GAP JUNCTIONS BEYOND DENDRITIC SPINES IN THE MAMMALIAN INFERIOR OLIVE

In the mammalian inferior olive (IO), inter-neuronal communication mediated largely by electrical synapses is a defining characteristic. Connexin36-based gap junctions (GJs) are abundantly expressed in IO neurons, and electrical coupling underlies prevailing theories of the spatiotemporal coordination of cerebellar complex spike activity.
GJs residing on dendritic spines are embedded within specialized microdomains that include nearby GABAergic axon terminals, modulating electrical coupling by the local inhibitory conductance. Consistent with this framework, ultrastructural studies report GJs predominantly on dendritic spines, with somatic GJs described only rarely under hypertrophic or pathological conditions. Consequently, electrical coupling in the IO is widely considered to be confined to spine-based microdomains.
Here, we re-examine this assumption using freeze-fracture replica electron microscopy, allowing direct visualization of GJs, and identify large GJ plaques spanning membrane areas, incompatible with dendritic spine morphology, located on large dendrites and neuronal somata.
Complementary volume electron microscopy of the mouse principal IO reveals frequent regions of extremely close apposition between neighboring somata, as well as extensive contacts between somata and thick, spineless dendrites, often without intervening glial processes. Similar lack of glial separation is observed within tightly intertwined bundles of thick dendrites, providing additional membrane substrates for potential electrical coupling.
Together, these findings indicate that GJ-mediated communication in the IO is not restricted to dendritic spines. Instead, electrical coupling via large dendritic and somatic membranes may be more prevalent than previously appreciated, raising new questions regarding the regulation of coupling strength and the contribution of different coupling architectures contribute to IO network dynamics.