Appropriate axonal pathfinding is a necessary step for the function of neuronal circuits. The mossy fibers (MFs) in the hippocampus of CaMKIIα heterozygous knockout (CaMKIIα-hKO) psychiatric model mice project onto not only the stratum lucidum but also the stratum oriens region in the CA3, which is a projection pattern distinct from that in normal mice. Thus, we examined the electrophysiological properties of the MF-CA3 connection in this mutant mouse on field recordings and found a lower synaptic connection. This study suggested that the phenotype of abnormal MF pathfindings could induce aberrant neuronal functions, which may link to cognition and memory.Key words mossy fiber; immature dentate gyrus; field recording; infrapyramidal bundle; stratum oriens; psychiatry Therapeutic interventions for psychiatric disorders such as schizophrenia (SCZ) are hampered by a lack of clear molecular signatures underlying the pathophysiology of the disorders. However, several studies point to abnormal neuronal connectivity in the hippocampus, which potentially relates to the cognitive impairments observed in SCZ patients.1) The abnormal hippocampal synaptic transmission found in SCZ patients could result from inappropriate neuronal connectivity.Appropriate axonal guidance has to be established during development and maintained throughout life to coordinate neural circuits and their functions. Mossy fibers (MFs), which are axons of granule cells in the dentate gyrus (DG), innervate to the CA3 subregion, forming a hippocampal circuit between DG and CA3. During postnatal development, MFs extend to both the stratum lucidum (SL) and the stratum oriens (SO), forming supra-pyramidal bundles (SPB) and infra-pyramidal bundles (IPB), respectively. The formation of IPB, however, is transient and undergoes pruning during development, leaving mostly SPB upon maturation.2) It is of note that some pathological conditions such as temporal lobe epilepsy result in ectopic formation of IPB.3) The CaMKIIα heterozygous knockout (CaMKIIα-hKO) mouse is considered one of the psychiatric model mice as they showed hyper locomotor activity, the deficits of working memory and social interaction, 4,5) which also have the ectopic MF projection in SO. 6) In the present study, we investigated the electrophysiological properties in the MF-CA3 connection in CaMKIIα-hKO mice to characterize the functional abnormalities of the ectopic MF distribution.
MATERIALS AND METHODSTwo-to four-month-old male mice (age-matched littermates) were used for the experiments. CaMKIIα-hKO mice were generated and maintained in a C57BL6/N tac background 7)