Shared rhythmic subcortical GABAergic input to the entorhinal cortex and 1 presubiculum 2 3

1 Shared rhythmic subcortical GABAergic input to the entorhinal cortex and 1 presubiculum 2 3 Tim J. Viney*, Minas Salib, Abhilasha Joshi, Gunes Unal, Naomi Berry, Peter Somogyi*. 4 5 Department of Pharmacology, University of Oxford, Oxford, OX1 3QT, UK. 6 7 Rhythmic theta frequency (~5-12 Hz) oscillations coordinate neuronal synchrony and higher frequency 8 oscillations across the cortex. Spatial navigation and context-dependent episodic memories are 9 represented in several interconnected regions including the hippocampal and entorhinal cortices, but the 10 cellular mechanisms for their dynamic coupling remain to be defined. Using monosynaptically-restricted 11 retrograde viral tracing in mice, we identified a subcortical GABAergic input from the medial septum 12 that terminated in the entorhinal cortex, with collaterals innervating the dorsal presubiculum. 13 Extracellularly recording and labeling GABAergic entorhinal-projecting neurons in awake behaving 14 mice show that these subcortical neurons, named orchid cells, fire in long rhythmic bursts during 15 immobility and locomotion. Orchid cells discharge near the peak of hippocampal and entorhinal theta 16 oscillations, couple to entorhinal gamma oscillations, and target subpopulations of extra-hippocampal 17 GABAergic interneurons. Thus, orchid cells are a specialized source of rhythmic subcortical GABAergic 18 modulation of ‘upstream’ and ‘downstream’ cortico-cortical circuits involved in mnemonic functions. 19