Autapses in the Neocortex: Discovery of Neuronal Self-Synapses

Van der Loos H, Glaser EM. Autapses in neocortex cerebri: synapses between a pyramidal cell’s axon and its own dendrites. Brain Res 1972;48:355-360. doi: 10.1016/0006-8993(72)90189-8.

Background: This study describes a previously unrecognized synaptic phenomenon in the neocortex, in which a neuron forms a synapse with its own dendrite. The authors introduced the term “autapse” to denote such self-synaptic contacts. This work arose from a long-term analysis of cortical circuitry using Golgi preparations of rabbit occipital cortex, during which these surprising synaptic arrangements were observed between pyramidal cells’ axon collaterals and their own basal dendrites.

Hypothesis: This study hypothesized that autapses represent a biologically meaningful feedback mechanism, allowing neurons to regulate their own dendritic input through inhibitory self-synapses, thereby gating part of their excitatory input and modifying the neuron’s impulse generation.

Methods: The authors examined Golgi-impregnated pyramidal cells from rabbit occipital cortex using a computer-assisted neuron reconstruction method they had developed previously – a semi-automatic “computer microscope” capable of tracking neuronal processes in three dimensions with micrometer precision. Twelve neurons were fully reconstructed to map their synaptic connections.

Results: Six of the twelve analyzed neurons possessed autapses, totaling fourteen such contacts. These occurred mainly on second- to fourth-order basal dendrites, at mean axonal distances of 169 μm from the soma, forming loops averaging 272 μm in length. Autapses appeared as either punctiform or climbing fiber arrangements, involving boutons terminaux or de passage.

Conclusions: The authors concluded that autapses are genuine structural features of neocortical pyramidal neurons and may serve as self-regulatory inhibitory circuits. They proposed that autapses could function as local gating mechanisms and recommended ultrastructural verification by electron microscopy to elucidate their morphology and prevalence across species.