TMT-Opsins differentially modulate medaka brain function in a context-dependent manner

Abstract

Vertebrate behavior is strongly influenced by light. Light receptors, encoded by functional opsin proteins, are present inside the vertebrate brain and peripheral tissues. This expression feature is present from fishes to human and appears to be particularly prominent in diurnal vertebrates. Despite their conserved widespread occurrence, the nonvisual functions of opsins are still largely enigmatic. This is even more apparent when considering the high number of opsins. Teleosts possess around 40 opsin genes, present from young developmental stages to adulthood. Many of these opsins have been shown to function as light receptors. This raises the question of whether this large number might mainly reflect functional redundancy or rather maximally enables teleosts to optimally use the complex light information present under water. We focus on tmt-opsin1b and tmt-opsin2, c-opsins with ancestral-type sequence features, conserved across several vertebrate phyla, expressed with partly similar expression in non-rod, non-cone, non-retinal-ganglion-cell brain tissues and with a similar spectral sensitivity. The characterization of the single mutants revealed age- and light-dependent behavioral changes, as well as an impact on the levels of the preprohormone sst1b and the voltage-gated sodium channel subunit scn12aa. The amount of daytime rest is affected independently of the eyes, pineal organ, and circadian clock in tmt-opsin1b mutants. We further focused on daytime behavior and the molecular changes in tmt-opsin1b/2 double mutants, and found that—despite their similar expression and spectral features—these opsins interact in part nonadditively. Specifically, double mutants complement molecular and behavioral phenotypes observed in single mutants in a partly age-dependent fashion. Our work provides a starting point to disentangle the highly complex interactions of vertebrate nonvisual opsins, suggesting that tmt-opsin-expressing cells together with other visual and nonvisual opsins provide detailed light information to the organism for behavioral fine-tuning. This work also provides a stepping stone to unravel how vertebrate species with conserved opsins, but living in different ecological niches, respond to similar light cues and how human-generated artificial light might impact on behavioral processes in natural environments.

Spherical arena reveals optokinetic response tuning to stimulus location, size, and frequency across entire visual field of larval zebrafish

“…Genetic zebrafish variants with altered photoreceptor distributions would thus be a valuable tool for further studies. Recent studies suggest that melanopsin-expressing ganglion cells also contribute to form vision ( Allen et al, 2019 ; Lucas et al, 2020 ), and melanopsins as well as a plethora of other opsins are expressed in the zebrafish retina and brain ( Davies et al, 2015 ; Fontinha et al, 2021 ). It is therefore possible that photoreception via opsin-expressing neurons in the inner retina contributes to zebrafish OKR as well.…”

Adenylate kinase 1 overexpression increases locomotor activity in medaka fish

“…The tracking profiles showed that both Ak1-OE and WT larvae were more active during the light phase than during the dark phase (Fig 2B). Compared to that on the first day of the assay, the total distance moved by the WT larvae significantly decreased on the third day (Fig 2C [14,15], larvae were not fed during the assay to avoid interrupting it. This may have caused decreased energy, and hence, decreased activity, later in the experiment.…”

“…Additionally, there are well-established methods for transgenic and genomic editing in medaka. Behavioral assays are also well established, for both medaka and zebrafish, but medaka can survive a wider range of water temperatures (4-40 °C) than zebrafish (20-32 °C), and they exhibit seasonal behavioral patterns [13][14][15][16]. Therefore, the medaka is an excellent model with which to investigate adaptive strategies to environmental changes.…”

Characterization of tmt-opsin2 in Medaka Fish Provides Insight Into the Interplay of Light and Temperature for Behavioral Regulation

“…Pelagic fish, in particular, possess a whole array of non-visual opsins, e.g., ∼25 opsin genes in Neoteleosts, to which the clade medaka fish belong, and even 42 opsin genes in Zebrafish, making them "swimming photoreceptors" (Davies et al, 2015;Beaudry et al, 2017). We have recently investigated the single and combined genetic removal of two nonvisual opsins of the teleost multiple tissue (TMT) opsin group (Fontinha et al, 2021). In this study, we provide further detailed behavioral analyses of one of the two, tmt-opsin2, especially in the context of different light and temperature conditions, in order to start to obtain deeper insight into the interactions of different environmental parameters.…”

“…TMT-opsins are subdivided again into three classes, TMT opsins 1, 2, and 3. Classes 1 and 2 are blue light-sensitive Gi/Go-coupled receptors, which have been found in known photoreceptive sites of the brain, as well as novel unexpected brain areas, like inter and motor neurons of the mid-and hindbrain (Fontinha et al, 2021;Sato et al, 2021). We have previously started to investigate the functional roles of tmt-opsin1b and tmt-opsin2, which share expression pattern characteristics (Fischer et al, 2013;Sato et al, 2021) and spectral sensitivity (Sakai et al, 2015).…”