Novel effects of CRF on visuomotor behavior and autonomic function in anuran amphibians

doi:10.1016/j.ygcen.2005.09.002

General and Comparative Endocrinology

Volume 146, Issue 1, March 2006, Pages 28-35

https://doi.org/10.1016/j.ygcen.2005.09.002 Get rights and content

Abstract

Administration of corticotropin-releasing factor (CRF) or exposure to stressors inhibits feeding in anuran amphibians. Since most amphibians rely on visual cues for feeding, these findings have led to the hypothesis that CRF may modulate visuomotor pathways involved in prey detection and predator avoidance. The inhibitory effects of CRF on feeding and prey capture are rapid, and do not appear to require the pituitary-adrenal axis in the short term. CRF neurons are located in key visuomotor processing areas of the anuran brain. Corticotropin-releasing factor also has potent stimulatory effects on sympathetic nervous system activity, a key regulatory system involved in both prey capture and predator avoidance. In this review I will discuss the unique model that amphibian species provide for investigating CRF effects on visual perception and visuomotor processing, and will summarize the data suggesting a role for CRF in visuomotor behavior and autonomic function in amphibians.

Introduction

Although corticotropin-releasing factor (CRF) was first isolated and sequenced (Spiess et al., 1981, Vale et al., 1981) for its effects on corticotropin secretion from the pituitary gland (Guillemin and Rosenberg, 1955), it is now known that this 41 amino acid peptide has a wide range of endocrine, neuroendocrine, and paracrine actions both within and outside the central nervous system. The identification of two CRF receptor types has helped to broaden the view of CRF’s physiological role (Dautzenberg and Hauger, 2002), revealing for example the predominance of CRF R2 receptors in many peripheral tissues and wide-ranging effects of peripherally administered CRF and urocortin on the cardiovascular and gastrointestinal systems (Martinez et al., 2004). The recent development of selective CRF receptor agonists and antagonists (Zorrilla et al., 2003) has allowed for a detailed examination of the role of CRF receptors in processes ranging from reproduction to the integration of stress.

Several advances have been made in identifying components of the CRF system in non-mammals, paving the way not only for a detailed examination of how the structure/function relationships of CRF peptides have evolved, but how CRF and urocortin neuronal pathways have tapped into phylogenetically ancient sensorimotor pathways to modulate behavioral decision making. Recent data from amphibians suggest that CRF peptides mediate the inhibitory effects of stressors on visually guided feeding. The question of how CRF influences visual perception and visuomotor processing is broadly applicable to all vertebrates, but can benefit from studies in amphibians in which subcortical visual pathways have evolved under the competing selective pressures of acquiring food and avoiding predators (Carr, 2002). Here I will review recent data from amphibians supporting a role for CRF in modulating visuomotor function and autonomic nervous system activity that accompanies feeding and predator avoidance.

Section snippets

Neural substrates of feeding behavior and predator avoidance in anurans

Most anurans locate their food visually and the recognition of prey occurs entirely through subcortical visual pathways. Neuroethological studies have provided a great deal of information on the functional organization of prey detection pathways (Ewert et al., 2001). Visual information regarding a prey item is sent via retinal ganglion cells to the optic tectum, which integrates this information and initiates a series of behaviors aimed at capturing the prey such as orienting, approaching, and

CRF effects on the autonomic nervous system

Prey catching or predator avoidance both are associated with increased respiratory and cardiovascular activity in amphibians, and several studies indicate that neurons in the optic tectum as well as in the thalamus and pretectal region are capable of driving increased activity of the sympathetic nervous system (SNS) in association with orienting and avoidance behaviors. In mammals, electrical stimulation of the superior colliculus, the homolog of the optic tectum, activates the autonomic

Summary

Recent evidence in amphibians suggests that CRF may act to influence visuomotor circuitry involved in feeding, in effect altering what the animal thinks that it sees. Corticotropin-releasing factor may play an especially important role in gating modulatory pathways that inhibit visually guided feeding in the presence of a threat. Evidence of a role for CRF in visually guided feeding comes from studies showing that exogenous CRF inhibits prey catching and food intake in at least three anuran

Acknowledgments

This review paper was developed from a presentation in a symposium at the 15th International Congress of Comparative Endocrinology in Boston, MA, May 23–28, 2005. I thank Nick Bernier and Robert Denver for organizing the symposium. Many of the students involved in this research have been supported through a Howard Hughes Medical Institute grant through the Undergraduate Biological Sciences Education Program to Texas Tech University.

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For example, when predators are abundant, larval frogs reduce the time spent active and reduce swimming speed in spite of food being available (Anholt et al., 2000), and this pattern suggests that the animals are simultaneously sensitive to risks from predation and gains from feeding (Anholt et al., 2000). Most anuran amphibians locate food visually and recognize the prey via subcortical visual pathways (Carr, 2006). The optic tectum (OT) is critical for visual and mechanosensory detection of prey and threats.
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For example, an organism would be more anxious and possibly responsive to sensory cues which may aid it in being able to adequately respond to threats, but it also must balance this increased “vigilance” with feeding and reproducing. Not only does this idea integrate how predator-induced HPA/HPI axis activation could lead change in organism behavior and fitness, it would help explain the modulatory effect of satiety peptides on sensory input and feed/flee neural networks (Carr, 2002, 2006; Carr et al., 2002). Balancing feed or flee decisions also is bound to affect reproduction because 1) reproduction is energetically expensive and adequate energy reserves are needed to sustain reproduction, and 2) reproduction is often conspicuous and organisms must balance being eaten with copulatory and parental care behaviors.
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A major role for CRF receptor agonists during stress is the inhibition of food intake and appetite, which appears to involve CRF and related peptides interacting with both CRF R1 and R2 receptors at different sites within the CNS (Bakshi et al., 2007; Chen et al., 2010) and periphery (Fekete et al., 2011). We previously suggested (Carr, 2006) an alternative theory to explain CRF effects on food intake that involves direct modulation of sensory cues for recognizing food. This theory is based on data that CRF inhibits visually guided feeding and prey capture in at least three anuran species: the Texas toad (Bufo speciosus) (Carr et al., 2002), the Western spadefoot toad (Spea hammondii) (Crespi and Denver, 2004) and the bullfrog (Rana catesbeiana) (Morimoto et al., 2011).
Previous work indicates that CRF administration inhibits visually guided feeding in amphibians. We used the African clawed frog Xenopus laevis to examine the hypothesis that CRF acts as a neurotransmitter in the optic tectum, the major brain area integrating the visual and premotor pathways regulating visually guided feeding in anurans. Reverse transcriptase PCR revealed that cells in the optic tectum express mRNA for CRF and the CRF R1 receptor but not the CRF R2 receptor. Radioligand binding studies indicated that specific binding of [¹²⁵I]-Tyr-oCRF to tectal cell membranes can be displaced by the CRF R1 antagonists antalarmin or NBI-27914. CRF increased the expression of mRNA encoding regulator of G-protein signaling 2 (rgs2) in tectal explants and this effect was blocked by antalarmin. CRF had no effect on basal glutamate or gamma-aminobutyric acid (GABA) secretion but inhibited secretion of norepinephrine from tectal explants, an effect that completely blocked by antalarmin. Using a homologous radioimmunoassay we determined that CRF release from tectal explants in vitro was potassium- and calcium-dependent. Basal and depolarization-induced CRF secretion was greater from optic tectum than hypothalamus/thalamus, telencephalon, or brainstem. We concluded that the optic tectum possesses a CRF signaling system that may be involved in modulating communication between sensory and motor pathways involved in food intake.
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This has been proposed as a better way to gain insight into the circuitry underlying emotional learning and memory.309,411 As CRF-like peptides and CRF receptors potently modulate stress-related and social behavior,405,412–415 it seems likely that behavioral therapies will also potently affect CRF systems. The use of behavior modification to indirectly evoke or inhibit CRF systems and regulation of stress-adverse reactions may be an effective remedy to bypass the complexity of the system by invoking a preestablished endogenous capacity.
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The superior colliculus fits these criteria in that its homolog (i.e., the optic tectum) is apparent in virtually all vertebrates and appears to be organized similarly to mammalian super colliculi (Gaither and Stein, 1979). In anuran amphibians, the optic tectum is crucially involved in orienting the animal's gaze toward potential prey and then initiating a motor response to this gaze location (Carr, 2006; Ewert et al., 2001; McConville et al., 2006). The superior colliculus may have a similar role in generating signals that are important for the coordination of eye and arm movements in primates.
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Novel effects of CRF on visuomotor behavior and autonomic function in anuran amphibians

Abstract

Introduction

Section snippets

Neural substrates of feeding behavior and predator avoidance in anurans

CRF effects on the autonomic nervous system

Summary

Acknowledgments

Neurosci. Lett.

Gen. Comp. Endocrinol.

Neurosci. Biobehav. Rev.

Brain Res.

Horm. Behav.

Gen. Comp. Endocrinol.

Rev. Comp. Biochem. Physiol. B Biochem. Mol. Biol.

Horm. Behav.

Comp. Biochem. Physiol.

Trends Pharmacol. Sci.

Gen. Comp. Endocrinol.

Horm. Behav.

TINS

Peptides

Gen. Comp. Endocrinol.

Gen. Comp. Endocrinol.

Brain Res.

Neurosci. Lett.

Brain Res. Bull.

Mol. Cell. Endocrinol.

Trends Pharmacol. Sci.

Corticotropin-releasing factor: actions on the sympathetic nervous system and metabolism

Endocrinology

Physiological changes in glucose differentially modulate the excitability of hypothalamic melanin-concentrating hormone and orexin neurons in situ

J. Neurosci.

Responses of single neurons in the toad’s caudal ventral striatum to moving visual stimuli and test of their efferent projection by extracellular antidromic stimulation/recording techniques

Brain Behav. Evol.

Stress, neuropeptides, and feeding behavior: A comparative perspective

Integrative Comp. Biol.

Neuropeptide Y immunoreactivity of a projection from the lateral thalamic nucleus to the optic tectum of the leopard frog

Vis. Neurosci.

Autonomic adjustments during avoidance and orienting responses induced by electrical stimulation of the central nervous system in toads (Bufo paracnemis)

J. Comp. Physiol. [B].