Foraging for food in a dangerous world can be risky. Animals must balance food-seeking and predator avoidance, a behavioral and physiological trade-off that is critical for survival (Lima, 1998; Lima and Dill, 1990). Understanding how animals make these behavioral decisions is central to understanding complex natural behaviors and phenotypic plasticity (Dingemanse and Wolf, 2013; Dufty Jr et al., 2002; Hein, 2022). Although researchers have long recognized the hypothalamus-pituitary-adrenal/interrenal (HPA/I) axis as a neuroendocrine mediator of foraging vs. predator-avoidance tradeoffs (Boonstra, 2013; Clinchy et al., 2013; Harris, 2020; Harris and Carr, 2016), the neural substrates and physiological mechanisms underlying this tradeoff remain unclear. The upstream regulator of the HPA/I axis, corticotropin-releasing factor (CRF) (Armario, 2006; Norris and Carr, 2020), is structurally conserved across vertebrates and is released from neurons in the paraventricular nucleus of the hypothalamus (Cardoso et al., 2016; Lovejoy and Balment, 1999). Hypothalamic CRF neurons are potent suppressors of food intake (Qi et al., 2019; Stengel and Taché, 2014) and predator exposure excites these neurons (Chudoba and Dabrowska, 2023; Kim et al., 2019).

Less is known about the role of extrahypothalamic CRF populations, specifically those in the optic tectum (OT) in foraging-predator avoidance tradeoffs (Carr et al., 2010, Carr et al., 2013; Crespi et al., 2004; Prater et al., 2018b, Prater et al., 2020). The OT is homologous to the mammalian superior colliculus (SC), receives multimodal sensory information (auditory, visual, and, in some aquatic organisms, lateral line mechanosensory information), and regulates behavior via projections to premotor areas of the periaqueductal gray and brainstem (Carr, 2015; Deeg et al., 2009; Ewert and Ewert, 1980; Hiramoto and Cline, 2009; Pratt et al., 2016; Zhu and Goodhill, 2023). The OT plays a central role in approach vs. avoidance behavior (Benavidez et al., 2021; Carr, 2015; Comoli et al., 2012; Larsson, 2015; Liu et al., 2022; Suzuki et al., 2019). Specifically, the OT/SC coordinates early and active defense decisions (Bandler et al., 2000; Dean et al., 1989) to maximize foraging and minimize predator encounters (Favaro et al., 2011; Furigo et al., 2010; Stein et al., 1993; Wu and Zhang, 2023) and is critical for inhibiting foraging when predators are present or during a challenging event (Ewert, 1987; Ewert et al., 2001; Maior et al., 2011, Maior et al., 2012). In rodents, cells in the intermediate layers of the superior colliculus drive the motor outputs for attack (via the zona incerta) of prey detected by via visual or mechanosensory (vibrissal) cues (Zhao et al., 2023). While both CRF neurons (Carr et al., 2010; Crespi et al., 2004) and CRF receptors (Calle et al., 2006) have been reported in intermediate tectal layers of anurans, including X. laevis, their physiological role is not known. Based upon their peculiar architecture (Carr et al., 2010) the tectal CRF neurons appear to be pyramidal-like interneurons, but the types of sensory information that they may be intercepting/modulating is not known. Thus, the SC/OT pathway contributes to how prey animals detect and respond to food in the presence of a predator, but the direct mechanisms by which this modulation of food acquisition occurs are not known.

Previously, we have demonstrated that CRF in the OT of anurans influences feeding decisions, particularly under challenging conditions. Juvenile African clawed frogs (Xenopus laevis) reduce feeding in the presence of a predator (Duggan et al., 2016; Islam et al., 2019; Prater et al., 2020) and in response to a noxious stressor (Prater et al., 2018a). Exposure to a noxious stressor (ether vapor) elevated tectal CRF (Prater et al., 2018a) and tectal injection of CRF decreased food intake compared to controls; an effect driven by activation of CRFR1 receptors (Prater et al., 2018b). Our previous data suggest that in X. laevis CRF neurons located within the OT release CRF locally which acts via CRFR1 receptors to reduce feeding.

At present we do not know which sensory cue(s) tectal CRFR1 modulate. The ‘prey’ used in our previous studies was a fresh cube of chicken liver, thus frogs were exposed to visual, olfactory, auditory, and lateral line prey cues simultaneously. Pyramidal-like interneurons within cell layers 6–8 of the anuran OT synthesize CRF (Carr et al., 2010). These neurons have CRF-immunopositive projections, most likely dendrites, that project outward to the most superficial layers of the OT where retinal ganglion cells make their primary synapses (Lazar, 1989). This arrangement suggests that tectal CRF neurons may modulate incoming retinal information about moving prey items (Carr, 2015). This idea is indirectly supported by visual processing data in zebrafish where GR KO fish (with presumably higher CRF) had tectal periventricular neurons that were less responsive to visual cues (Filosa et al., 2016), and our own previous work (Prater et al., 2018a, Prater et al., 2018b, Prater et al., 2020). Here, we test the hypothesis that activation of tectal CRFR1 decreases feeding in response to purely visual prey cues and to a live, multisensory prey item.