Optogenetic activation of dorsal raphe serotonin neurons induces brain-wide activation

Abstract

Serotonin is a neuromodulator that affects multiple behavioral and cognitive functions. Nonetheless, how serotonin causes such a variety of effects through its brain-wide projections and variety of receptors remains unclear. Here we measured the brain-wide response to optogenetic stimulation of serotonin neurons in the dorsal raphe nucleus (DRN) by functional MRI using an 11.7T scanner with a cryoprobe. Transient activation of DRN serotonin neurons caused wide-spread activation of reward-related brain areas. The same stimulation under anesthesia with isoflurane decreased activation of those reward-related areas and the hippocampal complex. These brain-wide response patterns can be explained by DRN serotonergic projection topography and serotonin receptor expression profiles, with enhanced weights on 5-HT1 type receptors. The primarily facilitatory effect on reward-related brain areas by DRN serotonergic activation is consistent with recent discoveries of its roles in reward-oriented behaviors and demands reconsideration of inhibitory view due to the result under anesthesia.

From neurotransmitters to networks: Transcending organisational hierarchies with molecular-informed functional imaging

“…Another option would be to utilise manipulations of molecular systems within animal models, as recently done by Salvan and colleagues ( Salvan et al, 2022 ) to show that pharmacological and optogenetic manipulation of the serotonergic system modulates the SRNs in a receptor sub-system-specific manner. A similar study has also recently shown that the serotonin receptor gene expression patterns explain a large proportion of the variance in the BOLD signal following optogenetic stimulation of the dorsal raphe ( Hamada et al, 2022 ). Future methodological work expanding the scope of this approach beyond serotonin will be an important step forward to inspect construct validity across neurotransmitter systems.…”

From Neurotransmitters to Networks: Transcending Organisational Hierarchies with Molecular-informed Functional Imaging

“…Another option would be to utilise manipulations of molecular systems within animal models, as recently done by Salvan and colleagues (Salvan et al, 2022) to show that pharmacological and optogenetic manipulation of the serotonergic system modulates the SRNs in a receptor sub-system-specific manner. A similar study has also recently shown that the serotonin receptor gene expression patterns explain a large proportion of the variance in the BOLD signal following optogenetic stimulation of the dorsal raphe (Hamada et al, 2022). Future methodological work expanding the scope of this approach beyond serotonin will be an important step forward to inspect construct validity across neurotransmitter systems.…”

High-resolution awake mouse fMRI at 14 Tesla

“…Since increasing spatiotemporal resolution leads to a reduction in SNR of the images, accessing the highest field MRI available, as well as maximizing the efficiency of the Radio Frequency (RF) transceiver signal is critical. Although cryoprobes have been well implemented to boost SNR, construction limitations of the superconducting environment constrain the usable space and flexibility to accommodate other imaging/recording modalities(13, 67–72). Implantable coils have been used in animal imaging for over three decades(12, 73–79).…”