Orgies smell bad

In the jungle of scents

A person can identify thousands of smells and keep them in mind. This is an astonishing achievement for a sense that has always been considered a "lower" sense. How we perceive scents at all - whether seductive or repulsive - turned out to be a mystery difficult to solve scientifically: no sense has remained as shrouded in mystery as the sense of smell. Hannah Monyer from the Interdisciplinary Center for Neuroscience explains what happens in the brain at the cellular and molecular level when we realize a scent, and looks at the role that supposedly secondary meaning plays in philosophy and literature.

Although it is not finally clear how reality is perceived and represented, there is no doubt about where this happens: Perception takes place in the brain, and information about the outside world is received by the brain through the five senses of sight, hearing, touch, smell and taste.

For all senses it is true that genetic determination as well as environmental influences and learning determine our perceptions. In some cases, the regions of the brain in which sensory impressions are processed are structured very differently. Nevertheless, fundamental knowledge about how perception is processed in a specific brain region can often be transferred to other brain regions. My working group is concerned with the question of which genetic and epigenetic factors determine perceptual processes and learning in the brain. Our work, which is carried out on the rat or mouse model, has mostly been carried out specifically on different brain structures in recent years. The practical reason for this is that some areas of the brain are more suitable for certain questions and that previous knowledge already dictated the questions.

Our approach is multidisciplinary: First, we examine the function of a nerve cell and correlate its properties with the gene expression of the cell in question, i.e. determine which genes in the cell are read and translated into proteins. This genetic information supplements anatomical studies: What does the cell look like, where are the key communication channels? Next, we investigate how a particular cell communicates with its neighboring cells and what properties synapses have - those specialized structures through which communication between nerve cells takes place. An important question is: How efficiently are neurotransmitters, chemical messengers, released? All of this information now flows into a computer model: the nerve cells of an artificial network are equipped with the properties that we and other research groups have determined experimentally. The nerve cell networks in the computer model indicate parameters that are essential and determining for a certain "behavior" of the network. Finally, on the basis of the experimental data and the computer models, we formulate hypotheses, the validity of which is then tested in biological systems. In genetically modified mice, for example, the opening times of certain nerve cell channels in selected cell populations can be changed in a targeted manner. Subsequent electrophysiological studies confirm or reject the computer-aided hypotheses. Perhaps one of the most important questions is how genetic manipulation affects the "behavior" of nerve cells. We are primarily interested in establishing a connection between molecule and behavior: Which molecular and cellular bases synchronize network activity?

Electrophysiological measurements on individual sensory nerve cells led some scientists to conclude that objects of the environment in the brain are represented by the activity of individual nerve cells ("single neuron coding"). Theoretical considerations and empirical data led other scientists to propose the "ensemble coding" model. The neural activity of a group of nerve cells (an "ensemble") represents an object; the activity of a single nerve cell is only a carrier of partial information. Such a model offers more stability, but above all more flexibility: A certain neuron can participate in different nerve cell associations and thus becomes part of various representations.

The population coding model raises the question of how the membership of a neuron in a particular nerve cell cluster is marked. How is a uniform perception created? How are different features of an object bound together to form a coherent whole? The "temporal coding" model assumes that uniform, coherent representations always arise when many nerve cells, which have been excited by different features of an object, "fire" at the same time, ie are active at the same time. In this model, it is not only important that a cell is firing - it is equally important which other cells the nerve cell is firing with at the same time. Our group is interested in the molecular and cellular mechanisms that determine and modulate this synchronous activity of neuronal nerve cell assemblies. Here, too, computer network models are the basis of our hypotheses, which we then check in biological systems.

Using the example of smell, it can be illustrated very well how genetic programs determine perception. On the one hand, the diversity of the odor receptors in the nose is genetically determined, which largely explains the species differences in odor perception. The olfactory receptors sit on the surface of the olfactory cells, which are located in the nasal mucous membrane. Depending on the species, there are several hundred to several thousand different odor receptors that are products of just as many genes. In vertebrates, the odor receptors form the largest family of channel proteins; In humans, the genes for odor receptors make up three percent of the human genome. A special feature of the olfactory receptors is that a olfactory sensory cell only generates one type of olfactory receptor and can therefore only be activated by certain smells.

At this first stage of olfactory perception, population coding means that a scent activates not one, but many hundreds of sensory cells. How many sensory cells are stimulated depends on the complexity of the scent. Only the simplest scents only activate olfactory cells of one type, i.e. olfactory cells with the same type of olfactory receptors on their surfaces. Most scents, however, are complex and activate various olfactory receptors. The advantage of population coding over coding individual nerve cells can easily be seen in the example of smell: The number of odor representations is not limited to the number of genes for olfactory receptors, but is increased many times over by numerous combinatorial possibilities.

It is also genetically determined how the nerve cells of the nasal mucous membrane are connected to the downstream cells in the "Bulbus olfactorius", the olfactory bulb. The processes (axons) of the olfactory sense cells pass on the excitation that was triggered by a scent and transfer it to the processes (dendrites) of downstream mitral cells. The transmission of stimuli takes place in structures that are anatomically easy to recognize. These are the so-called glomeruli. All of the processes of olfactory sensory cells that carry the same olfactory receptors end in them. In experiments with mice it could be shown that the extensions of olfactory sensory cells, the receptor type of which has been modified by genetic engineering, end in another glomerulus. This means: It is genetically determined which downstream nerve cells are stimulated when a fragrance is presented.

Methods that allow the activity of many nerve cells to be measured at the same time have shown that scents can be clearly assigned to neuronal activity patterns. When smelling, this spatial coding ("spatial coding") is of great importance. It is not an exaggeration to say that the structural and functional conditions of the olfactory brain determine which reality is represented in the brain. "Temporal coding" plays an equally important role in olfactory perception: the synchronous activity of nerve cells in the millisecond range is one way in which the membership of cells in a nerve cell cluster can be marked. Electrophysiological methods can be used to measure which cells are active at the same time.

As already explained, genetic programs ensure that sensory cells that are stimulated by the same scent pass on the scent information via their axons, which end in specialized structures, the glomeruli. This principle of interconnection, the bundling of axons in the glomerulus and convergence on downstream cells ensures that the stimulus threshold that is necessary to activate a downstream cell can be reached more easily. From genetically determined peculiarities of the olfactory bulb, one can conclude that mitral cells that are next to each other are very likely to fire synchronously, i.e. are active at the same time. Electrophysiological measurements confirm this - but the mitral cells only fire synchronously if their dendrite tree is in the same glomerulus. This raises the question of the identity of the molecules on which the synchronous activity is based.

We were able to show that mitral cells are equipped with certain channels that enable a rapid flow of information between neighboring mitral cells. These are so-called "gap junctions" - communication channels - which connect the dendrites of mitral cells with one another. However, only mitral cells whose dendrites are located within a glomerulus are linked via gap junctions. This type of neural communication is unusual in the adult brain. Nerve cells mainly communicate via chemical messenger substances that are released at the synapses. In recent years, we have been able to show that neural communication with the help of gap junctions - contrary to what was previously assumed - also exists in the adult brain in certain cell populations. We were also able to prove that synchronous activity in nerve cells that are coupled by gap junctions is easier to trigger and maintain. Genetic manipulations make it possible to specifically switch off gap junctions, which has an effect on the synchronous activity and thus on the "temporal coding": When stimulated, the activity of mitral cells of genetically unchanged mice is synchronous, but not in mitral cells of mice in which the gap junctions have been turned off.

The consequences of these observations on the behavioral level have yet to be tested. We assume that olfactory perception - for example, how to differentiate between complex scents - changes in genetically modified mice. "Temporal coding" is also not specific for the olfactory brain, but is subject to additional other sensory perceptions such as sight and hearing as well as cognitive processes.

In order to determine the molecular determinants of synchronous network activity, it is also important to know where certain channels are located. The individual properties and the "fire behavior" of a mitral cell determine numerous channels, and the synchronous fire behavior of two cells depends crucially on the gap junctions. For modeling studies it is important to know exactly where the communication takes place via the gap junctions: Do gap junctions connect the cell bodies of two neighboring cells or do they connect their processes, the dendrites? And when they connect the processes, are they located proximally - close to the cell body - or distal, i.e. further away from the cell body?

The classic way to localize proteins with antibodies. They "recognize" a certain protein and mark it. However, such studies can only be carried out on fixed - on dead - tissue. Newer techniques make it possible to use so-called in-vivo markers. These are fluorescent proteins that can be made visible in the living cell and even in the living organism. Fluorescent proteins can also be used to mark gap junctions and to track the routes in which proteins are transported in the living cell from the place of their origin to their destination. The transport processes of proteins are also determined by genetic programs, but they are also dependent on epigenetic factors. In genetically modified mice whose gap junctions have been marked, it is possible to examine not only where the communication channels are located in a nerve cell, but also whether they change depending on activity, for example through learning.

Using molecular biological techniques, we have recently succeeded in marking newly formed nerve cells in the adult brain with fluorescent proteins and in following their path. These cells migrate long distances from their place of origin (the subventricular zone) to their destination, the olfactory bulb. But they also migrate to other regions of the brain, such as the cerebral cortex or the hippocampus. Making these newly formed nerve cells visible in the unfixed tissue will make it easier to answer many unanswered questions. For example, we still know little about neighboring cells, which apparently serve as "guides" for the newly created nerve cells in the adult brain, or about processes inside the cells that are decisive for the targeted movement of the new cells. It is also not known how new nerve cells are incorporated into the established network of the olfactory bulb and whether this integration is important for plasticity, the ability to learn and adaptation.

In the last few years we have mainly tried to clarify which cells in the brain are capable of generating and coordinating synchronous network activities in certain frequencies and which central molecules / proteins play a role in this. Our investigations were initially carried out on brain structures such as the hippocampus or the cortex. Later we included the olfactory bulb in order to be able to track genetic changes from the molecular to the behavioral level. The spatial and temporal coding, which was described using the olfactory bulb as an example, is more or less similar for other sensory perceptions. The further interconnection is specific for the olfactory system. For all other senses, the information reaches the cortex via an interconnection in the thalamus, a part of the diencephalon. Only in the olfactory system is there, in addition to this usual thalamo-cortical projection, a direct flow of information that leads from the olfactory bulb to the limbic system, i.e. to those brain structures that are responsible for emotions, motivation and certain forms of memory. So there is clearly an anatomical basis for the statement of the English writer Rudyard Kipling, who writes in his poem "Lichtenberg": "Smells are surer than sounds and lights to make your heart-strings crack".

Not least because of such connections, it was always important for me to pay attention to how the object and topic of my research was examined by humanities scholars, especially since I agree with the Argentine writer Jorge Luis Borges that great poets are not inventors, but - like natural scientists - Are explorers. When it comes to brain performance and brain functions, too, it is ultimately about recognizing the truth / reality in its complex relationship to the physical outside world, to neural activity and the subjective world of experience. This relationship is not linear and constant: the perception of an object does not result in the activity of the same nerve cells every time. Experience, expectations and emotions, the motivation or the state of alertness of the perceiver influence which cells are activated. The current subjective state of mind will also have a decisive influence on how a stimulus is perceived. It is therefore not possible to transfer the characteristics of an object one-to-one into the constant activity pattern of a neural ensemble.

"This is the breath of nature"

The "lower" sense of human beings - and how writers view smell

Understanding the performance of the brain in a strictly scientific sense as well as in its cultural performance such as music, philosophy and literature, especially where these strive to reflect on objective and subjective perception, is an important concern of my scientific work. If one stays with the example of the olfactory system and examines the literature of the 20th century, it is noticeable that brain researchers have succeeded in better understanding what happens when a scent is mapped in the brain on a molecular and cellular level. The artist, on the other hand, is more concerned with the relationship between the object (here smell) and the subjective world of experience.

It is interesting to see how the sense of smell is treated in literature, also because its place in 20th century literature has undergone an interesting change.

The sense of smell has been one of the so-called lower senses since ancient times.Plato and Aristotle contrasted the lower senses of smell and taste with the "higher" senses of sight and hearing. Even the ancient philosophers dealt extensively with the question of how the five senses function in perceptual processes. You are also already looking at the role the senses play in recognizing the truth. While sight and hearing are assigned an important function in cognitive processes, the sense of smell and taste are not only viewed as unimportant, but almost as a hindrance, since they counteract physical transcendence. According to Plato and Aristotle, the "lower" senses are not suitable for gaining knowledge because, unlike seeing and hearing, they do not function at a distance, but require direct contact between object and body. Despite different positions, which cannot be discussed here, Plato and Aristotle agree that only seeing and hearing are beneficial to the "philosophical senses" and the intellect. This elevation of seeing and hearing above the other senses must be understood against the background of the philosophical views of the two philosophers. In the opposing pairs of mind-body, mind-feeling, culture-nature and man-woman (with Aristotle), the higher value is assigned to the former.

The hierarchy of the senses has remained unchanged over the centuries. Differences in the importance attached to the sense of smell and taste must be considered on the basis of the overall philosophical concept of the respective humanities.

Numerous statements on the function of the senses can be found primarily in philosophical writings on aesthetics, which developed into a philosophical discipline of its own in the 18th century. For Kant, smell is inferior to all other senses. Like Plato and Aristotle, Kant also finds that the dependence of physical well-being on the lower senses makes them unsuitable for cognitive knowledge and aesthetic judgments. For Hegel, too, only the "theoretical" senses of seeing and hearing are suitable for judging an art object. The direct physical reference of the "practical" senses, on the other hand, makes an objective judgment about a work of art impossible.

The thematization of the sense of smell in fine literature takes place in connection with situations that lie beyond scientific-empirical analysis. The interest of the respective writers in the "lower" senses is very different - but from most works it can be seen that they are by no means as low as we know from philosophical writings. This may have something to do with this particular form of art: writers have always been interested in the sensual, irrational and emotional. For writers, smell and taste are therefore excellent triggers for conditions that allow us to look into the subjective state of mind and the psychological life of the heroes of the novel.

The relative and subjectivity of olfactory perception is emphasized in the story "Die Betrogene" by Thomas Mann. The aging protagonist Rosalie is confronted with her daughter Anna. The two women embody two extremes of female life forms: the mother "sociable by disposition", of cheerful disposition, the daughter rational, "of unusual intelligence". The difference between the two women manifests itself most clearly in their attitude towards their own body, towards femininity and towards nature. Given the opposing attitude towards femininity of both women - a central theme of the story - the opposing attitude towards nature is not surprising. Rosalie is a "nature lover", but it is said of the daughter that she is "not on the best of terms with nature, but has to transfer it into the spiritual". The perception of nature and its effect on the protagonists takes place primarily through the sense of smell. Thomas Mann impressively describes how the two women react in opposite ways to a complex mixture of fragrances in nature: "Rosalie did not use fabricated odoriferous substances or perfumes (...) But what nature attributes to our olfactory sensorium as holdiness, sweetness, spicy bitterness, also in sultry, intoxicating things has to offer, she loved that and accepted it deeply and gratefully, with the most sensual devotion. On one of her walks there was a slope, an elongated fold in the ground and a shallow gorge, at the bottom of which was deeply overgrown with jasmine and buckthorn bushes, from which it was damp -warm, thunderstorm-prone June days, whole swaths, clouds of warmed fragrance billowed up almost deafening "Child, how wonderful! That is the breath of nature, that is it, her sweet breath of life, heated to the sun and soaked with moisture, like that." it blows blissfully to us from her lap. Let us enjoy him with admiration, who are also her dear children. "It is said of Anna that these scents gave her a headache, she pulls her mother on, and in response to the enthusiastic, delighted utterances of Rosalie, she replies," I like her (the Nature) less and causes this pressure in my temples with their scented brew. "

One of the first pictures in the novel "The Leopard" by Tomasi di Lampedusa, which describes a walk of the prince in his garden, is magnificent and symbolic. It is a garden that appeals not to the eye but to the sense of smell, a "garden for the blind", as it is called in the novel. The prince is described as "driven, here by the pride and intellectualism of the mother, there by the sensuality of the father". It is the latter that makes the prince, a patriarch and a symbol of masculinity, receptive to the beautiful, the emotional and the sensual. At several points in the novel, a fragrance evokes memories in the protagonist, all of which are sensual and related to the prince's sexual desires. The "dense, almost shameless" scent of the roses in his garden reminds him of the thighs of a dancer. On the night drive to Palermo, the smell of the blooming orange gardens is associated with "Huris and sensual orgies after death". It is not without concern that the purpose of this trip is a marital fling and was dictated by the "thorn in his flesh that urged him to revolt against the coercion and pressure". And last but not least, the famous ball scene and the dance of the no longer young prince with the enchanting Angelika should be mentioned. It is the smell of her perfume, but above all that of her young, smooth skin, that makes the prince think of the sentence: "Your bed sheets must have the scent of paradise."

Both literary examples show that in literature there is no clear categorization of the senses as "high" and "low", or "male" and "female". In the story "Die Betrogene", seeing and smelling are associated with the preferential sense of perception of two women, who admittedly embody the rational or emotional type of woman. The union of "male" and "female", of "seeing" and "smelling" is even more complex in the form of the same person, the prince in the "leopard". It is not uninteresting that the prince inherited the "male" character traits from the mother and the "female" traits from the father.

In Joris-Karl Huysman's novel, "Against the grain", we find that smells are also suitable as building materials for creative work. A long chapter deals with smelling. The hero Des Esseintes lives cut off from the world in a house that stimulates all the senses. The aim of this aesthetic decadence is to increase perception and to evoke new, unimagined sensory experiences. In addition to a taste organ, Des Esseintes also creates scent landscapes. For example, he combines scents to evoke certain images from memory, but in this way creates new landscapes and images. Des Esseintes competes with nature and is the creator of imagined scented landscapes. The excess of Des Esseintes' creative process in the design of his scent images becomes clear in the fainting attacks with which the act of creation often ends.

Where else but in the great novel of the century "In search of lost time" by Marcel Proust, the so-called lower senses experience the rehabilitation they actually deserve: a piece of biscuit dipped in tea brings up memories of childhood and youth in the narrator. It is the "lower" senses that inadvertently conjure up memories. The high value assigned to sensual experiences is related to Proust's interest in the inner reality of his protagonists. With the thought that intuition, dream and suffering rather than reason make access to reality possible, Proust ties in with the romantic tradition. According to Proust, smell and taste are the initiators of memories that enable access to inner reality. It is the inner reality and not the physical outer world that surrounds us that, according to Proust, is decisive for the creation of a work of art. Since Proust ascribes the highest reality to art, smell and taste are the initiators of processes that are linked via memory with cognition at the highest level - creative work.

Examples on this topic from the field of the visual arts are rare. The allegorical representation of the smell in the six-part tapestry series "The Lady with the Unicorn" is all the more impressive. In addition to the craftsmanship, the multiple interpretations that allow a connection between the personal, socio-political and religious levels are particularly impressive. Furthermore, it is noticeable that the five senses - unlike in philosophical texts - appear as equal in this representation: They are equal instruments of perception and at the same time are obstacles on the way to a higher spiritual, intellectual, religious truth.

Especially at a time when scientific knowledge is experiencing rapid progress, it seems important to me not to ignore the humanities perspectives and interpretations.

Prof. Dr. Hannah Monyer
Interdisciplinary center for neuroscience
Im Neuenheimer Feld 364, 69120 Heidelberg
Telephone (0 62 21) 56 24 01
E-mail: [email protected] , [email protected]