27 Nov 2020
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In the 1980s, Thompson and associates discovered
that eyeblink conditioning in rabbits depends on the
Week 4 - Brain & Clinical Lecture Notes
Jan. 30 2020
Classical Conditioning: Brain Substrates
• How does classical conditioning work at the neural
level?
•
cerebellum.
Mammalian Conditioning of Motor Reflexes
• CS (tone/light) input pathway:
– Sensory input is processed in various
brain regions and is sent to sensory
areas of the pontine nuclei
– Pontine output - mossy fibers - send info
to:
1. Granule cells in cerebellar cortex
2. Interpositus nucleus within the
cerebellum
• US (air puff) input pathway:
– Received by inferior olive of midbrain,
output via climbing fibers to:
1. Interpositus nucleus
2. Purkinje neurons in the cerebellar cortex
Mammalian Conditioning of Motor Reflexes
▪ Both the Purkinje cells & the interpositus can detect & store the CS & US association
▪ CR output:
– Interpositus output can
• activate the CR (blink to tone)
• inhibit initial stage of US pathway
– Purkinje cells inhibit output of the interpositus nucleus
Note: Interpositus does not generate URs (e.g., blink to airpuff)

Electrophysiological Recording in the Cerebellum
▪ The interpositus can generate the CR.
▪ What does the inhibition of the interpositus by Purkinje cells accomplish?
o Purkinje cells actively inhibit the interpositus most of the time.
▪ In well-trained animals, Purkinje cell firing rate declines with the CS
▪ Shutting off the Purkinje inhibition of the interpositus enables the CS to generate CRs.
Brain Stimulation Substitutes Training
Fig. 4.20: Four days of training using
stimulation of the inferior olive as the US
(blue line) produces the same amount of
conditioned eyeblink response as 4 days of
training with an air puff US (orange line).
▪ Can mimic both the CS (tone/light) and US (air puff) with electrical stimuli to brain
o CS - stimulate portion of pontine nuclei that normally respond to the specific
tone
o US - stimulate the inferior olive to create a blink
▪ This direct brain stimulation can produce CRs!
▪ Even more amazingly, real CSs (e.g., tone) can then activate CRs as well! (Writing a
memory to the brain!)
Roles of the Interpositus & Cerebellum
▪ The CR’s output pathway is the interpositus nucleus
o Even small interpositus lesions destroy and prevent CRs.
▪ Lesions in cerebellar cortex (including Purkinje cells) affect timing the CR correctly
with respect to the CS.
Rescorla-Wagner + Eyeblink Conditioning
▪ Rescorla-Wagner: errors of prediction drive learning.