Physiology of analyzers - higher nervous system activity
Topic: « Physiology of analyzers and higher nervous activity »
Purpose: to disassemble process of perception and transformation mechanical, chemical. Electromagnetic, thermal kinds of energy in a nervous signal and mechanisms ligand– receptorinteractions; to consider classification and properties of receptors.
Reception name process of perception and transformation of mechanical, thermal, electromagnetic and chemical energy in a nervous signal or complex sequence membrane and цитоплазматических processes. Function reception specially sensitive formations conditionally divided on features of their organization, character and mechanisms of interaction with a signal on carry out greater groups – cellular (molecular) and touch receptors.
CELLULAR RECEPTION
Information interchange between cells occurs to participation of biologically active substances, including hormones, mediators, oligopeptides, etc. the Obligatory stage of this interaction linkage of molecules of the substances named ligandми, with cellular receptors corresponding{meeting} them is. The role of cellular receptors is played with the albuminous molecules, capable “to learn specific to them ligands. They can be built in a cellular membrane (receptors to insulin, peptides, mediators) or to be inside of a cell- in cytoplasm and a kernel (receptors of steroid hormones).
As membran, and endocellular molecular receptors have the active centers of linkage providing their specific interaction with ligand. After linkage with ligand the receptor transfers{transmits} a signal to executive systems: opens or closes ionic channels, activates specific enzymes or operates{works} itself as ионофора.
Ligand-receptors interactions proceed in two stages. At the first stage as a result conformational changes receptor fiber the complex ligand with a molecule of a receptor on a membrane is formed; on the second – the signal from this complex is transmitted to internal structures of a cell both with participation of the receptor, and without it{him} – due to cytoplasmic secondary intermediaries, « started Ligand-receptors interaction on a membrane.
MECHANISMS LIGAND-RETSEPTORNOGO OF INTERACTION
The Starting stage in realization ligand-receptor interactions is, as it was already mentioned, linkage ligand with receptors effector cells and the subsequent internalization of this complex. Receptors for substances albuminous and пептидной the nature are located on an external surface of cellular membranes; receptors стероидов and derivatives тирозина – in cytoplasm and a kernel of a cell. According to it allocate two kinds ligand-receptor interactions – Membrane and Nuclear (cytoplasmic).
Membranereception. Substances, insoluble in lipid bilaryerscellular membranes, are not capable to get into a cellindependently therefore are compelled “to use” system of secondary intermediaries. Interaction of a molecule ligand with Membrane a receptor initiates (“starts”) the cascade enzymaticreactions which essence is in brief reduced to the following:
– The information on interaction a ligand-receptor is transferred{transmitted} to enzyme – membrane adenylate cyclase;
– adenylate cyclase it is activated and, actions on ATP membranes, stimulates formation from it cyclic adenosine monophosphate (cAMP). Last is the universal endocellular intermediary of realization of interaction with a cellof chemical substances;
– cAMP stimulates endocellular fermental systems, activates a gene of a cell, promoting synthesis of specific cellular fibers.
Nuclear reception
Nuclear reception - Substances, soluble in lipid bilayerscellular membranes, freely pass through it. In cytoplasm they incorporate with specific receptor fibers and only after that form a complex a ligandreceptor. After of some transformations this complex gets into a kernel where action of a hormone is realized at a genetic level.
Membranereception.
The Majority protein-peptide hormones cooperates with the certain receptors on lateral aspect of a cellular membrane, from above 100 from which are integrated to G-fibers of a plasmatic membrane. The majority of them has 7-domain structure.
Apparently from figure, полипептидная the circuit of a receptor including from 400 up to 600 аминокислотных of rests, 7 times “stitches” a plasmatic membrane. The domain with NH2-kohhom is outside, with the ß««¡-END – inside of a cell. The site of interaction with G-fibers is in the third цитоплазматической to a loop.
G-fibers are obligatory participants of transformation of a hormonal signal.
Tens receptors are integrated to different G-fibers, but also the same G-fiber can be integrated to many receptors. G-fibers or participate in formation of the second intermediaries, or directly carry out regulatory functions in a cell. G-fibers operate several мембраннымиenzymes and a beside of ionic channels, cooperate with cytoskeleton.
Through 7-domain receptors many hormones work: liberiny and statins hypothalamus, adrenaline, angiotensin-¡, dopamine, serotonin, histamine, the some people growth factors, partially eicosanoids.
The Hormones connected with 7-domain receptors, never get into a kernel and influence a metabolism of a cellby means of the complex biochemical mechanism which leads to biological effect with participation of the second intermediaries.
Cells Formed on a surface hormone – receptor complexes carry out many functions: activate electrodependent and a receptor-operated ionic channels, adjust{regulate} activity of G-fibers, change an exchange nucleotides and phosphoinositides, concentration of the ionized calcium in cytoplasm. Formation of the second intermediaries of hormonal reactions in cells{cages} is as a result facilitated or oppressed.
The Biological effect of the hormones cooperating with membrane receptors is carried out with participation of the second intermediaries.
The Second intermediaries
The calcium mechanism
The calcium mechanism - The elementary endocellular intermediary – an ion of calcium; it is known more than thirty hormones operating with its participation.
Cells Formed on a surface hormone receptor complexes activate кальциевыеchannels and raise{increase} its{his} maintenance{contents} in cytoplasm due to the strengthened receipt extracellular Са2 + and liberation Са2 + from endocellular depots.
Biological action Са2 + is provided:
- Change of permeability of a cellular membrane for ions;
- Activation of enzymes;
- Interaction with endocellular секреторным the device.
As a result of increase of concentration Са2 + electromechanical interface and muscular reduction is realized, from the nervous terminations by exocytosis is allocated НСЙрОМедиатор, etc.
Activated by calcium кальмодулин operates{works} with different ways: stimulates formationof other second intermediaries, мембранныхenzymes or fibers цитоскелета or activates directly Са2 +-dependent протеинкиназы, causing фосфорилирование existing in a cellbefore the synthesized fibers-enzymes. In turn active enzymes cause final physiological reactions.
Calcium-polyphosphoinositide mechanism. Accumulation of Ca2 +, the second intermediary carrying out function, can be caused by other second intermediaries – diacylglyceroland inositol triphosphate which are used by a cellfor long activation of protein kinases.
Liberation Са2 + from endocellular depots under action метаболитов фосфолипидов, containing инозитол, occurs{happens} as a result of linkage of these secondary intermediaries to specific receptors on internal cellular membranes.
At presence метаболитов инозитолов Са2 + makes active протеинки–назу With which фосфорилирует fibers, and those cause final physiological effects.
The Guanilatmonofosfatny mechanism. One of the endocellular connections influencing on кальциевыйan exchange, is cGMP, synthesized guanylate cyclase. Activity guanylate cyclase increases under influence NO- monoxide of nitrogen which is synthesized in cells{cages} from amino acid arginine.
The Stimulator of synthesis cGMP is, for example, предсердный on a hormone. The receptor of this hormone through penetrates a plasmatic membrane and in the цитозольной the domain possessing guanylate cyclaseйactivity has parts.
Adenylate cyclase mechanism. In a plasmatic membrane there is an enzyme adenylyl cyclase catalyzes transformation ATP in cAMP. Accumulation cAMP in a cellis determined by interaction of a гормонрецеп-even complex with мембраннымиG-fibers which can stimulate or suppress its activity and thus adjust{regulate} action of hormones on a cell.
As a result of the complex mechanism of interaction of a hormone, a receptor, G-fibers and adenylate cyclase in a cellthere is disintegration ATP and formation {education} from moleculesof ATP cAMP. When the maintenance {contents} of cAMP in a cellincreases, action of a hormone amplifies, as there is an activation μá ¼ õ-dependent protein kinases.
On an educational level цАМФ the initial hormonal signal amplifies in 102 times; at a level of activation µá¼õ-dependent protein kinases in 104; effects протеинкиназ in cascade multiply a hormonal signal up to 108.
Interaction of the second intermediaries
Cytoplasmic RECEPTION
Steroid hormones and derivatives тирозинаcooperate with ци–топлазматическимиreceptors then get into a kernel of a cell.
RECEPTION steroid hormones
RECEPTION steroid hormones - Are known цитоплазматические receptors to эстрадиолу, андрогенам, to glucocorticoids and I mineralocorticoid -shall give, which structural organization for different steroid hormones is identical.
Steroids act in a kernel of reacting cells {cages} in a complex with cyto-cindery receptors. Suchgormon receptor complexes before to reach {achieve} a kernel, undergo conformational changes in the cytosol, and after removal {distance} from them low-molecular substances special transport fiber transfers {carries} them to a kernel. Transition steroids in a kernel causes structural reorganization of chromatin and activation of genes in corresponding {meeting} places. Steroidretseptornyecomplexes are capable to communicate practically with all components of chromatin, from DNA, RNA, some sour and basic fibers. A number {line} of effects of steroids is carried out outside of a kernel, on the posttranscriptionala level as a result of interaction with receptors of ribosomes, with plasmatic membranes of components of the cytoskeleton.
Alongside with it there are data, that стероидны in the beginning communicate specific fibers of membranes of a cellwhich transport them or to cytoplasmic to a receptor, or, passing it, is direct to receptors of a kernel.
In transmembrane carrying out of hormones and the subsequent endocellular interaction of steroid hormones the certain role is played with G-fibers. Their specific субъединицы connect the certain hormones, and nonspecific can enter cross interactions and adjust{regulate} ways of receipt of these or those hormones to a kernel through different endocellular systems.
In an organism there is no cell which is not testing influences of steroid hormones. Each cellis under action different steroids. In cells of separate bodies and fabrics steroid hormones collect and cooperate in various parities{ratio}, initiating answers of various intensity.
Reception of thyroid hormones. Mechanisms of action of thyroid hormones up to the end are not opened. Triiodothyronine (T3 ) contacts receptors in a kernel of a celland influences on a gene, covering processes of a transcription and translation owing to what stimulates synthesis of fiber in all cells {cages} of an organism.
Action of thyroid hormones is carried out also after complex -financing them with receptors of a cellular membrane where they directly influence activity of some enzymes localized in it {her}, stimulate transport of glucose and amino acids through a membrane.
Gormonretseptornye the complexes formed on a surface of a cell {cage}, get in cytoplasm where complexed with fibers and form endocellular fund (pool) of thyroid hormones.
Endocellular action of thyroid hormones in many respects is defined {determined} by interaction of triiodothyronine (T3 ) with receptors of mitochondria and increase of activity of enzymes – regulators of a carbohydrate exchange.
Thus, there are two mechanisms postmembrane actions of the hormones essentially differing on the basis of where it is formed gormonretseptorny a complex – inside of a cellor on its {her} surface.The Most typical attribute of the hormones operating{working} through system of secondary intermediaries, their ability to cause activation before the synthesized, preexisting fibers – enzymes is, therefore their effects develop rather quickly.
The slowest effects on a cellular metabolism render steroid and thyroid hormones as they realize the action in a cell through expression of genes, with formation of set mRNA, fibers initiating in turn synthesis.
At the same time and peptide hormones also possess ability selectively to influence a transcription of genes in a kernel of a cell. This effect of peptide hormones can be realized from a surface of membranes of cells both due to secondary intermediaries, and by direct receipt of hormones inside of a cell and the mechanism of internalization hormone receptora complex.
Mechanisms of receptor excitation
- A stimulus acting on the receptor cell causes changes in spatial configuration of protein receptor molecules incorporated in the protein-lipid complexes of its membrane.
- This causes changes in membrane permeability to definite ions (most commonly to sodium) and appearance of ion current generating the so-called receptor potential.
- In primary sensory receptors this potential acts on most sensitive parts of the membrane, which generate action potentials or nerve impulses.
- In secondary sensory receptors the receptor potential causes the neuro-transmitter quanta to be released from the presynaptic terminal of the receptor cell.
- A neurotransmitter, e.g. acetylcholine, acts on the postsynaptic membrane of a sensory neuron causing its depolarization (postsynaptic potential, PSP).
- The PSP of the primary sensory neuron is called generator potential which leads to the generation of impulse response.
- The receptor and generator potentials in primary sensory receptors have the properties of a local response and do not differ from each other.
Differences between LR and AP
Local excitation (local response L.R) | Spreading excitation (action potential – AP) |
occurs at subthreshold stimulation | occurs at threshold stimulation |
not mending the law “all or nothing” (law of force) | mending the law “all or nothing” |
does not apply, is capable of damping decrement | propagates without decrement |
gradual dependence on the strength of the stimulus | amplitude and character AP does not depend on the strength of the stimulus |
local responses are summarized | not cumulative |
- Most receptors have the so-called background discharges or impulsation, i.e. they spontaneously release neurotransmitter without any stimulation.
- As a result, information on a signal can be transmitted not only in the form of acceleration, but also in that of deceleration of the flow of impulses.
- At the same time, the presence of these discharges leads to thedetection of signals against the background of ‘noises’, i.e. impulses, unassociated with external stimulation, which arise in receptors and neurons as a result of spontaneous release of neurotransmitter quanta and multiple excitatory interactions between the neurons.
- These ‘noises’ interfere with detection of signals, especially at their low intensity and insignificant changes.
- Therefore, the concept of the reaction threshold acquires a statistical pattern: to decide on its presence or absence the threshold stimulus should be determined several times.
- This is correct both at the level of behavior of an individual neuron or receptor and all the level of the reaction of the whole organism.
Introduction
In order to survive – at least on the species level – we continually need to make decisions:
- “Should I cross the road?”
- “Should I run away from the creature in front of me?”
- “Should I eat the thing in front of me?”
- “Or should I try to mate it?”
To help us to make the right decision, and make that decision quickly, we have developed an elaborate system: a sensory system to notice what’s going on around us; and a nervous system to handle all that information. And this system is big. VERY big! Our nervous system contains about nerve cells (or neurons), and about 10-50 times as many supporting cells. These supporting cells, called gliacells, include oligodendrocytes, Schwann cells, and astrocytes. But do we really need all these cells?
Keep it simple: Unicellular Creatures
The answer is: “No!”, we do not REALLY need that many cells in order to survive. Creatures existing of a single cell can be large, can respond to multiple stimuli, and can also be remarkably smart!
We often think of cells as really small things. But Xenophyophores (see image) are unicellular organisms that are found throughout the world’s oceans and can get as large as 20 centimetres in diameter.
And even with this single cell, those organisms can respond to a number of stimuli. For example look at a creature from the group Paramecium: the paramecium is a group of unicellular ciliate protozoa formerly known as slipper animalcules, from their slipper shape. (The corresponding word in German is Pantoffeltierchen.) Despite the fact that these creatures consist of only one cell, they are able to respond to different environmental stimuli, e.g. to light or to touch.
Physarum Polycephalum
And such unicellular organisms can be amazingly smart: the plasmodium of the slime mould Physarum polycephalumis a large amoebalike cell consisting of a dendritic network of tube-like structures. This single cell creature manages to connect sources finding the shortest connections (Nakagaki et al. 2000), and can even build efficient, robust and optimized network structures that resemble the Tokyo underground system (Tero et al. 2010). In addition, it has somehow developed the ability to read its tracks and tell if its been in a place before or not: this way it can save energy and not forage through locations where effort has already been put (Reid et al. 2012).
On the one hand, the approach used by the paramecium cannot be too bad, as they have been around for a long time. On the other hand, a single cell mechanism cannot be as flexible and as accurate in its responses as a more refined version of creatures, which use a dedicated, specialized system just for the registration of the environment: a Sensory System.
Not so simple: Three-hundred-and-two Neurons
While humans have hundreds of millions of sensory nerve cells, and about nerve cells, other creatures get away with significantly less. A famous one is Caenorhabditis elegans, a nematode with a total of 302 neurons.
C. elegans is one of the simplest organisms with a nervous system, and it was the first multicellular organism to have its genome completely sequenced. (The sequence was published in 1998.) And not only do we know its complete genome, we also know the connectivity between all 302 of its neurons. In fact, the developmental fate of every single somatic cell (959 in the adult hermaphrodite; 1031 in the adult male) has been mapped out. We know, for example, that only 2 of the 302 neurons are responsible for chemotaxis (“movement guided by chemical cues”, i.e. essentially smelling). Nevertheless, there is still a lot of research conducted – also on its smelling – in order to understand how its nervous system works!
General principles of Sensory Systems
Based on the example of the visual system, the general principle underlying our neuro-sensory system can be described as below:
All sensory systems are based on
- a Signal, i.e. a physical stimulus, provides information about our surrounding.
- the Collectionof this signal, e.g. by using an ear or the lens of an eye.
- the Transductionof this stimulus into a nerve signal.
- the Processingof this information by our nervous system.
- And the generation of a resulting Action.
While the underlying physiology restricts the maximum frequency of our nerve-cells to about 1 kHz, more than one-million times slower than modern computers, our nervous system still manages to perform stunningly difficult tasks with apparent ease. The trick: there are lots of nerve cells (about 
), and they are massively connected (one nerve cell can have up to 150’000 connections with other nerve cells).
Transduction
The role of our “senses” is to transduce relevant information from the world surrounding us into a type of signal that is understood by the next cells receiving that signal: the “Nervous System”. (The sensory system is often regarded as part of the nervous system. Here I will try to keep these two apart, with the expression Sensory System referring to the stimulus transduction, and the Nervous System referring to the subsequent signal processing.) Note here that only relevant information is to be transduced by the sensory system! The task of our senses is NOT to show us everything that is happening around us. Instead, their task is to filter out the important bits of the signals around us: electromagnetic signals, chemical signals, and mechanical ones. Our Sensory Systems transduce those environmental variables that are (probably) important to us. And the Nervous System propagates them in such a way that the responses that we take help us to survive, and to pass on our genes.
Types of sensory transducers
- Mechanical receptors
- Balance system (vestibular system)
- Hearing (auditory system)
- Pressure:
- Fast adaptation (Meissner’s corpuscle, Pacinian corpuscle) ? movement
- Slow adaptation (Merkel disks, Ruffini endings) ? shape Comment: these signals are transferred fast
- Muscle spindles
- Golgi organs: in the tendons
- Joint-receptors
- Chemical receptors
- Smell (olfactory system)
- Taste
- Light-receptors (visual system): here we have light-dark receptors (rods), and three different color receptors (cones)
- Thermo-receptors
- Heat-sensors (maximum sensitivity at ~ 45°C, signal temperatures < 50°C)
- Cold-sensors (maximum sensitivity at ~ 25°C, signal temperatures > 5°C)
- Comment: The information processing of these signals is similar to those of visual color signals, and is based on differential activity of the two sensors; these signals are slow
- Electro-receptors: for example in the bill of the platypus
- Magneto-receptors
- Pain receptors (nocioceptors): pain receptors are also responsible for itching; these signals are passed on slowly.
Neurons
Now what distinguishes neurons from other cells in the human body, like liver cells or fat cells? Neurons are unique, in that they:
- can switch quickly between two states (which can also be done by muscle cells).
- That they can propagate this change into a specified direction and over longer distances (which cannot also be done by muscle cells).
- And that this state-change can be signalled effectively to other connected neurons.
While there are more than 50 distinctly different types of neurons, they all share the same structure:
a) Dendrites, b) Soma, c) Nucleus, d) Axon hillock, e) Sheathed Axon, f) Myelin Cell, g) Node of Ranvier, h) Synapse
- An input stage, often called dendrites, as the input-area often spreads out like the branches of a tree. Input can come from sensory cells or from other neurons; it can come from a single cell (e.g. a bipolar cell in the retina receives input from a single cone), or from up to 150’000 other neurons (e.g. Purkinje cells in the Cerebellum); and it can be positive (excitatory) or negative (inhibitory).
- An integrative stage: the cell body does the household chores (generating the energy, cleaning up, generating the required chemical substances, etc), combines the incoming signals, and determines when to pass a signal on down the line.
- A conductile stage, the axon: once the cell body has decided to send out a signal, an action potential propagates along the axon, away from the cell body. An action potential is a quick change in the state of a neuron, which lasts for about 1 msec. Note that this defines a clear direction in the signal propagation, from the cell body, to the:
- output Stage: The output is provided by synapses, i.e. the points where a neuron contacts the next neuron down the line, most often by the emission of neurotransmitters (i.e. chemicals that affect other neurons) which then provide an input to the next neuron.
Principles of Information Processing in the Nervous System
Parallel processing
An important principle in the processing of neural signals is parallelism. Signals from different locations have different meaning. This feature, sometimes also referred to as line labeling, is used by the
- Auditory system – to signal frequency
- Olfactory system – to signal sweet or sour
- Visual system – to signal the location of a visual signal
- Vestibular system – to signal different orientations and movements
Population Coding
Sensory information is rarely based on the signal nerve. It is typically coded by different patterns of activity in a population of neurons. This principle can be found in all our sensory systems.
Learning
The structure of the connections between nerve cells is not static. Instead it can be modified, to incorporate experiences that we have made. Thereby nature walks a thin line:
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Eskimo Curlew
- If we learn too slowly, we might not make it. One example is the “Eskimo curlew”, an American bird which may be extinct by now. In the last century (and the one before), this bird was shot in large numbers. The mistake of the bird was: when some of them were shot, the others turned around, maybe to see what’s up. So they were shot in turn – until the birds were essentially gone. The lesson: if you learn too slowly (i.e. to run away when all your mates are killed), your species might not make it.
Female Monarch butterfly
- On the other hand, we must not learn too fast, either. For example, the monarch butterfly migrates. But it takes them so long to get from “start” to “finish”, that the migration cannot be done by one butterfly alone. In other words, no single butterfly makes the whole journey. Nevertheless, the genetic disposition still tells the butterflies where to go, and when they are there. If they would learn any faster – they could never store the necessary information in their genes. In contrast to other cells in the human body, nerve cells are not re-generated in the human body.
Simulation of Neural Systems
Simulating Action Potentials
Action Potential
The “action potential” is the stereotypical voltage change that is used to propagate signals in the nervous system.
Action potential – Time dependence
With the mechanisms described below, an incoming stimulus (of any sort) can lead to a change in the voltage potential of a nerve cell. Up to a certain threshold, that’s all there is to it (“Failed initiations” in Fig. 4). But when the Threshold of voltage-gated ion channels is reached, it comes to a feed-back reaction that almost immediately completely opens the Na+-ion channels (“Depolarization” below): This reaches a point where the permeability for Na+ (which is in the resting state is about 1% of the permeability of K+) is 20*larger than that of K+. Together, the voltage rises from about -60mV to about +50mV. At that point internal reactions start to close (and block) the Na+ channels, and open the K+ channels to restore the equilibrium state. During this “Refractory period” of about 1 m, no depolarization can elicit an action potential. Only when the resting state is reached can new action potentials be triggered.
To simulate an action potential, we first have to define the different elements of the cell membrane, and how to describe them analytically.
Cell Membrane
The cell membrane is made up by a water-repelling, almost impermeable double-layer of proteins, the cell membrane. The real power in processing signals does not come from the cell membrane, but from ion channels that are embedded into that membrane. Ion channels are proteins which are embedded into the cell membrane, and which can selectively be opened for certain types of ions. (This selectivity is achieved by the geometrical arrangement of the amino acids which make up the ion channels.) In addition to the Na+ and K+ ions mentioned above, ions that are typically found in the nervous system are the cations Ca2+, Mg2+, and the anions Cl- .
States of ion channels
Ion channels can take on one of three states:
- Open (For example, an open Na-channel lets Na+ ions pass, but blocks all other types of ions).
- Closed, with the option to open up.
- Closed, unconditionally.
Resting-state
The typical default situation – when nothing is happening – is characterized by K+ that are open, and the other channels closed. In that case two forces determine the cell voltage:
- The (chemical) concentration difference between the intra-cellular and extra-cellular concentration of K+, which is created by the continuous activity of the ion pumps described above.
- The (electrical) voltage difference between the inside and outside of the cell.
The equilibrium is defined by the Nernst-equation:
R … gas-constant,
T … temperature,
z … ion-valence,
F … Faraday constant,
[X]o/i … ion concentration outside/ inside.
At 25° C, RT/F is 25 mV, which leads to a resting voltage
With typical K+ concentration inside and outside of neurons, this yields . If the ion channels for K+, Na+ and Cl- are considered simultaneously, the equilibrium situation is characterized by the Goldman-equation where Pi denotes the permeability of Ion “i”, and I the concentration. Using typical ion concentration, the cell has in its resting state a negative polarity of about -60 mV.
Activation of Ion Channels
The nifty feature of the ion channels is the fact that their permeability can be changed by
- A mechanical stimulus (mechanically activated ion channels)
- A chemical stimulus (ligand activated ion channels)
- Or an by an external voltage (voltage gated ion channels)
- Occasionally ion channels directly connect two cells, in which case they are called gap junction channels.
Important
- Sensory systems are essentially based ion channels, which are activated by a mechanical stimulus (pressure, sound, movement), a chemical stimulus (taste, smell), or an electromagnetic stimulus (light), and produce a “neural signal”, i.e. a voltage change in a nerve cell.
- Action potentials use voltage gated ion channels, to change the “state” of the neuron quickly and reliably.
- The communication between nerve cells predominantly uses ion channels that are activated by neurotransmitters, i.e. chemicals emitted at a synapse by the preceding neuron. This provides the maximum flexibility in the processing of neural signals.
Modeling a voltage dependent ion channel
Ohm’s law relates the resistance of a resistor, R, to the current it passes, I, and the voltage drop across the resistor, V:
or
where is the conductance of the resistor. If you now suppose that the conductance is directly proportional to the probability that the channel is in the open conformation, then this equation becomes where gmax is the maximum conductance of the cannel, and n is the probability that the channel is in the open conformation.
Example: the K-channel
Voltage gated potassium channels (Kv) can be only open or closed. Let α be the rate the channel goes from closed to open, and β the rate the channel goes from open to closed Since n is the probability that the channel is open, the probability that the channel is closed has to be (1-n), since all channels are either open or closed. Changes in the conformation of the channel can therefore be described by the formula.
Note that α and β are voltage dependent! With a technique called “voltage-clamping”, Hodgkin and Huxley determine these rates in 1952, and they came up with something like.
If you only want to model a voltage-dependent potassium channel, these would be the equations to start from. (For voltage gated Na channels, the equations are a bit more difficult, since those channels have three possible conformations: open, closed, and inactive.)
Hodgkin Huxley equation
The feedback-loop of voltage-gated ion channels mentioned above made it difficult to determine their exact behaviour. In a first approximation, the shape of the action potential can be explained by analyzing the electrical circuit of a single axonal compartment of a neuron, consisting of the following components: 1) membrane capacitance, 2) Na channel, 3) K channel, 4) leakage current:
The final equations in the original Hodgkin-Huxley model, where the currents in of chloride ions and other leakage currents were combined, were as follows:
Spiking behavior of a Hodgkin-Huxley model.
where m, h, and n are time- and voltage dependent functions which describe the membrane-permeability. For example, for the K channels n obeys the equations described above, which were determined experimentally with voltage-clamping. These equations describe the shape and propagation of the action potential with high accuracy! The model can be solved easily with open source tools, e.g. the Python Dynamical Systems Toolbox PyDSTools. A simple solution file is available under [1] , and the output is shown below.
Modeling the Action Potential Generation: The Fitzhugh-Nagumo model
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Phaseplane plot of the Fitzhugh-Nagumo model, with (a=0.7, b=0.8, c=3.0, I=-0.4). Solutions for four different starting conditions are shown. The dashed lines indicate the nullclines, and the “o” the fixed point of the model. I=-0.2 would be a stimulation below threshold, leading to a stationary state. And I=-1.6 would hyperpolarize the neuron, also leading to a – different – stationary state.
The Hodgkin-Huxley model has four dynamical variables: the voltage V, the probability that the K channel is open, n(V), the probability that the Na channel is open given that it was closed previously, m(V), and the probability that the Na channel is open given that it was inactive previously, h(V). A simplified model of action potential generation in neurons is the Fitzhugh-Nagumo (FN) model. Unlike the Hodgkin-Huxley model, the FN model has only two dynamic variables, by combining the variables V and m into a single variable v, and combining the variables n and h into a single variable r
I is an external current injected into the neuron. Since the FN model has only two dynamic variables, its full dynamics can be explored using phase plane methods (Sample solution in Python here [2])
Simulating a Single Neuron with Positive Feedback
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Let us first look at the response of a single neuron, with an input x(t), and with feedback onto itself. The weight of the input is v, and the weight of the feedback w. The response y(t) of the neuron is given by
y(t)=wy(t-1)+vx(t-1)
This shows how already very simple simulations can capture signal processing properties of real neurons.
Conditions of formation of conditioned reflexes
- The combination of probation with the unconditioned stimulus.
- The prevalence of absolute power over the conditioned stimulus.
- Indifference signal stimulus, its repeatability to disappear orienting reaction.
- Conditional (signal) must be preceded by the unconditional stimulus.
- No extraneous stimuli (soundproof camera, “Tower of Silence”).
- Normal operation crust.
Pavlovskaya uslovnoreflektoranya theory had a revolutionary impact on almost without exception, the science of brain activity – memory, emotions, instincts, the nature of sleep, the individual features of nervous activity, the impact on the brain of drugs.
- The formation of a temporary connection begins with “summation reflex” (bannung – reflex beaten path Pavlova), the phenomenon of imprinting – is firmly fixed information births).
- The excitation in the cortex goes from weak to strong hearth – the principle of dominant Ukhtomskogo (confirmed. Dzhurdzhea, 1959; Asratyan, 1963).
If you originally anticipated closure of a temporary connection between the cortical elements exclusively, but now between the cortical end of the analyzer and the subcortical center of the unconditioned reflex. Then again between cortical elements – an unconditioned reflex and analyzer. But as consolidation occurs reflex arc reflex movement at the subcortical level.
Hypothesized closure temporary connection at the neuronal level.
- (Fessard, Gastaut, Roger, 1962 – in the neurons of the Russian Federation), and the projection area of the cerebral cortex shew braking effect on the network structure. SD may be formed in cats and dogs bark when removing some stimulus, are the basis perhaps non-specific thalamic nuclei (reborn., Specificity.), RF midbrain. But it is produced slowly, with a long and strong irritant. But these mechanisms are constantly include uslovnorefletornuyu activities. The conditioned reflex – updated trace memory (temporary connection), a natural and necessary condition of its formation and manifestation.
- The hypothesis of a convergent mechanism circuit temporary connection, according to which the process is reduced to the interaction of stimuli at subsynaptic chemically heterogeneous membranes, ie, chemical interaction in the molecular organization axoplasm (Grunsfest, Bulloh, Anokhin, 1961).
Integration of irritation at the level of one neuron (trace elements) by entering into chemical interactions include general metabolic processes axoplasm etc. (There multivarentnye neurons respond to light, sound, polevlentnye – within one analyzer).
Neuron – a complex system capable of convergence pulses. No matter topographical proximity centers of excitation.
Stimulation of different biological active modality same neuron through different neurochemical mechanisms: food – cholinergic, pain – adrenergic perhaps at the molecular level. Fixing memory traces completed structurally fixed neural konstelyatsiey.
First: 1) generalization, generalization of conditioned reflexes (focus of increased excitability), and 2) specialty – the transition of total tracks excitations in the microstructure.
This is explained not only by the concentration and irradiation of transcortical mechanism, but also as a result of inclusion of activating mechanisms of subcortical structures.
In the early phase of development of conditioned reflexes temporary connection is maintained functional shifts to include the following mechanisms.
- Long-term circulation of neural excitation in closed circuits (reverb in neural circles Lorente de).
- Inactive synapses become active due to the mechanisms of post-tetanic potency (Kostyuk, Eccles, Wilson). There is an increase in the intracellular concentration of electrolytes, which helps the flow of water into the cell. Cell swells and narrows the gap between pre- and postsynaptic membranes, facilitated synaptic conductivity. “Potential” synapses become “urgent”.
In the following functional changes go into structural biochemical changes.
- Communication “sprout”, dendritic growth, the emergence of spines on the processes of neurons, increased ties (morphological changes).
- Glial cells perform trophic support function may be involved in the formation of a temporary connection by “myelination naked” presynaptic axon terminals, improving the conductivity.
- There is a change of protein synthesis in the cell, excitation encoded in RNA, base composition varies.
- It should be fixed on the molecular DNA that keeps track of longer than quickly synthesized RNA.
- Thus, 3 and 4 explain the implementation of temporary connection through qualitative and quantitative changes in protein synthesis.
- The mechanism of formation of temporary connections there are changes in the system of enzymes and their inhibitors.
Transition from short-term to long-term memory – consolidation – is involving the limbic system (the hippocampus).
The formation of a temporary connection – is primarily an explanation of neural processes that occur in the brain under the influence of external and internal stimuli, some restructuring of existing and creation of new intercentral relations.
Remembering imprinting – the formation of a temporary memory svyazisled – engram.
Thus, the excitement of the conditioned and unconditioned stimuli can converge in different cortical areas, and from there flow to the executive bodies. This can occur in any part of the cortex. Possibly, there are multiple paths circuit, which is used in one or the other. Reaching a certain degree of organization they receive a subjective reflection, they are worried mental nerve processes.
Now study the GNI, combining subtle neurophysiological research and the conditioned reflex method in the same laboratory. Although there is still a gap between the physiology and psychology of GNI. Since The more neuroscientist explores subtle and profound processes of the nervous system, the farther away from the understanding of the whole brain, mental activity, etc.
Changes in the body’s relations with the outside world changes and experiences (pain stimulation in the dog – conditioned food pathogen rather than nociceptive).
Consequently, the formation is the formation of a new SD nervous integration of new nerve whole process, which is reflected as a subjective) mental experience).
The conditioned reflex – a specialized case of the universal laws, which in a primitive form of stabilization chain of chemical processes appeared at the stage of primitive beings.
Anticipatory reflection of reality – warning alarm, because option in the evolution of time and frequency, repeatability durable – spatial and temporal characteristics.
Pavlov opened the signal value and reinforcing factor signaling pathways in the form of conditioned reflexes, as unconditioned reflexes can not provide long-term, lasting and perfect fit to the animal organism constantly changing conditions, for out of the total mass of the agents of the outside world, they are caused by a relatively small number of stimuli.
The set of UR GNI, as “universal” mechanism of individual adaptation, which provides the finest and varied relationship with the environment.
UR is the highest form of temporary connection in conjunction with the mental act – feeling. This actualization of the memory trace (temporary connection). Temporary Us – structurally fixed neural constellation, which is embodied individual experience of the body.
The cerebral cortex is constantly carries out the analysis and synthesis of phenomena and the internal environment.
The analysis is carried out analyzers – the difference, division, differentiation of the different effects on the body.
Synthesis – is the integration, summation, ie, association, generalization of fragmented elements of analysis in a single nervous process. This is based on the ability of the cerebral cortex to develop under the influence of certain external influences moving the order of the main processes – temporal relationship as the basis for elaboration of the conditioned reflex and the dynamic stereotype – a more complex form of synthetic activity of the cortex.
The environment variable, but its influence are characterized by repetition, a specific sequence (the day gives way to night, is characterized by certain successive shifts). Such changeable order of different stimuli is designated “outside the stereotype.” Cora reflects the impact of such a system in the form of work – a dynamic stereotype – balanced and secure system of conditioned and unconditioned reflexes. This specific sequence and intensity occurring in the crust of excitation and inhibition.
Dynamic stereotype based on the following, which remain in the cerebral cortex after exposure to each of the preceding exposure and a certain way combined with neural processes that occur under the influence of subsequent irritation. This is an example of the analytic-synthetic function of the cortex, where the interaction of different analyzers, ie bark acts as a single unit.
The stereotype of “dynamic” because it is broken when the external stereotype and can be replaced by others. The reaction proceeds in a qualitatively stimulus itself, and in its place in the system complex stimuli. Dynamic stereotype – can be destroyed and formed again. Dynamic stereotype creates a crust on the installation of a certain degree of excitatory or inhibitory state and neural processes are easier to automatically conditioned reflex activity is facilitated.
All our skills (skiing, skating, playing guitar, piano, etc.), Work activity – automatic operation, it is a dynamic stereotype that frees cortical centers to solve more complex problems.
Thus, the conditioned reflex – it is a natural reaction to the previously neutral stimulus, which reproduces the unconditioned reflex (classical SD), or the movement, which is essential for reinforcement (instrumentalnyyUR). The conditioned reflex – functional unit of activity of higher parts of the brain.
At the heart of SD is the formation of new or modification of existing neural connections that happens in the individual life of animals and humans due to changes in external and internal environment. This temporary connections that inhibited the abolition of reinforcement.
Conditioned stimulus may be any change in the environment or the internal state of the body has reached a certain intensity, and perceived the cortex of the cerebral hemispheres.
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