A BIHEMISPHERIC CIRCUIT MECHANISM UNDERLIES ALTERNATING THETA SWEEPS IN PARAHIPPOCAMPAL NETWORKS

Navigation relies on entorhinal–hippocampal circuit dynamics, including theta sweeps, where decoded positions from medial entorhinal cortex (MEC) grid cells alternately extend to the left and right of the animal’s current location on successive theta cycles. These sweeps are guided by an internal direction (ID) signal in parasubiculum (PaS) that alternates sides across theta cycles and is phase-shifted (~30-degrees) relative to upstream head-direction (HD) inputs, raising the question: How are HD inputs transformed to ID signals?
Using Neuropixels 2.0 recordings from MEC/PaS in rats, we identify conjunctive “HD×ID” cells in PaS that may enable this transformation, analogous to circuits described in Drosophila. These cells exhibit strong HD tuning, theta-cycle skipping, and hemispheric lateralization: left-hemisphere cells fire during rightward sweeps and show a clockwise shift of ID tuning relative to HD tuning, while right-hemisphere cells show the opposite pattern. Cross-correlogram analyses reveal monosynaptic connections from HD×ID to ID cells in both hemispheres, with tuning offset distributions centered around ~30-degrees.
Based on this hemispheric asymmetry and phase-offset connectivity, we propose that HD×ID cells in the two hemispheres receive copies of the HD signal and reciprocally inhibit each other, forming a central pattern generator (CPG)-like circuit that alternately biases rightward and leftward theta sweeps. Consistent with this, hemispheric inactivation of MEC/PaS via CaMKIIα inhibitory DREADDs biases theta sweeps and ID signal contralaterally. Together, these results identify a CPG-like mechanism in higher-order cortices, suggesting that fundamental algorithms are conserved across circuits, species, and extend to cognitive computations such as navigation.