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Operation and plasticity of hippocampal CA3 circuits: implications for memory encoding

Nature Reviews Neuroscience volume 18, pages 208–220 (2017)Cite this article

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Key Points

  • On theoretical grounds, the architecture of CA3 circuits seems to be well adapted for the rapid storage and retrieval of associative memories. This is thought to require plastic changes in the strength of specific synaptic contacts.

  • Dentate gyrus cells provide sparse but powerful synaptic mossy fibre connections to CA3 pyramidal cells, which display a large dynamic range of presynaptic plasticity. This repertoire was recently extended to include postsynaptic plasticity of NMDA receptor-mediated excitatory postsynaptic currents (EPSCs), making these synapses competent for conventional long-term potentiation of AMPA receptor-mediated EPSCs.

  • Local recurrent connectivity gives rise to the CA3 autoassociative network amenable to spike-timing dependent plasticity, which can be facilitated by heterosynaptic interactions.

  • Local GABAergic loops control spike transfer at CA3 connections. GABAergic connectivity is subject to prominent structural and molecular plasticity in relation to memory encoding.

  • Mice impaired in the plasticity of CA3–CA3 or dentate gyrus–CA3 connections show deficits in one-trial memory tasks. Nevertheless, a direct link between memory and functional plasticity of specific excitatory or inhibitory connections is still awaited.

Abstract

The CA3 region of the hippocampus is important for rapid encoding of memory. Computational theories have proposed specific roles in hippocampal function and memory for the sparse inputs from the dentate gyrus to CA3 and for the extended local recurrent connectivity that gives rise to the CA3 autoassociative network. Recently, we have gained considerable new insight into the operation and plasticity of CA3 circuits, including the identification of novel forms of synaptic plasticity and their underlying mechanisms, and structural plasticity in the GABAergic control of CA3 circuits. In addition, experimental links between synaptic plasticity of CA3 circuits and memory are starting to emerge.

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Figure 1: CA3 circuits and their proposed role in memory.
Figure 2: Presynaptic and postsynaptic plasticity at mossy fibre–CA3 pyramidal cell synapses.
Figure 3: Synaptic integration and heterosynaptic plasticity in CA3 pyramidal cells.
Figure 4: GABAergic control of CA3 pyramidal cells.

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Acknowledgements

The authors are grateful to A. Treves and E. Einarsson for initial discussions on the manuscript. The work was supported by the Centre National de la Recherche Scientifique and by the Agence Nationale de la Recherche (grant Hippencode).

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  1. University of Bordeaux, Interdisciplinary Institute for Neuroscience, Centre National de la Recherche Scientifique (CNRS), F-33000, Bordeaux, France

    Nelson Rebola, Mario Carta & Christophe Mulle

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  1. Nelson Rebola
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PowerPoint slides

Glossary

Neural ensembles

Populations of neurons that are involved in particular and/or specific neural computations.

Associative memories

Memories that enable an individual to learn and remember the relationship between unrelated items.

Attractor network

A neural network that has one or more stable 'states' (that is, patterns of firing across neurons). The stable states are determined by the strengths of the recurrent connections between the neurons in the network. Depending on the initial conditions, the network will end up in one of the stable states. This can allow pattern completion to occur.

Short-term plasticity

A phenomenon in which synaptic efficacy changes over time in a way that reflects the history of presynaptic activity. The duration of such plasticity varies from a few milliseconds to tens of minutes.

Long-term depression

Long-lasting weakening of synaptic strength between neurons, often resulting from asynchronous presynaptic and postsynaptic activity.

Long-term potentiation

A persistent enhancement of excitatory synaptic transmission lasting from hours to days, triggered by strong, typically high-frequency, afferent stimulation of the synapse. It is widely studied as a putative physiological basis of long-term memory.

Structural plasticity

Morphological changes that are observed in synapses, dendrites or axons following a particular stimulation protocol or a memory paradigm. The morphological changes may have functional consequences.

En passant boutons

From the French for 'passing' and 'button', swellings on an axon that make non-terminal synaptic contacts on another neuron.

Release probability

The probability that a single presynaptic spike will result in the release of a vesicle of neurotransmitter into the synaptic cleft. Release probability is determined by multiple presynaptic factors.

Metaplastic switch

A plastic change that modifies the ability of a synapse to undergo subsequent synaptic plasticity.

Spike-timing dependent plasticity

(STDP). A form of plasticity that results from functional changes in neurons and/or synapses and that depends on the precise timing of action potentials in connected neurons.

Hebbian synaptic plasticity

A form of neuronal plasticity in which a change in a property (often synaptic strength) results from the simultaneous activation (sometimes repetitively) of presynaptic and postsynaptic cells.

Pattern completion

The process through which a memory can be recalled by the presentation of only a subset of the cues that were available during the learning episode. There is evidence that the CA3 subregion of the hippocampus is necessary for animals to achieve pattern completion.

Pattern separation

The process through which small differences in patterns of input activity are amplified as they propagate through a network to create distinct representations.

Remapping

A reorganization in the pattern of place fields corresponding to particular place cells so that they bear no detectable resemblance to the pattern in the original environment. Rate remapping refers to an alteration in the firing rates of place cells that retain place fields in the same locations as before.

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Rebola, N., Carta, M. & Mulle, C. Operation and plasticity of hippocampal CA3 circuits: implications for memory encoding. Nat Rev Neurosci 18, 208–220 (2017). https://doi.org/10.1038/nrn.2017.10

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