity space is increased through a random projection of mossy fibre inputs onto a significantly larger population of granule cells

Expansion recoding is thought to play a key role in pattern separation prior to associative learning

Pattern separation is a process in which neural circuits transform similar input activity patterns into more distinct output patterns

Question 10

What is the role of the Purkinje cells?

Answer 10

Sole output cells of the cerebellar cortex

Question 11

What are the characteristics of Purkinje cells?

Answer 11

Each Purkinje cell receives approx 150,000 parallel fibre synapses
Largest cells in the cerebellar cortex
Distinctive dendritic field - flattened out like a fan

Question 12

Describe the gross anatomy of the cerebellum

Answer 12

3 layers

1. Molecular = parallel fibres and Purkinje cell dendrites
2. Purkinje layer = Purkinje cells
3. Granular = Golgi cells, granule cells, mossy fibres

Question 13

What other cell types are found in the cerebellum?

Answer 13

Golgi cells
Stellate cells
Basket cells

Question 14

What are the characteristics of Golgi cells?

Answer 14

Receive input from parallel fibres
Project back to synapses between mossy fibres and granule cells
Are inhibitory - so the more parallel fibre input they get, the more they reduce it

Question 15

What is the presumed function of Golgi cells?

Answer 15

To control expansion recoding

Question 16

What are the characteristics of stellate and basket cells?

Answer 16

Both found in the molecular layer
Both receive input from parallel fibres
Basket cells synapse with Purkinje cell BODY
Stellate cells synapse with Purkinje cell DENDRITES

Question 17

What is the presumed function of stellate and basket cells?

Answer 17

They are inhibitory interneurons which control the activity of Purkinje cells by balancing the average excitatory drive from parallel fibres

Question 18

What did Heiney et al. (2014) study?

Answer 18

Stimulation of basket and stellate cells
Can silence the spontaneous firing of Purkinje cells

Abstract:
We used an optogenetic approach in awake mice to show for the first time that transiently suppressing spontaneous activity in a population of PCs is sufficient to cause discrete movements that can be systematically modulated in size, speed, and timing depending on how much and how long PC firing is suppressed. We further demonstrate that this fine control of movement kinematics is mediated by a graded disinhibition of target neurons in the deep cerebellar nuclei

Question 19

What sort of spiking does the conditioned stimulus cause in Purkinje cells?

Answer 19

Simple spikes

Question 20

What are the characteristics of simple spikes?

Answer 20

Occur spontaneously and are driven by parallel fibre input

Spontaneous firing rates usually about 50 spikes/sec

Maximum rate >200 spikes/sec

Question 21

What is the second input to the Purkinje cells?

Answer 21

Climbing fibres

Question 22

What are the characteristics and function of the climbing fibres?

Answer 22

Cell bodies found in the inferior olive
Carry information about the unconditioned stimulus - airpuff or shock
Typically fire at low frequencies (1 spike/sec)
Climbing fibres wrapped round PC dendrites - acts as one enormous synapse
Contrast with mossy fibre input - gives rise to parallel fibres

Question 23

How are complex spikes created?

Answer 23

Produced by climbing fibre input

Question 24

What are the characteristics of complex spikes?

Answer 24

Very reliable - whenever climbing fibre fires, PC also fires
Low frequency of firing compared with simple spikes, so little effect on output

Question 25

What is the function of the climbing fibre input?

Answer 25

Possibility that CF input acts to alter efficacy of parallel fibre synapses on Purkinje cells = LONG TERM DEPRESSION
Fits with reliability and lack of effect on output

Question 26

Where else does the mossy fibre and climbing fibre input and what does this mean?

Answer 26

Mossy fibre (CS) and climbing fibre (US) information also come together at the interpositus nucleus (deep nuclei)

Therefore, second candidate site for synaptic plasticity

Question 27

How can a role in NMR conditioning be related to general function of the cerebellum?

Answer 27

Clinical and experimental observations of cerebellar damage

–> Does not cause paralysis, but makes many movements inaccurate, slow and uncoordinated

Question 28

What is the influential suggestion of the function of the cerebellum?

Answer 28

Appears that other parts of the brain issue movement commands - the role of the cerebellum is to ensure they are carried out properly

Question 29

What did Brindley (1964) suggest?

Answer 29

Suggested in an abstract that the purpose of the cerebellum is to learn motor skills, so that when they have been learned, a simple or incomplete message from the cerebrum will suffice to provoke their execution

Question 30

What is the role of the mossy fibres?

Answer 30

In the case of NMR conditioning, these convey information about the tone CS to area HVI

For other areas of the cerebellar cortex
- Current state of body
- Current motor commands

Question 31

What is the role of climbing fibres input in general?

Answer 31

Often difficult to relate the firing of climbing fibres to specific inputs
Usually related to sensory signals, such as touch, pain, visual inputs
Suggested to be some sort of error signal to guide learning

Question 32

What are cerebellar modules?

Answer 32

Each module consists of a longitudinal strip or zone of Purkinje cells within the cerebellar cortex and is defined by its climbing input originating from a circumscribed subdivision of the inferior olivary complex

Structure of cerebellar cortex is very uniform over its entire surface

Different regions have different inputs and outputs but same basic organisation

Question 33

What are cerebellar zones?

Answer 33

External wiring is extremely diverse
Purkinje cells in a given parasagittal strip of cortex receive climbing fibre input from a unique region of the inferior olive
Purkinje cells in a given parasagittal strip of cortex project to a unique region of the deep cerebellar nuclei
This in turns projects to a unique set of neural targets

Question 34

Explain the idea of the cerebellar chip

Answer 34

Mossy fibre input –> Cerebellar microzone (central area) –> Purkinje cell output

Climbing fibre teaching signal into the cerebellar microzone (error signal)

Question 35

What is the reason behind the cerebellar chip?

Answer 35

Basic cortical microcircuit appears to be very similar for the entire cerebellum, but different regions of cerebellar cortex have very different external connections - hence the idea of the cerebellar chip - same basic algorithm used for a wide range of tasks

Question 36

What is the cerebellar chip responsible for?

Answer 36

Not just for learning motor skills but for cognitive processing and involved in dyslexia, autism etc

Question 37

How is the cerebellar chip useful for our understanding of NMR conditioning?

Answer 37

The basic algorithm is also the one used in the much simpler NMR conditioning
To understand NMR conditioning we can borrow ideas from general theories of cerebellar function
Insights from NMR conditioning about basic cerebellar algorithm can be used to improve general theories