Work

Pattern separation memory requires Cerebellin 4 – Neogenin 1 signaling at dentate gyrus synapses

Year: 2026

Type: article

Abstract: The ability to avoid confusion between similar episodic memories enables organismal survival and fitness. This evolutionarily conserved differentiation process of memories as distinct representations is known as pattern separation. A central role for the entorhinal cortex→dentate gyrus (EC→DG) circuit in pattern separation memory is well established, but the molecular mechanisms that enable this circuit to mediate pattern separation memory are incompletely understood. We previously found that a trans-synaptic protein complex formed by presynaptic Cerebellin-4 and postsynaptic Neogenin-1 is selectively required for long-term potentiation (LTP) in the EC→DG circuit. We now demonstrate that this complex is essential for normal pattern separation memory, suggesting a role for this form of LTP in pattern separation memory. Deletion of either presynaptic Cerebellin-4 in the entorhinal cortex or of postsynaptic Neogenin-1 in the dentate gyrus impaired pattern separation but did not affect pattern completion memory. Thus, we describe a specific memory function for a defined molecular complex at an identified synapse, providing direct support for the hypothesis that synaptic plasticity contributes to the encoding of memory.

Source: Progress in Neurobiology

DOI: 10.1016/j.pneurobio.2026.102917