Functional Autapses Selectively Form in a Subpopulation of Subicular Pyramidal Cells in Hippocampal Formation

Autapses are self-synapses formed by a single neuron. They selectively form in a subpopulation of neocortical glutamatergic pyramidal cells (PCs) where autaptic transmission provides strong feedback regulation of self-activity in individual neurons. PCs in the hippocampal formation (HPF) possess morphological and electrophysiological characteristics similar to neocortical PCs; it remains unclear, however, whether they form functional autapses. We performed whole-cell recording from HPF PCs in acute slices obtained from mice of either sex and found surprisingly that none of the recorded PCs in CA1-3 show autaptic responses; only a subpopulation of PCs (∼50%) in the subiculum forms functional autapses, particularly those targeting to the nucleus accumbens. Further experiments reveal that the autaptic responses in subicular PCs are mediated solely by AMPA receptors but not NMDA receptors and occur much earlier than those of the medial prefrontal cortex during early development. Together, the results indicate that functional autapses selectively form in a considerable subset of subicular PCs but are completely absent from PCs in the hippocampus proper, suggesting a key role of autapses in regulating the self-activity of subicular PCs and thus the main output signals of the hippocampus.