Cerebellum Basic Circuitry Flashcards
Now we know that the cerebellum is involved with NMR conditioning, what is the next step?
Locate the sites of synaptic plasticity that mediate simple delay conditioning of the nictitating membrane response
How do the CS and the US arrive at the cerebellum?
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
Where would the candidate sites for plasticity be?
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
What are the two candidate sites of plasticity?
- Cerebellar cortex - parallel fibres and climbing fibres both synapse on Purkinje cells of lobule HVI
- Deep cerebellar nuclei: mossy fibres and climbing fibres both synapse on neurons in the anterior interpositus nucleus
What are the two parts of the cerebellum?
Extensive cerebellar cortex
Compact deep nuclei
Describe the basic cerebellar cortical circuitry
Mossy fibres excite granule cells
Granule cell axons (parallel and ascending fibres) excite Purkinje cells
Purkinje cells inhibit cells in cerebellar nuclei
What is the role of the mossy fibres in NMR conditioning?
They convey information about the tone CS to area HVI
Frequency of firing increases with tone intensity
What is the role of the granule cells in NMR conditioning?
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)
What is expansion recoding?
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
What is the role of the Purkinje cells?
Sole output cells of the cerebellar cortex
What are the characteristics of Purkinje cells?
Each Purkinje cell receives approx 150,000 parallel fibre synapses
Largest cells in the cerebellar cortex
Distinctive dendritic field - flattened out like a fan
Describe the gross anatomy of the cerebellum
3 layers
- Molecular = parallel fibres and Purkinje cell dendrites
- Purkinje layer = Purkinje cells
- Granular = Golgi cells, granule cells, mossy fibres
What other cell types are found in the cerebellum?
Golgi cells
Stellate cells
Basket cells
What are the characteristics of Golgi cells?
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
What is the presumed function of Golgi cells?
To control expansion recoding
What are the characteristics of stellate and basket cells?
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
What is the presumed function of stellate and basket cells?
They are inhibitory interneurons which control the activity of Purkinje cells by balancing the average excitatory drive from parallel fibres
What did Heiney et al. (2014) study?
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
What sort of spiking does the conditioned stimulus cause in Purkinje cells?
Simple spikes
What are the characteristics of simple spikes?
Occur spontaneously and are driven by parallel fibre input
Spontaneous firing rates usually about 50 spikes/sec
Maximum rate >200 spikes/sec
What is the second input to the Purkinje cells?
Climbing fibres
What are the characteristics and function of the climbing fibres?
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
How are complex spikes created?
Produced by climbing fibre input
What are the characteristics of complex spikes?
Very reliable - whenever climbing fibre fires, PC also fires
Low frequency of firing compared with simple spikes, so little effect on output
What is the function of the climbing fibre input?
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
Where else does the mossy fibre and climbing fibre input and what does this mean?
Mossy fibre (CS) and climbing fibre (US) information also come together at the interpositus nucleus (deep nuclei)
Therefore, second candidate site for synaptic plasticity
How can a role in NMR conditioning be related to general function of the cerebellum?
Clinical and experimental observations of cerebellar damage
–> Does not cause paralysis, but makes many movements inaccurate, slow and uncoordinated
What is the influential suggestion of the function of the cerebellum?
Appears that other parts of the brain issue movement commands - the role of the cerebellum is to ensure they are carried out properly
What did Brindley (1964) suggest?
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
What is the role of the mossy fibres?
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
What is the role of climbing fibres input in general?
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
What are cerebellar modules?
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
What are cerebellar zones?
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
Explain the idea of the cerebellar chip
Mossy fibre input –> Cerebellar microzone (central area) –> Purkinje cell output
Climbing fibre teaching signal into the cerebellar microzone (error signal)
What is the reason behind the cerebellar chip?
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
What is the cerebellar chip responsible for?
Not just for learning motor skills but for cognitive processing and involved in dyslexia, autism etc
How is the cerebellar chip useful for our understanding of NMR conditioning?
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
