Cerebellin-4 (Cbln-4) signalling mediating memory-guided behaviours

Abstract

Psychiatric and neurodegenerative disorders present with distinct and wide variety of symptoms. Learning and memory impairment is one common cognitive manifestation among these. However, at the molecular and circuitry levels, our knowledge of the neural operations and pathology behind these symptoms is restricted. In this study, we show that presynaptic signalling of Cerebellin4 (Cbln4), a synaptic protein, to the dentate gyrus (DG), are essential in mediating pattern separation ability in mice. This suggests that Cbln4 plays a vital role in encoding and recall of precise memory, via presynaptic signalling to the DG. This disability of Cbln4-mediated pattern separation is interestingly paired with an increased rate of neurogenesis in the DG. We also find that the deletion of Cbln4 in the DG resulted in a reduced frequency of miniature inhibitory post-synaptic currents (mIPSCs) in the dentate gyrus granule cells. However, learning and memory skills tested by a contextual fear conditioning and extinction task remain unimpaired. Altogether, Cbln4 signalling from presynaptic inputs to the DG and within plays a crucial role in preserving the molecular and circuit level accuracy of the memory code, with an experience-dependent modulation of neurogenesis.