Happiness, in one form or another, seems to be a common goal, which each of us would like to achieve. We often behave as if we can find a way to complete satisfaction - comfort, saturation, warmth, some other reward - and be happy all the time just by making some right choices. But the pleasure of even the most pleasant sensations is transient, and this leads to the appearance of boredom and the desire to try something new and amazing. I, as a neuroscientist, cannot help but think about whether the glibness of our satisfaction is inevitable, or is it a certain feature of the brain that, having understood that, you can learn how to deal with it.
Many everyday functions of the brain seem so natural that we can hardly distance ourselves from them to look at them from the side. The brain is committed to noticing things. Obviously, the main work of the brain is perception; based on the perceived, he can make assessments, and based on them - to act. This work is performed by the neurons of the nervous system. They find and submit input data to the external (and internal) world, analyze the data, and respond to this analysis with an appropriate action. The action is usually understood as movement: the neurons send signals that cause the muscles to contract, which allows you to perform some actions. The input data comes from the senses, the analysis is often called associative, and the output is motility. Trinity of feelings / associative analysis / motility is a neural analogue of perception / assessment / action.
How do the neurons that make up the brain cope with the detection and analysis of what is happening in the outside world? The simplest answer is that they primarily rely on the information translation service. The parts of the body that we consider sensory organs - the eyes, ears, nose, tongue, skin - contain receptor cells that perceive information. On the membranes of these cells are tiny protein molecules; they translate (technically speaking) the physical effects of the external world - light, sound, chemicals, heat - into electrical signals,
action potentials that form the language of the brain. Transmitting proteins form a small path, an
ion channel through which charged particles, such as sodium or potassium, enter or exit the cell. The movement of ions generates electrical signals. Each signal spreads along the entire length of the cell due to other proteins - also forming ion channels - which results in the release of a chemical
neurotransmitter . The next neuron receives a neurotransmitter due to other receptor proteins, which are also ion channels or are connected to ion channels. Our ability to notice mainly depends on our protein-ion channels.
Interestingly, almost all of these proteins respond to changes in stimuli; but in the presence of prolonged and constant stimulation with a soft to moderate intensity, many of them turn off and prevent ions from passing through them. We call this process adaptation (or desensitization, or inactivation, depending on the physical basis). It leads to the appearance of familiar sensations. Due to adaptation, when moving from a place with bright lighting to an unlit room, at first it seems dark, and after a while the lighting in it already seems normal. Only when you go back to the sun do you realize how dark it was in the room — or how bright it is now. Similarly, most people adapt to the smell of food soon after they enter a restaurant, or to the coolness of a pool after jumping into it on a hot day, or to the background noise of a refrigerator. After a short exposure, odor, cold or noise - if they are not strong enough to cause inconvenience - is no longer felt, and we do not pay attention to them. That is, as they say, we get used to them. In particular, due to adaptive ion channels, we feel a lot not in absolute value, but in contrast to what was previously (though not all types of adaptation occur due to ion channels, and not all feelings are subject to adaptation). In one exceptional case, experimenters managed to demonstrate this phenomenon by stabilizing the image on the retina. Our eyes usually make small sharp movements,
microsaccades , which allows retinal cells to compare light reflected from dark and light areas of any visual environment. By tracking human eye movements and changing the image projected on them, neuroscientists were able to show that when a picture is artificially fixed on the retina, it seems to the person that it disappears [Ditchburn, RW & Ginsborg, BL Vision with a stabilized retinal image. Nature 170, 36-37 (1952) .; Martinez-Conde, S., Macknic, SL, Troncoso, XG, & Dyar, TA Microsaccades counteract visual fading during fixation. Neuron, 49, 297-305 (2006)]. If you cannot compare, the world becomes gray. In other words, diversity does not just add to the taste of life; in principle, you can only see something through change.
This sensitivity to change and insensitivity to permanence does not stop at the level of sensory receptors. Deeper in the brain, in almost all neurons, there are other protein-ion channels — in particular, sodium channels that trigger action potentials (by passing sodium ions into the neuron), and potassium channels that stop action potentials (by releasing potassium ions from the neuron). Sodium and potassium channels are different, and many of them are also inactivated — turned off — during use. Consequently, even when chemical neurotransmitters provide long-lasting or repetitive stimuli to neurons, the internal properties of ion channels limit the number of action potentials. For example, in some neurons, inactivation of sodium channels makes it increasingly difficult to generate action potentials with constant stimulation.
But in some neurons, certain sodium channels prevent inactivation with a special protein that blocks it. Such neurons gladly launch long high-frequency sequences of action potentials. Many such neurons are found in the cerebellum and brain stem. [Lewis, AH & Raman, IM Resurgent current of voltage-gated Na + channels. Journal of Physiology 592, 4825–4838 (2014)]
In the meantime, certain potassium channels gradually increase the flow of ions, helping to slow down or turn off signals from neurons after passing several action potentials. The interaction between the flows of sodium and potassium ions allows you to generate electrical signals only at the beginning of the stimulus - this process is called accommodation. And although there are exceptions, most of the major excitatory cells of the cortex and hippocampus — those that encourage action potentials in target neurons — are subject to accommodation.
In some cells, accommodation can be reversed by neurotransmitters, such as
norepinephrine . Interestingly, the global effect of norepinephrine on the brain is to increase attention. Many toxins and poisons, such as those of scorpions and snakes, prevent inactivation of sodium channels and block potassium channels, which leads to convulsions and death - that is, the brain can suffer from too much good. [Madison, DV & Nicoll, RA, Actions of noradrenaline, recorded intracellularly in hippocampal CA1 pyramidal neurones, in vitro. Journal of Physiology 372, 221–244 (1986); Hille, B. A K + channel worthy of attention. Science 273, 1677 (1996)]
We don’t always understand what information the accommodating neurons carry, but we know that they react most strongly to changes in the stimulus. It is hard not to succumb to the temptation to conclude that the more activity in the brain, the better - but it is very good that some neurons have the ability to turn off their signals through the inactivation of ion channels. Many neurological diseases are associated with an excess of action potentials in neurons, which usually respond quite a bit. Such “over-irritability” is often found with pain or epilepsy. When the first is too many feelings, with the second - muscle contractions. Often the best drugs for such cases are those that inactivate sodium channels. Even people without such syndromes are familiar with the analgesic effect of blocking sodium channels of drugs like
novocaine or
lidocaine . Drugs for epilepsy do not turn off the nervous activity at all, but limit hyperactive neurons.
Similarly, the receptor proteins of neurotransmitters may experience desensitization, in which their ion channels are turned off during prolonged exposure to stimuli. They can be switched off due to desensitization, which is an intrinsic property of the protein, or because of the short life of the neurotransmitter itself, because it is destroyed by enzymes or it is absorbed into adjacent
glial cells . Substances that affect these processes and prolong the action of neurotransmitters can drastically change the work of the nervous system. Tranquilizers prolong the duration of the flow of ions through the channels opened by the neurotransmitter GABA. Nerve paralytic gas prolongs the action of
acetylcholine , a neurotransmitter that causes muscles to contract.
But neurons have an interesting ability to respond to a long-term increase in the effects of neurotransmitters — at intervals of several days or more, which can lead to an excessive number of signals passing through a particular nerve circuit — they simply absorb their own neurotransmitter receptors, and fewer working receptors remain on the cell surface. . Such a reaction may underlie the emergence of resistance to drugs, drugs and spicy foods.
The discovery of spicy foods does not occur in the receptors of neurotransmitters in the brain, but in peripheral chemical receptors that respond to
capsaicin , a natural substance that makes spicy pepper. An interesting example of addiction is capsaicin-based ointment, which desensitizes receptors and relieves pain in arthritis and neuropathy.
Conversely, with a decrease in the production of neurotransmitters, a certain neuron can produce more receptor proteins and associated ion channels. In this way, hyperstimulation returns to normal perception, and lack of stimulation adjusts the nerve circuit to an increased sensitivity even to weak signals. How do cells know this? Through various feedback systems, many of which use special biochemical properties of calcium ions, allowing a neuron to find, so to speak, a comfortable or suitable middle ground. Such processes can be triggered when the stimulation, initially pleasant - or repulsive - is repeated over and over. Acute perception subsides when the brain finds its reference point.
This process is called
homeostasis , and a lot of effort is spent on studying the “homestatic plasticity” of the neural circuits — the return by the neurons of the basic control point even with changes in the strength of the input stimulus. [Turrigiano, G. Homeostatic synaptic plasticity: local mechanisms for stabilizing neuronal function. Cold Spring Harbor Perspectives in Biology 4, a005736 (2012)]
At the level of the whole organism, the sensations from these stimuli change accordingly; decrease in the case of repeated stimuli, and then restored in the event of a change. A simple demonstration of this phenomenon can be experience with marine clam
aplicia , which, in response to a light touch, first engages the gills. After a series of harmless touches, he becomes accustomed and stops responding, until the touch is combined with something unpleasant, such as electric shock. When habituated, the receptors do not experience desensitization - instead, the neurotransmitter ends in neurons. [Kandel, ER & Schwartz, JH Molecular biology: Modulation of transmitter release. Science 218, 433–443 (1982)]
In the case of more pleasant sensations, hungry rats will work for food, whether it is ordinary or especially tasty, and saturated rats will work only to get sweets that they especially like. The motivation of rats to work for food can be reduced with the help of drugs that interfere with the work of the receptors of natural opiates and dopamine - neurotransmitters of nerve circuits that signal rewards. It turns out that the contours of reward are stimulated by both anticipation and absorption of food, but in saturated rats this happens only if the food benefits compared with recent experience. [Barbano, MF & Cador, M. Opioids for the hedonic experience. Psychopharmacology 191, 497–506 (2007)] In other words, do not leave room for dessert; it will still be pleasant as long as it tastes better than what came before it.
Familiar stimuli and the sensations they create can also cause the appearance of other modifications of the ion channels and receptors of neurotransmitters that can change the entire neural circuits. In fact, some brain contours of many animals (including us) are so well able to predict the result of a well-known stimulus that they send back signals that balance the sensation of what is happening. The body does not even notice that something is happening - until something different or unexpected happens.
An interesting illustration of the brain's ability to overlook the known is electric fish, whose electrical sense allows them to sense electric fields. They study the environment with the help of an electric organ discharge (REO) - a special “scream” that creates an electric field around the fish. In the presence of objects, this field is distorted - perhaps it is a bit like distortion of the skin shape when touching the object. It is the deviation from the usual form that suggests the need to save or explore. The constant REO signals themselves are not important. Neurons that create REOs also send a signal to the fish’s brain, indicating that they have worked. This signal is strictly opposite to the sensory signal received by the fish as a result of feeling its own undistorted field, obtained as a result of REO, as a result of which it neutralizes the feeling of the fish of its own "cry" when there is nothing nearby. [Bell, C., Bodznick, D., Montgomery, J. Bastian, J. cerebralum-like structures. Brain Behavior and Evolution 50, 17–31 (1997)]
Being able to get used to and ignore incoming information, which is static, familiar, predictable and safe, helps in terms of behavior. In other words, it has an evolutionary advantage. If we constantly felt the touch of clothes on the skin or the slight smell of fabric softener, it would be distracting, to put it mildly, and could even prevent us from detecting and reacting to a significant signal — a slap on the shoulder or the smell of burning toast. The inability to predict and adapt is perhaps one of the factors contributing to the development
of autism spectrum disorders . [Gomot M. & Wicker, B. A challenging, unpredictable spectrum disorder. International Journal of Psychophysiology 83, 240–247 (2012)]
In addition, signals that communicate information already known to the brain would be an unnecessary waste. All these ions, moving in and out of cells to send signals in the brain, cannot simply remain from the side opposite to the one from which they moved. Energy is literally spent on pumping out sodium back from neurons and pumping potassium back into it, so it’s more effective not to create action potentials that do not carry the information that is worth it.
Does this mean that only something new makes sense, and that everything familiar must be discarded as soon as the sensations become boring? On the contrary; I think that this is the key to happiness, compatible with the principles of the brain. The ability to detect even familiar stimuli is restored by a quick “reset”, allowing one to recover from desensitization enough to enhance subsequent sensations. It seems to me that it is the ability of the brain to perceive sensations in contrast that may partly explain why our attempts to achieve eternal satisfaction remain unsuccessful. The brain works on a curve, constantly comparing the current situation with the previous one, and therefore misfortune can be the secret of happiness. Not an absolute misfortune, of course, but a short-term cooling, which allows us to feel warmth, the feeling of hunger, which makes satiety so desirable, a period of despair, sending us into a tremendous feeling of triumph. The path to satisfaction passes through contrasts.
Indira M. Raman - Professor of Neuroscience at Northwestern University