7. Background and Basic Circuitry

Question 1

NMR conditioning and the cerebellum

Answer 1

• CS (tone) arrives at cerebellum as mossy fibre input
• US (shock of air puff) arrives at same region of cerebellum as climbing fibre input
• where do these inputs meet? - synapses for these cells could be sites for plasticity

Question 2

cerebellar cortex and deep nuclei

Answer 2

cerebellum has its own cortex with cell bodies on top of underlying white matter
two parts of the cerebellum:
1. extensive cerebellar cortex
2. compact deep nuclei

Question 3

cerebellar cortical circuitry (candidate 1)

Answer 3

• mossy fibres excite granule cells
• granule cell axons (parallel and ascending fibres) excite Purkinje cells
• Purkinje cells inhibit cells in deep nuclei

Question 4

Purkinje cells

Answer 4

• sole output of the cerebellar cortex
• cell bodies in the middle of cortex (Purkinje cell layer)
• each Purkinje cell recieves around 150’000 parrallel fibre synapses
• largest cells in the cerebellar cortex with a large dendritic tree (like a fan)

Question 5

Mossy Fibre

Answer 5

• input for CS
• NMR conditioning - convey information about the CS (tone) to area HVI
• probably: the frequency of firing increases with CS intensity

Question 6

Granule Cells

Answer 6

• Mossy fibres synapse with granule cells
• axons of granule cells form parallel fibres that synapse with the dendrites of Purkinje cells
• 80% of all cells in the brain are granule
• 100 granule cells per mossy fibre = expansion recoding

Question 7

expansion recoding

Answer 7

something to recode temporally bearing inputs into more spatially diverse outputs

Question 8

layers of cerebellar cortex

Answer 8

• more simple to cortex (which has 6)
• molecular layer
• Purkinje cell layer
• Granule cell layer
• white matter underneath

Question 9

Golgi cell

Answer 9

• input from parallel fibres
• project back to synapses between mossy fibres and granule cells (granule cell layer)
• are inhibitory - more parallel fibre input the more it is inhibited
• thought to regulate information flow (expansion recoding)

Question 10

stellate and basket cells

Answer 10

• both inhibitory and get input from parallel fibres
• Heiney et al., (2014) - supported this by silencing Purkinje cells through their activation
• found in molecular layer
• synapse with Purkinje cell body (basket)
• synapse with Purkinje cell dendrites (stellate)
• thought to balance average excitatory drive from parralel fibres

Question 11

simple spikes

Answer 11

Purkinje cells fire spontaneously (e.g. simple spikes)

• usually about 50 spikes/s
• parallel fibre input can increase this to > 200 spikes/s

Question 12

climbing fibres

Answer 12

• input for the US
• second input to Purkinje cells comes from climbing fibres
• have cell bodies in the inferior olive
• carry information about the US (air puff)
• typically fire spontaneously at low frequencies = 1 spike/s

Question 13

climbing fibres and purkinje cells

Answer 13

all wrapped around Purkinje cell dendrites

• acts as an enormous synapse
• give rise to parallel fibres
• 150’000 synapses for Purkinje cell

Question 14

effects on Purkinje cell firing

Answer 14

• very unusual shape of spikes produced by climbing fibre input
• whenever the climbing fibre fires the Purkinje cell does too (complex spikes)
• low frequency of firing compared to simple spikes

Question 15

long term depression

Answer 15

• what is the function of climbing fibre input?
• possibility that climbing fibre input acts to alter the efficacy of parallel fibre synapses on Purkinje cells
• activate the parallel fibre (on top of cerebellum) and you see a response in Purkinje cell
• you can pair this stimulation (say 100 times) with the stimulation of climbing fibres
• when you stimulate the climbing fibres on their own, their activation is depressed (LTD)
• fits in with the idea that climbing fibres convey an error signal
• not driving output but are telling the system its done something wrong by weakening the synapses

Question 16

deep nuclei (candidate 2)

Answer 16

• mossy fibres (conditioned stimulus carrier) and climbing fibres (unconditioned stimulus carrier) information comes together in the interpositus nucleus (deep nuclei)
• second candidate site for plasticity

Question 17

summary of plasticity sites

Answer 17

cerebellar cortex = parallel fibres and climbing fibres both synapse on Purkinje cells of lobule HVI

deep cerebellar nuclei = mossy and climbing fibres both synapse onto neurons in the interpositus nucleus

Question 18

how can a role in NM conditioning be related to general functions of the cerebellum?

Answer 18

thought that the role of the cerebellum is to ensure other brain regions are carrying out movements properly (automaticity - frees up rest of cerebral cortex)

Question 19

mossy fibre inputs - general

Answer 19

in NMR conditioning, these convey messages to lobule HVI about the conditioned stimulus
- for other areas of cerebellar cortex > current state of body (e.g. location of arms and legs) and current motor commands (e.g. what system is trying to do)

Question 20

climbing fibre general

Answer 20

hard to relate the firing of climbing fibres to specific inputs

• usually related to sensory signals (touch/pain/vision)
• thought to be some sort of error signal to guide learning

Question 21

cerebellar ‘modules’

Answer 21

• individual areas of cerebral cortex
• structure is very uniform across its whole surface (but connections very different)
• different regions have different inputs and outputs but same basic organisation

Question 22

cerebellar zones

Answer 22

external wiring is very diverse

• Purkinje cells in a given parasagittal strip of cortex projecting to a unique set of targets
• recieve climbing fibre input from unique region in inferior olive
• lead to the idea of the cerebellum being made of lots of chips (like microchip)

Question 23

cerebellar chip idea

Answer 23

same basic principle as a micro chip

• same piece of circuitry that can be plugges into different parts of the brain responsible for a range of things (motor skills, regulation of emotion, social behaviour, memory)
• could also be involved in a range of disorders
• responsible for much more simple NMR conditioning
• if we want to understand NMR conditioning we can borrow ideas from cerebellar circuitry

Question 24

how is eye blink conditioning related to other tasks?

Answer 24

all mediated by the same circuitry