Layer- and cell-type specific effects of serotonin and oscillations on pyramidal cells in the mouse visual cortex
Hugh Takemoto
Team Cortical Circuits

Abstract
In predictive-processing accounts of cortical function, pyramidal cells (PCs) in layer 2/3 (L2/3) are proposed to carry feedforward prediction errors while layer 5 (L5) PCs carry feedback predictions, and neuromodulators and network rhythms are proposed to set the relative weight of these signals. Here I characterised the intrinsic excitability of L2/3 and L5 PCs in the mouse primary (V1) and medial secondary (V2M) visual cortex and asked how it is modulated by serotonin and by theta-band input. I used whole-cell recordings in acute slices with bath-applied serotonin and receptor-selective ligands, genetic labelling of L5 projection classes, and optogenetic activation of afferent input. Under baseline conditions, L2/3 PCs in V2M were more excitable than those in V1, whereas L5 PCs differed in sag, with a trend in resonance, rather than in firing gain. Serotonin increased the afterhyperpolarisation and reduced bursting in all four populations, but its effects on input resistance, firing gain and dendritic excitability (measured through a somatic proxy) were layer- and area- specific, with more effects reaching significance in V2M L5 PCs, the largest cohort; the decreases in Rin, EPSP summation and AHP time were specific to V2M L5. In these cells, pilot experiments suggest that the serotonin-induced reduction in dendritic excitability depends on 5-HT1A receptors and the serotonin-induced increase in resonance frequency may depend on both 5-HT1A and 5-HT2A receptors. Within V2M L5, intrinsic frequency preference separated projection classes: intratelencephalic (IT) cells acted as low-pass filters, whereas extratelencephalic (ET) cells showed theta resonance. Under large-amplitude oscillatory input, ET cells amplified depolarising and hyperpolarising inputs unequally and during suprathreshold 4 Hz drive they advanced their spike phase across cycles. Finally, preliminary findings suggest that long-range input from two top-down inputs (the retrosplenial cortex and orbitofrontal cortex) can increase L5 PC firing during a 4 Hz somatic drive.
Together, these results show that serotonin and theta-band input act through layer- and cell-type-specific intrinsic properties to set how pyramidal cells in the visual cortex integrate their inputs, with L5 ET cells in V2M positioned as selective readers of theta-band input.

Jury
Ede Rancz, Co-directeur de thèse – INMED, Marseille
Laurent Aniksztejn, Co-directeur de thèse – INMED, Marseille
Brandon Stell, Rapporteur – SPPIN, Paris
Carine Bécamel, Rapporteur – IGF, Montpellier
Dirk Jancke, Examinateur – Ruhr University Bochum
Nicolas Wanaverbeq, Président – INT, Marseille

Friday 4 December 2026 at 2.00 pm – INMED conference room