Trisynaptic

Trisynaptic refers to the classical three-synapse pathway within the hippocampus that conveys information from the entorhinal cortex to the CA1 region through successive hippocampal subfields. The circuit begins with the perforant path, projections from the entorhinal cortex to dentate gyrus granule cells. From there, dentate granule cells communicate with CA3 pyramidal neurons via mossy fiber synapses. The final relay is a connection from CA3 pyramidal neurons to CA1 pyramonal neurons through Schaffer collateral synapses. While the core loop is the three-synapse sequence, the hippocampus also contains additional connections that interact with this loop, including direct projections from entorhinal cortex to CA1.

Functionally, the trisynaptic circuit is central to hippocampal processing of memory. The dentate gyrus is thought to support pattern separation, transforming similar inputs into distinct representations, while CA3 provides an autoassociative network that can support pattern completion. CA1 receives processed information and integrates it for downstream output to other brain regions. Synaptic plasticity within this circuit, particularly long-term potentiation at the perforant path, mossy fiber, and Schaffer collateral synapses, is a widely studied cellular mechanism linked to learning and memory formation.

Clinical relevance is tied to the integrity of this pathway. Disruption of entorhinal input or hippocampal subfields can impair the encoding of new memories and spatial navigation, and alterations in this circuitry are observed in conditions such as temporal lobe epilepsy and early stages of Alzheimer's disease. The trisynaptic circuit remains a foundational concept in discussions of hippocampal function and memory.