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

• Published in: Nature reviews. Neuroscience Vol. 18; no. 4; pp. 208 - 220
• Main Authors: Rebola, Nelson, Carta, Mario, Mulle, Christophe
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2017; Nature Publishing Group
• Subjects: 14/19; 631/378/1595/1554; 631/378/2591/2592; 631/378/2591/2594; 631/378/2591/2595; 64/110; 64/60; 9/30; 9/74; Animal Genetics and Genomics; Animals; Behavioral Sciences; Biological Techniques; Biomedicine; CA3 Region, Hippocampal - physiology; Dendrites - physiology; Encoding (Memory); GABAergic Neurons - physiology; Hippocampus (Brain); Life Sciences; Medical examination; Memory; Memory - physiology; Models, Neurological; Neural circuitry; Neural Pathways - physiology; Neurobiology; Neuronal Plasticity - physiology; Neuroplasticity; Neurosciences; Psychological aspects; review-article; Testing
• ISSN: 1471-003X; 1471-0048; 1471-0048; 1469-3178
• DOI: 10.1038/nrn.2017.10

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. The circuitry of the hippocampal CA3 region has long been hypothesized to be well suited to the storage of memories. Mulle and colleagues provide an update on the known types and mechanisms of synaptic plasticity in CA3 and describe evidence for their roles in memory formation and retrieval. 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.