5-HTR 2A and 5-HTR 3A but not 5-HTR 1A antagonism impairs the cross-modal reactivation of deprived visual cortex in adulthood

• Published in: Molecular brain 2018-11, Vol.11 (1), p.65
• Main Authors: Lombaert, Nathalie, Hennes, Maroussia, Gilissen, Sara, Schevenels, Giel, Aerts, Laetitia, Vanlaer, Ria, Geenen, Lieve, Van Eeckhaut, Ann, Smolders, Ilse, Nys, Julie, Arckens, Lutgarde
• Format: Article
• Language: English
• Subjects: Aging - physiology; Animals; Disease Models, Animal; Eye Enucleation; Female; Male; Mice, Inbred C57BL; Neuronal Plasticity - drug effects; Receptor, Serotonin, 5-HT1A - metabolism; Receptors, Serotonin - metabolism; Receptors, Serotonin, 5-HT2 - metabolism; Receptors, Serotonin, 5-HT3 - metabolism; Serotonin - metabolism; Serotonin 5-HT2 Receptor Antagonists - pharmacology; Serotonin Antagonists - pharmacology; Signal Transduction - drug effects; Synapses - drug effects; Synapses - metabolism; Time Factors; Vesicular Monoamine Transport Proteins - metabolism; Visual Cortex - drug effects; Visual Cortex - physiopathology
• ISSN: 1756-6606
• DOI: 10.1186/s13041-018-0404-5

Visual cortical areas show enhanced tactile responses in blind individuals, resulting in improved behavioral performance. Induction of unilateral vision loss in adult mice, by monocular enucleation (ME), is a validated model for such cross-modal brain plasticity. A delayed whisker-driven take-over of the medial monocular zone of the visual cortex is preceded by so-called unimodal plasticity, involving the potentiation of the spared-eye inputs in the binocular cortical territory. Full reactivation of the sensory-deprived contralateral visual cortex is accomplished by 7 weeks post-injury. Serotonin (5-HT) is known to modulate sensory information processing and integration, but its impact on cortical reorganization after sensory loss, remains largely unexplored. To address this issue, we assessed the involvement of 5-HT in ME-induced cross-modal plasticity and the 5-HT receptor (5-HTR) subtype used. We first focused on establishing the impact of ME on the total 5-HT concentration measured in the visual cortex and in the somatosensory barrel field. Next, the changes in expression as a function of post-ME recovery time of the monoamine transporter 2 (vMAT2), which loads 5-HT into presynaptic vesicles, and of the 5-HTR and 5-HTR were assessed, in order to link these temporal expression profiles to the different types of cortical plasticity induced by ME. In order to accurately pinpoint which 5-HTR exactly mediates ME-induced cross-modal plasticity, we pharmacologically antagonized the 5-HTR , 5-HTR and 5-HTR subtypes. This study reveals brain region-specific alterations in total 5-HT concentration, time-dependent modulations in vMAT2, 5-HTR and 5-HTR protein expression and 5-HTR antagonist-specific effects on the post-ME plasticity phenomena. Together, our results confirm a role for 5-HTR in the early phase of binocular visual cortex plasticity and suggest an involvement of 5-HTR and 5-HTR but not 5-HTR during the late cross-modal recruitment of the medial monocular visual cortex. These insights contribute to the general understanding of 5-HT function in cortical plasticity and may encourage the search for improved rehabilitation strategies to compensate for sensory loss.