Professor Ewert's Toad

About 35 years ago, I was privileged to attend Professor Dr. Jörg-Peter Ewert's seminar at the Institute of Zoology, Johann Wolfgang von Goethe University, in Frankfurt am Main. I was a student at the time. Prof. Ewert paid a visit to tell us about research underway in his laboratory at the University of Kassel on the nerve cell basis of behavior in the common toad Bufo bufo (Ewert, 1992 and 1997). The simplicity of the model caught my eye and remains deeply embedded in my memory to the day.

Behavior
Prof. Ewert and his colleagues had identified two distinct stereotypical behaviors: turning toward an object recognized as prey for catching and turning away in flight from an object recognized as a predator.

The investigators subsequently teased apart the visual cues that led to the opposed behaviors and decomposed the stimuli into the fundamental shapes and features to which the toads respond. Prof. Ewert was able to demonstrate that the toads recognize a cue as prey as long as it moves and is shaped like a thin bar elongated in direction of the movement. When the bar is oriented perpendicular, that is orthogonal to the direction of movement, the toads refrain (Wachowitz and Ewert, 1996). By contrast, if the object is moving and square, it is recognized as a potential predator, and the toads flee.

In 1993, Prof. Ewert produced a fascinating movie on his studies in collaboration with the Institute for Scientific Film (IWF Institut für Wissenschaflichen Film), Göttingen, Germany. The documentary movie can be viewed in three installments with the player below. The first installment demonstrates the visual cues necessary for prey catching.

Image Processing in the Visual System of the Common Toad - Behavior, Brain Function, Artificial Neuronal Net (IWF No. C 1805, 1993) by Prof. Dr. Jörg-Peter Ewert, University of Kassel, Germany, in collaboration with IWF, Knowledge and Media, Göttingen, Germany (courtesy Prof. Ewert).

Nerve Cell Mechanisms
With these observations in mind, the investigators examined the electrical spiking behavior of the nerve cells in the brain that encode the visual information and may explain the toads' decisions (second installment of the documentary).

The most prominent structure processing visual information in the toads' brain is the optic tectum; a layered midbrain structure composed of two hemispheres homologous to the superior colliculus in mammals. The superficial layers of each hemisphere receive input from the retina of the opposite visual hemifield. The retinotectal connections are spatially ordered, establishing a topographic map of the visual field across the tectal hemispheres such that the upper (superior) margin of the visual field is mapped at the midline (medial) of the opposite tectal hemisphere and the outward (temporal) margin of the visual field is mapped toward the animal's tail (caudal)(see Fig. 1 in Gaze and others, 1963). An object moving across the visual field will elicit local nerve cell responses sequentially across the optic tectum, depending on its shape, orientation and direction of movement. Therefore, the timing of local nerve cell excitation originating in the retina and integrated in the tectum constitutes the information instrumental to object recognition.

Recording electrical nerve cell spiking to visual stimulation from fine wire electrodes lowered into the optic tectum, Prof. Ewert and his colleagues could isolate nerve cells that responded only to bars elongated in the direction of movement, suggesting that these cells, called feature detectors, could identify stimulus cues of fundamental importance to the toads' behavior. In further research, the investigators employed metabolic mapping of cerebral activation with the autoradiographic deoxyglucose method of Sokoloff and others (1977) explained in the second installment of the documentary. This functional neuroimaging technique helped localize brain regions activated by the visual stimuli in question.

In addition to the optic tectum, prof. Ewert and colleagues observed nerve cell activation in an adjacent area near the midline called the thalamic pretectal area, or pretectum for short. In toads, this area receives input from the opposite eye and sends output to the optic tectum on the same side. Recordings of local nerve cell spiking activity identified cells that are active during avoidance behavior. One type, labelled TH3 cells, responded particularly vigorously when the toads saw large objects extending perpendicularly to the direction of motion, which could signal potential danger. A second type, labelled TH6, was activated by rapidly expanding objects coming at the animals. Yet another type, labelled TH10, responded to large stationary, obstacle-like objects. The investigators suggested that, in conjunction with nerve cells in the vestibular system that process information on the toads' balance, networks of various types of pretectal nerve cells effect the pursuit of different kinds of protective behavior. When the pretectum was damaged by a lesion, avoidance was absent, while orienting towards prey was enhanced, even to stimuli resembling a threat. Prey selectivity was impaired. By contrast, when the optic tectum was damaged, orienting behavior towards prey ceased (Ewert and others, 1996). In sum, nerve cells in the toads' pretectum and tectum govern the decision on prey catching or predator flight.

Further Exploits
In further studies, Prof. Ewert and colleagues uncovered other brain structures involved in the behaviors discussed above. The neurotransmitter dopamine is known for its role in reward-seeking and addiction. Apomorphine augments dopaminergic action. Glagow and Ewert (1999) observed that the systemic administration of apomorphine enhanced the toads' snapping for prey, while diminishing their oriented turning toward it. Functional neuroimaging showed that apomorphine increases stimulus-related nerve cell activity not only in the optic tectum, but also in structures that have been directly implicated in addictive behavior, that is the nucleus accumbens and the ventral tegmental area. By contrast, decreased nerve cell activity was found in the pretectum governing flight, and the striatum known to play a role in fine motor control of visually-guided behavior. In the limbic system implicated in the processing of emotions, the septum showed increased activation, while activation was decreased in the lateral amygdala involved in fear conditioning and emotional learning.

In addition to dopaminergic system effects on the toads' nerve cell activation and behavior, Prof. Ewert and colleagues examined neuropeptide Y which has been shown to affect food intake, playing a fundamental role in eating disorders and obesity. Pretectal nerve cells that connect to tectal nerve cells contain this neuropeptide. Funke and Ewert (2006) showed that topical application of neuropeptide Y suppressed nerve cell activation in the superficial layers of the optic tectum, even after the administration of apomorphine. The finding suggests an inhibitory role for this neuropeptide in the processing of visual cues, supporting the idea that both excitatory and inhibitory nerve cell inputs interact, and may compete, to effect either prey catching or flight.

Applications
The toad's catch or flight behavior may be rigid and innate. By contrast, the key stimuli that trip the behaviors are adjustable. The toad learns through conditioning. A hand holding a worm is first perceived as threat, but after repeated offerings will be recognized as food, even in the absence of a worm. Using the observed nerve cell responses, Prof. Ewert and colleagues were able to develop models of hypothetical nerve cell behavior in simulated networks and algorithms predicting outcome (Ewert, 1992). The last installment of the documentary ends with a proof of concept, demonstrating the successful implementation of the resulting computer application, guiding an industrial manufacturing robot with optical cues.

Epilogue
Prof. Ewert's research on the neuroethology of toad prey catching and flight provides a striking example of the fashion in which seemingly simple decisions are the result of complex nerve cell interactions. Similar strategies have been used to examine the nerve cell basis of decision making in primates (Jun and others, 2010; Lo and others, 2009), providing insights into our own decisions and whether free will exists.

In extrapolation, the brain-based simulation of nerve cell networks may allow us to develop more effective structures of human organization. When I began to revisit Prof. Ewert's work last February, the news broke on the possible entanglement of the owners of the New York Mets in Bernhard Madoff's Ponzi scheme (see Michael Rothfeld and Chad Bray's post with the title "Madoff Trustee Buzzes Mets" published online in The Wall Street Journal Feb. 5, 2011), as well as the entanglements of J.P. Morgan Chase (see David Caruso and Larry Neumeister's report for Associated Press with the title "Madoff trustee: JP Morgan execs warned of fraud" published online in The Wall Street Journal on Feb. 3, 2011) and Citigroup (see Grant Cool's post with the title "UPDATE 1-Citi tried to hand off Madoff exposure - lawsuit" published online on reuters Feb. 22, 2011). A few weeks ago, members of the Madoff family made their stance on the affair known in published books (Truth and Consequences: Life Inside the Madoff Family, The End of Normal) and media appearances.

The different behaviors of the Madoff clients and collaborators mentioned above suggest that people in large organizations like investment banks seem to interact very much like the nerve cells in the toads' brain. Some facilitate action, while others slam on the brakes. Outcome depends on which party prevails. The decisions the banks eventually took were the result of a constant tug of war between those who sought business with Madoff because of the stellar performance of his funds and those who warned that the risks involved could not be assessed, because Madoff and his associates withheld crucial information. By contrast, small organizations with fewer people may favor less optimal risk evaluation and pounce at the apparent golden opportunity without in-depth evaluation.

Nerve cell networks observed in nature and implemented in modeled simulations may inform us about the types and the number of elements, as well as the weight of their interactions, sufficient and necessary for an organization to successfully carry out its mission. The Madoff experience glaringly demonstrates that it is best practice to entrust wealth not into the hands of one person, but an organization with a long-standing record of responsible decision making, since it does not take a brain lesion to cause one person's ability of making prudent decisions to fail. Yet, the financial crisis of 2008 aptly demonstrates that even such organizations may fail when inhibition does not adequately balance excitation. Confronted with uncertainty, caution dictates to spread the risk.

Acknowledgement
I thank J.-P. Ewert for teaching me about the neuroethology of toads and sharing the movie with me.

References

• Ewert JP (1992) Neuroethology of an object features relating algorithm and its modification by learning. Rev Neurosci 3:45-64.
• Ewert JP (1997) Neural correlates of key stimulus and releasing mechanism: a case study and two concepts. Trends Neurosci 20:332-339.
• Ewert JP, Schürg-Pfeiffer E, Schwippert WW (1996) Influence of pretectal lesions on tectal responses to visual stimulation in anurans: field potential, single neuron and behavior analyses. Acta Biol Hung 47:89-111.
• Funke S, Ewert JP (2006) Neuropeptide Y suppresses glucose utilization in the dorsal optic tectum towards visual stimulation in the toad Bombina orientalis: a [14C]2DG study. Neurosci Lett 392:43-46.
• Gaze RM, Jacobson M, Szekely C (1963) The retino-tectal projection in Xenopus with compound eyes. J Physiol 165:484-499.
• Glagow M, Ewert J (1999) Apomorphine alters prey-catching patterns in the common toad: behavioral experiments and (14)C-2-deoxyglucose brain mapping studies. Brain Behav Evol 54:223-242.
• Jun JK, Miller P, Hernández A, Zainos A, Lemus L, Brody CD, Romo R (2010) Heterogenous population coding of a short-term memory and decision task. J Neurosci 30:916-929.
• Lo CC, Boucher L, Paré M, Schall JD, Wang XJ (2009) Proactive inhibitory control and attractor dynamics in countermanding action: a spiking neural circuit model. J Neurosci 29:9059-9071.
• Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M (1977) The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat.J Neurochem 28:897-916.
• Wachowitz S, Ewert JP (1996) A key by which the toad's visual system gets access to the domain of prey. Physiol Behav 60:877-887.