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Showing posts with label nerve cell networks. Show all posts
Showing posts with label nerve cell networks. Show all posts

Wednesday, December 21, 2011

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

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Posted by Peter Melzer at 11:34 AM 2 comments

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Monday, October 12, 2009

The Quest for the Infrasound Acoustic Fovea

In my post dated Sep. 30, 2009, I briefly discussed the discovery of echolocation as a means for bats to navigate their environment in total darkness and identify insects to feast on. I noted that in echolocating bats a large part of the auditory system is devoted to the processing of ultrasound, that is frequencies higher than the human audible (>20 kHz).  A disproportionate number of auditory nerve cells are tuned to analyze the frequencies of the echos of the echolocation calls bats emit. I worked on research with echolocating bats in Gerhard Neuweiler's laboratory at the Institute of Zoology of the Johann Wolfgang Goethe University, Frankfurt am Main. I helped show that exposing a bat to its echolocation frequency activated prominent regions in its auditory midbrain structure known as inferior colliculus (Melzer, 1985). The proclivity in the bat auditory system for a narrow band of ultrasound used for echolocation is known as high frequency filter or acoustic fovea (Neuweiler and others, 1980).

As informative contrast to the bats' fovea for extremely high pitch, a mammal was sought with a fovea for extremely low pitch. It was hoped that a similar association between behaviorally relevant sound and its representation in the brain might exist in species whose hearing is particularly sensitive to infrasound, that is at frequencies beneath the human audible (<20 Hz). Elephants (Herbst and others, 2012) and humpbacked whales are known to produce and hear infrasound, but were considered difficult to study.

By contrast, burrowing rodents were thought to constitute suitable candidates, because they spend much of the day underground and were observed to be able to use seismic vibrations to identify and locate conspecifics and predators. Particularly, gerbils were of interest. They are essentially crepuscular, that is most active above ground at dawn and dusk. They live in semi-arid deserts where compacted gravel and sand carry low frequency sound long distances. Gerbils use hind foot drumming as means of communication. The drumming exhibits species-specific differences and has been observed to alert companions to one's own presence in as much as to approaching predators (Randall, 1997). Differences in the signature of the sound may permit the animals to distinguish between various types of predator, e.g. snakes or birds. Moreover, the sounds may convey to predators that they have been discovered (Randall, 2001).

Christian Winter recruited Jürgen Möller as a junior faculty member to investigate whether gerbils may represent the small mammals with an acoustic fovea for infrasound. He had extensive experience in acoustics, micro-electrode recordings of electrical nerve cell discharges, and animal behavior.

courtesy J. Möller
In addition to the well-known Mongolian gerbil (Meriones unguiculatus), Jürgen succeeded in bringing a number of gerbil species from Israel to the laboratory, testing their hearing for low frequency sensitivity with audiograms. Field studies on the animals' behavior were conducted in Israel.

The photograph depicts a sand rat (Psammomys obesus) in the Negev desert at dusk. Sand rats were the largest gerbils in Jürgen's collection.  Power density spectra of their drumming's acoustic frequency components were recorded to examine whether the drumming produced infrasound. Broad spectrum audiograms were constructed from recordings of small voltage changes in the inner ear (cochlear microphonics) and from nerve cell activity in the auditory midbrain (inferior colliculus) to investigate whether the animals could hear infrasound.

The results were presented at a joint symposium of Hebrew University of Jerusalem, Université de Lyon, and Johann Wolfgang von Goethe University entitled "Neurobiology and Strategies of Adaptation". The symposium was convened in Frankfurt am Main in 1981. The two figures below show representative results of the frequencies of the sound produced by drumming (A) and of the sound processed by the auditory system (B). The green band covers the frequency range between 0.5 and 1.0 kHz in which the audiograms (B) show peculiar low frequency sensitivity.

(A) Power Density Spectrum
The frequency of the drumming's acoustic components [kHz] (y-axis) is plotted versus time [ms] (x-axis; courtesy J. Möller).

(B) Audiograms
The sound pressure level [dB SPL] of the most sensitive response (y-axis) is plotted versus sound frequency [kHz] (x-axis). Cochlear microphonics: CM; nerve cell responses in the inferior colliculus: IC (courtesy J. Möller).
Analysis of the power spectra revealed that the animals' drumming contained low frequencies of significant power, infrequently dipping into infrasound. Yet, the audiograms of the animals provided no evidence of an acoustic fovea for such low frequencies. Regardless, the findings clearly suggested that the drumming produced sound to which that the animals' hearing was sensitive.

My project's aim was to visualize pitch-related nerve cell activation in the brain with a functional imaging method (Melzer, 1984). M. Müller (now private docent at the J.W. Goethe University) helped me substantially in this endeavor. The project would not have been possible without the use of the whole-body cryotome in H.-M. Kellner's division at the Hoechst AG's Radiochemical Laboratory.

Animals were exposed to sound of low, medium and high pitch. Pitch is represented tonotopically on the transverse plane through the inferior colliculus. That is, nerve cells in the upward (dorsal) aspect of the structure are particularly sensitive to low frequency sound and become progressively more sensitive to higher frequencies with increasing depth. Functional imaging would reveal the isofrequency domains, permitting us to assess the prominence of low frequency processing in the auditory system.

The figure below shows frequency-related nerve cell activation in transverse slices through the inferior colliculus. Nerve cell activation is coded in pseudo colors (blue: low; red: high). The narrow blue/purple lines near the top are the animals' scalp, that is dorsal is up. The brainstem is at the bottom, that is ventral is down. The animals' left side is on the right.

Neurofunctional Images
The slices were obtained from sand rats exposed to tone pips of (clockwise from top, left) 0.8, 2.5 and 17.0 kHz, respectively. Stimulus-unrelated nerve cell activity was obtained from unexposed animals (bottom, left). The inferior colliculus is the distinctly sound-activated, double-lobed structure at the center of the images. Unexposed animals revealed slightly elevated nerve cell activity in the top aspect of the structure on both sides (bottom, left). Low frequency stimulation produced wide-spread activation, peaking in a band at the top of the structure (top, left). This activation partially overlapped with the observed stimulus-unrelated activity (bottom, left). By contrast, the middle frequency activated a narrow band at mid-depth of the structure on both sides (top, right), whereas activity at the top was almost completely suppressed. High frequency stimulation resulted in similarly narrow bands of activation on both sides. Only in this case, the bands were located at the bottom of the inferior colliculus (bottom, right). In addition, prominent activity was distinct at the top of the structure.

The progression of bands of elevated nerve cell activation from top to bottom with increasing frequency of stimulation is consistent with the notion of a tonotopic map where frequencies are represented in logarithmic progression. Intriguingly, the low part of the sound spectrum was slightly disproportionally represented. However, such disproportionality is not uncommon and has been observed in a number of species (N. Suga, personal communication).

The narrow bands of activation observed with the middle stimulus frequency conformed most distinctly with a representation of frequencies in discrete isofrequency layers. According to the cochlear microphonics, the animals' ear is most sensitive at this frequency. By contrast, the wide-spread activation at the low frequency and the additional foci at the top of the inferior colliculus at the low and the high frequency did not precisely adhere to the principle of discrete frequency representation. We did not know how to interpret these results.

In hindsight, we were perhaps too narrowly focused on auditory responses. Parts of the inferior colliculus are known to receive somatic sensory input. Sand rats have long mystacial whiskers that are in frequent contact with the soil. Cytoarchitectonic structures known as barrels represent the mystacial whiskers topographically in a large swath of the gerbil's cerebral somatic sensory cortex (Rice and others, 1985). Distinct septa separate the barrels. Nerve cells in the septa are known to be particularly attuned to the processing of stimulus frequency (Melzer and others, 2006). Recent observations show that whiskers may resonate (Moore, 2004) to low frequency vibrations, touch receptors in the whisker follicles transduce frequencies up to 1.0 kHz and possibly greater (Gottschaldt and Vahle-Hinz, 1981), and nerve cells in the somatic sensory pathway may process this information (Kleinfeld and others, 2006). Perhaps, gerbils do possess an infrasound fovea after all! Only the processing of this sound may not be strictly auditory.

Addenda
  • Watching gerbils around the time of an earthquake may prove insightful. A tiny whiskered burrowing rodent, the Northern Pocket Gopher Thomomys talpoides, survived the catastrophic eruption of Mt. St. Helens in 1980 (11/06/09).
  • Caldwell and others (2010) produced an impressive demonstration of the importance of vibrations in vertebrate sensation and behavior. The research feature on National Public Radio's Talk of the Nation (Science Friday) yesterday with the title "Rumble in The Jungle" shows red-eyed treefrogs (Agalychnis callidryas) from the rain forests of central America communicating with vibrations mediated by the twig they sit on. Listen to the podcast of Ira Flatow's conversation with Flora Lichtman entitled "Red-Eyed Treefrogs Rumble in the Jungle". The authors of the study, affiliated with Boston University, contributed excellent footage of the frogs' interactions (05/22/10).
  • On Apr. 8, 2011, National Public Radio's Talk of the Nation/Science Friday broadcast an insightful segment with the title "Seeing The World Through Whiskers" on the research of Mitra Hartman and her colleagues (Towal and others, 2011) examining whisking in rats with high-speed video (04/11/2011):
  • The magnitude 5.8 earthquake on the East Coast on Aug. 23, 2011, centered near Mineral, Virginia, was felt roughly 120 miles away by animals of the National Zoo in Washington D.C., in some instances tens of minutes before humans did. Listen to Ira Flatow's interview with Brandie Smith, Senior Curator of the National Zoological Park, Smithsonian Institution, Washington D.C., entitled "Did you feel it?" on National Public Radio's Talk of the Nation/Science Friday broadcast today (08/26/2011).
  • Listen to Dr. Tecumseh Fitch explaining to Audie Cornish of National Public Radio's All Things Considered in his interview with the title "Study: Humans, Elephants User Similar Vocalizations" broadcast today how elephants produce and may use infrasound (08/09/2012).
References
Footnote
  • The text of this post is available for download in pdf-format from the scribd store.
Related Posts
I attached this amateur video of a pet gerbil drumming in the cage. The clip provides an idea of drumming speed and periodicity. Keep in mind that a gerbil in a burrow will sound quite different.




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Posted by Peter Melzer at 6:02 AM 0 comments

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