Cerebellum: Basic Circuitry Flashcards
After determining which parts of the brain are invovled and after establishing circuitry, what do we need to do?
Establish sites of plasticity- candidate sites from circuit details
Why do we want to know the cells where mossy fibre input (from the CS tone) and climbing fibre input (UCS shock or air puff) meet?
Synapses on these cells would be candidate sites for the plasticity underlying NMR conditioning
What is the cerebellum?
Little brain
Tight folds
Cerebellum has its own cortex
What are the two parts of the cerebellum?
Extensive cerebellar cortex
Compact deep nuclei
What does John Eccles 1967 work describe?
The structure of each of the cell types in the cerebellum
Their synaptic connections
Their electrophysiology
What is the 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 first input to purkinje cells?
Mossy fibre inputs
What are mossy fibre inputs?
In the case of NMR conditioning these fibres convey information about the tone (CS) to area HVI
Frequency of firing increases with tone intensity
What are granule cells?
Mossy fibres synapse with granule cells
The axons of granule cells form parallel fibres, that synapse with the dendrites of Purkinje cells
How many granule cells are there?
There are very many granule cells - ~80% of all neurons in the human brain
At least 100 per mossy fibre, hence “expansion recoding”
What are the three layers of the cerebellar cortex?
Molecular layer (top)
Purkinje layer (middle)
Granule layer (bottom)
What are purkinje cells?
Purkinje cells bodies lie in the middle (purkinje cell) layer
Largest cell in cerebellar cotex with distinctive dendritic field
Sole output cells of the cerebellar cortex- output comes out through axons of purkinje cells and these travel back down through the granular layer into the white matter
Each purkinje cell receives 150,000 parallel fibre synapses
What is in the molecular layer of the cerebellar cortex?
Parallel fibres and dendrites of purkinje cells
What is in the granule layer or the cerebellar cortex?
Small granular cells
What are golgi cells?
Get input from parallel fibres
Project back to the synapses between mossy fibres and granule cells
Are golgi cells inhibitory?
Yes
The more parallel fibre input they get the more they reduce it
What is the presumed function of golgi cells?
Control expansion recoding
What is expansion recoding?
Not quite known fully
Believed to be part of the machinery that ensures that information arising at the synapses is in a suitable form
What are two additional cell types in the molecular layer of the cerebellar cortex?
Stellate cells
Basket cells
Both get input from parallel fibres
Both inhibitory
What do basket cells synapse with?
Purkinje cell BODY
What do stellate cells synapse with?
Purkinje cell DENDRITES
What is the presumed function of stellate and basket cells?
To balance average excitatory drive from parallel fibres
What did Heiney et al. (2014) do?
Stimulated basket and stellate cells
What did Heiney er al. (2014) find?
Showed that you can silence the spontaneous firing of purkinje cells by stimulating basket and stellate cells
Showed that you can get control of movement kinematics
What are simple spikes?
The CS (mossy fibre) pathway causes purkinje cells to fire with simple spikes
These have spontaneous firing rates, usually about 50 spikes/sec but this can reach a maximum rate of >200 spikes/sec
What is the second input to purkinje cells?
Climbing fibre inputs
What are climbing fibre inputs?
Climbing fibre inputs come up from the inferior olive
Carry information about the UCS (airpuff/shock)
Typically fire at low frequencies (~1 spike/second)
Describe climbing fibres in relation to purkinje cells.
Climbing fibres are all wrapped around purkinje cell dendrites
-acts as one enormous synapse
Contrast mossy fibre input to climbing fibre input
Mossy fibres give rise to parallel fibres with about 150,000 different synapses per purkinje cell
Climbing fibres form one giant synapse
What are complex spikes?
Produced by climbing fibre input (UCS pathway)
Unusual in shape
Very reliable - whenever climbing fibres fire, purkinje cell also fires
What is the effect of complex spikes on output?
Little effect on output as they have a low frequency of firing compared to simple spikes
What is a candidate site for synaptic plasticity?
Cerebellar cortex
Because parallel fibres and climbing fibres both synapse on Purkinje cells of lobule HVI
What is the function of climbing fibre input?
Possibility that CF input acts to alter efficacy of parallel fibre synapses on Purkinje cells
Idea is that it acts as a teaching or error signal
How can we examine if climbing fibre input is a teaching signal that alters the synapses by LTD?
Stimulating parallel fibres paired with stimulating climbing fibres
-this explores whether the firing of PF and CF in conjunction can alter the efficacy of the PF synapses on PCs
Do we think that CF input (complex spikes) is a teaching signal?
Yes
If it is a teaching signal it fits with the fact that it is very relaible and does not affect the output
What is another candiate for synaptic plasticity?
Deep nuclei
Because mossy fibres (CS) and climbing fibres (UCS) also come together at the deep cerebellar nucleus (in the case of NM conditioning the relevant nucelus is the interpositus nucleus)
What is an issue with this second candidate?
Much less is known about the electrophysiology here, its not been extensively studied
What is a candidate site for synaptic plasticity?
Cerebellar cortex
Because parallel fibres and climbing fibres both synapse on Purkinje cells of lobule HVI
How could we relate a role in NMR condtioning to general functions of the cerebellum?
Clinical and experimental observations of cerebellar damage
Found the cerebellar damage does not cause paralysis but causes inaccurate movements that are slow and uncoordinated
What do clinical observations then suggest?
Other parts of the brain issue movement commands e.g. cerebral cortex
BUT
The role of the cerebellum is to ensure that they are carried out properly
What did Brindley (1964) suggest?
Purpose of the cerebellum is to learn motor skills, so when they have been learned a simple or incomplete message from the cerebrum will suffice to provoke their execution
-relates to user-friendliness- automaticity frees use the cerebral cortex
What is the general role of mossy fibre inputs?
Information about the current state of the body
Information about current motor commands
In NMR- converys infomation about the tone (CS) to area HVI
What is the general role of climbing fibre inputs?
Difficult to relate firing of CF to specific inputs
BUT
Usually related to sensory signals, such as touch, pain (e.g. airpuff, shock), visual inputs
What are cerebellar ‘modules’?
Individual areas of the cerebellar cortex
Structure of the cerebellar cortex is very uniform over its entire surface
Different regions have different inputs and outputs, but the same basic organisation
What are cerebellar ‘zones’?
External wiring is extremely diverse
Receive climbing fibre input from a unique region of the inferior olive and project to a unique region of the deep cerebellar nucleus
This in turn projects to a unique set of neural targets
What is the idea of a cerebellar ‘chip’?
Basic cortical microcircuit appears to be very similar for the entire cerebellum
But different regions have different external connections
Hence, the idea of a cerebellar ‘chip’ = same basic learning algorithm used for a wide range of tasks
Responsible for not just for learning motor skills, but for cognitive processing, and involved in e.g. dyslexia, autism
Why is the idea of a cerebellar ‘chip’ helpful?
Means we can borrow ideas from general theories of cerebellar function to understand NMR conditioning
And insights from NMR conditioning about basic cerebellar algorithm can be used to improve general theories
Overall, how is eyeblink conditioning related to other ‘cerebellar’ tasks?
They are all mediated by the same basic neural circuit
