Optogenetic Recruitment of Dorsal Raphe Serotonergic Neurons Acutely Decreases Mechanosensory Responsivity in Behaving Mice

Abstract

The inhibition of sensory responsivity is considered a core serotonin function, yet this hypothesis lacks direct support due to methodological obstacles. We adapted an optogenetic approach to induce acute, robust and specific firing of dorsal raphe serotonergic neurons. In vitro, the responsiveness of individual dorsal raphe serotonergic neurons to trains of light pulses varied with frequency and intensity as well as between cells, and the photostimulation protocol was therefore adjusted to maximize their overall output rate. In vivo, the photoactivation of dorsal raphe serotonergic neurons gave rise to a prominent light-evoked field response that displayed some sensitivity to a 5-HT1A agonist, consistent with autoreceptor inhibition of raphe neurons. In behaving mice, the photostimulation of dorsal raphe serotonergic neurons produced a rapid and reversible decrease in the animals' responses to plantar stimulation, providing a new level of evidence that serotonin gates sensory-driven responses.

The neurobiology of offensive aggression: Revealing a modular view

“…Furthermore, it is time to abandon the simplistic nonspecific neurochemical deficiency models in favor of a specific or selective neurocircuitry deficiency concept (i.e., "neurocircuitopathy"). Its main neurophysiological function seems to be the gating of sensory input and motor output [205,206]. Low levels of serotonin cause the organism to reduce on external input in favor of more intrinsically generated behavior.…”

Motivated state control in larval zebrafish: behavioral paradigms and anatomical substrates

“…For instance, there is considerable evidence that serotonergic signaling from the dorsal raphe has a state-dependent role in modulating responses to sensory cues. Activation of dorsal raphe neurons suppresses neuronal responses to acoustic, olfactory and mechanosensory stimuli (Andersen and Dafny, 1982; Sheibani and Farazifard, 2006; Petzold, Hagiwara and Murthy, 2009; Dugué et al, 2014), although sub-groups of sensory neurons also show increased or prolonged sensory responses during serotonin application (Ebert and Ostwald, 1992; Hurley and Pollak, 1999). Such studies are typically performed without actively controlling the internal state of the animal.…”

Subtraction and division of visual cortical population responses by the serotonergic system

“…More recent studies applied antagonist and agonist of 5-HT via microiontophoresis in the monkey visual cortex, suggesting that 5hydroxytryptamin (5-HT)-receptors are involved in normalization of visual responses (Watakabe et al, 2009;Seillier et al, 2017). However, so far, only studies on somatosensorydriven behavioral responses (Dugué et al, 2014) and in olfactory cortex (Lottem et al, 2016) specifically activated 5-HT neurons in the DRN to trigger the natural and intrinsic spatiotemporal synaptic 5-HT innervation pattern within the target cortical areas. Therefore, to investigate how DRN projections influence sensory processing directly (Davis et al, 1980), in particular, during early cortical steps of fast sensory cortical encoding (Waterhouse et al, 1990;Hurley et al, 2004;Petzold et al, 2009), optogenetic approaches were used (Ranade and Mainen, 2009;Dugué et al, 2014;Lottem et al, 2016).…”

“…However, so far, only studies on somatosensorydriven behavioral responses (Dugué et al, 2014) and in olfactory cortex (Lottem et al, 2016) specifically activated 5-HT neurons in the DRN to trigger the natural and intrinsic spatiotemporal synaptic 5-HT innervation pattern within the target cortical areas. Therefore, to investigate how DRN projections influence sensory processing directly (Davis et al, 1980), in particular, during early cortical steps of fast sensory cortical encoding (Waterhouse et al, 1990;Hurley et al, 2004;Petzold et al, 2009), optogenetic approaches were used (Ranade and Mainen, 2009;Dugué et al, 2014;Lottem et al, 2016). For example, in the somatosensory system optogenetic stimulation of 5-HT neurons in the DRN increased perceptual thresholds for tactile stimuli (Dugué et al, 2014).…”