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Parallels between cerebellum- and amygdala-dependent conditioning

Key Points

  • Some of the clearest evidence on the localization of memory within the mammalian brain has come from studies of associative learning, especially through the use of classical or Pavlovian conditioning, in which animals learn to express a conditioned response to a predictive or conditioned stimulus (CS) paired with an unconditioned stimulus (US). This review focuses on two of the most widely used forms of Pavlovian learning: eyelid and fear conditioning.

  • In eyelid conditioning, the deep cerebellar nuclei and overlying cerebellar cortex seem to mediate the acquisition and storage of discrete motor memories. By contrast, evidence from fear conditioning points to the lateral nucleus of the amygdala (LA) as a key component of the brain system that is responsible for the formation of aversive emotional memories.

  • Despite being mediated by different brain systems, these forms of learning might use a similar sequence of events to form new memories. Recent data point to a 'trigger-and-storage' model, in which the initial encoding and subsequent long-term storage of memory are mediated by separate groups of neurons.

  • Two sets of cerebellar neurons, the Purkinje cells and neurons in the anterior interpositus nucleus, change their activity during eyelid conditioning and so represent potential sites of plasticity. Recent evidence indicates that the cerebellar cortex might participate in the initiation of learning, whereas the deep cerebellar nuclei are more involved in the long-term storage of memory.

  • The dorsal region of the LA (LAd) is a site of CS–US convergence. Two distinct sets of neurons in the LAd could contribute differentially to the initiation and storage of fear-conditioning memories. Cells in the dorsal tip of the LAd develop conditioning-induced enhancement of their auditory responses very early in training, but cells in more ventral regions take longer to reach maximal response levels.

  • Several important questions remain unanswered, including whether there is complete transfer of memory from the 'soft' trigger cells to the 'hard' storage cells. It is also not known whether plasticity in the trigger cells is required for the induction of plasticity in the storage cells, or if the induction of soft and hard plasticity can proceed independently, but at different rates.

Abstract

Recent evidence from cerebellum-dependent motor learning and amygdala-dependent fear conditioning indicates that, despite being mediated by different brain systems, these forms of learning might use a similar sequence of events to form new memories. In each case, learning seems to induce changes in two different groups of neurons. Changes in the first class of cells are induced very rapidly during the initial stages of learning, whereas changes in the second class of cells develop more slowly and are resistant to extinction. So, anatomically distinct cell populations might contribute differentially to the initial encoding and the long-term storage of memory in these two systems.

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Figure 1: Neural circuits engaged during eyelid conditioning.
Figure 2: Neural circuits engaged during fear conditioning.
Figure 3: The trigger-and-storage model.

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Correspondence to Javier F. Medina.

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FURTHER INFORMATION

learning and memory

 MIT Encyclopedia of Cognitive Sciences

conditioning

conditioning and the brain

learning

magnetic resonance imaging

memory

single-neuron recording

Glossary

EXTINCTION

The reduction and cessation of a predictive relationship and behaviour after the omission of a reinforcer (negative prediction error).

GOLGI CELLS

Cerebellar interneurons located in the granule cell layer. Their axonal terminals form part of the cerebellar glomeruli.

PURKINJE CELLS

Inhibitory interneurons in the cerebellum that use GABA as their neurotransmitter. Their cell bodies are situated beneath the molecular layer, and their dendrites branch extensively in this layer. Their axons project into the underlying white matter, and they provide the only output from the cerebellar cortex.

INFERIOR OLIVARY NUCLEUS

A nucleus situated in a bulge on the ventral medullary surface of the brainstem. Its neurons form very strong excitatory synapses with those of the cerebellum.

PARABRACHIAL AREA

A nucleus situated in the pons that transmits information from the viscera to the hypothalamus and amygdala.

STRIA TERMINALIS

One of the main efferent projections of the amygdala. It innervates regions that include the nucleus accumbens and the hypothalamus.

MITOGEN-ACTIVATED PROTEIN KINASE

Any member of a family of protein kinases that are important for relaying signals from the cell membrane to the nucleus.

PROTEIN KINASE A

Also known as cyclic-AMP-dependent protein kinase. One of a class of enzymes that use ATP as a phosphoryl-group donor to phosphorylate hydroxyl or phenolic groups on their target proteins.

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Medina, J., Christopher Repa, J., Mauk, M. et al. Parallels between cerebellum- and amygdala-dependent conditioning. Nat Rev Neurosci 3, 122–131 (2002). https://doi.org/10.1038/nrn728

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