ISBN
978-3-00-064888-5
Monograph of Dr. rer. nat. Andreas Heinrich Malczan
The basal ganglia system of vertebrates has an extremely complex structure and is composed of many substructures. It cannot simply have developed as a whole, but must - like all other substructures of the vertebrate brain - have developed gradually.
An important subsystem of the Basal Ganglia is the substantia nigra pars compacta. It is one of several mean systems of the entrance level of the primordial brain of the segmented Bilateria, whose lines lead to the vertebrates. This mean value centre uses the transmitter dopamin. It is originally located at about the level of the nucleus ruber, which is the output nucleus of this level. Also there are the input nuclei of the trunk, in vertebrates the nucleus cuneatus and gracilis as well as other mean-value nuclei. Like all these nuclei, the substantia nigra pars compacta is also present bilaterally, i.e. on each half of the body.
Mean value systems have a basic property:
In mean value systems, all signals of the system must be recorded as far as possible so that each of them contributes to the generated mean value.
We postulate here that in early primeval times there were as many class 5 neurons as class 6 neurons, i.e. for each cortical output neuron of class 5 there was exactly one class 6 mean value neuron, which took over its excitation and projected it to the mean value centers.
In the lower section of the thalamic level - the second section of each rope ladder system - a mean centre developed, from which the later nucleus subthalamicus emerged. The mean neurons present in the sixth neuron layer of the cortical floor took over their excitation from the output neurons of class 5 and projected (also) into this subthalamic mean nucleus, which was located slightly below the thalamic nuclei.
The nucleus subthalamicus is an average nucleus below the thalamic level. Class 6 cortical mean neurons project excitably into this nucleus, which represents a topological mean model of the cortical floor. It excitably projects into the dopaminergic mean nucleus so that it contains a subarea that also represents a mean model of the cortical floor.
It should be remembered that in the olfactory modality range the septum already existed as the mean core. Likewise, a dopaminergic mean nucleus, the substantia nigra pars compacta near the nucleus ruber, also existed in the basal layer of the primordial brain. He used the transmitter dopamine. Initially, these centres certainly consisted of very few neurons, but they were absolutely necessary for further development in the direction of vertebrates. Both nuclei received the output of the cortex.
The substantia nigra pars compacta received as input the descending motor output of the early primal brain. It was initially a model of cortical excitation.
The nucleus subthalamicus received as input the descending motor output of the early primal brain.
Thus both the dopaminergic substantia nigra pars compacta and the glutamatergic nucleus subthalamicus received the same input from the cortical mean neurons.
Between the cortical neurons of class 5 there was a lateral neighbour inhibition, which was realized by GABAergic interneurons.
These three conditions were sufficient for the development of an early basal ganglion system. The cause was the back projection of the mean value centres into the regions of origin of their signal suppliers.
We now recall an important task of mean nuclei. Each mean-value nucleus primarily generates a mean-value signal, which serves to control the most important life processes. But secondarily a mean-value centre also serves to activate its signal suppliers. Therefore, there is (usually) an exciting back projection from the center to the structure that provided the input. However, the back projection is mostly only activating, it raises the excitation threshold without generating own action potentials.
In the case of the substantia nigra, this rule has been neglected in the course of evolution. After a certain stage of development, this dopaminergic rear projection became independent and became specific. In the end, each input signal in the substantia nigra pars compacta was merely switched to dopamine and returned with the same rate of fire, exactly in the direction of its origin.
In the basal ganglia system, each input signal that reaches the substantia nigra pars compacta is passed to a dopaminergic projection neuron, which projects it back towards its original origin while maintaining its rate of fire.
The dopaminergic axons of the neurons of the substantia nigra pars compacta were only very weakly or not at all myelinated, and their length was - depending on the body size of the living being - sometimes quite considerable. Therefore, any action potential on them needed a certain time to reach its destination. Thus a time delay was imposed on these signals. The substantia nigra was thus a delay core.
The substantia nigra pars compacta is a delay core and a switch core. It switches the input signals from the cortex to dopamine and sends them back to the cortex, thus causing a short-term delay.
In the cortex, the dopaminergic rear projection had an exciting effect on the class 1 neurons that received it and thus activated the cortical neurons in the environment. Thus, the excitation of the mean centre increased the response threshold of the cortical neurons.
There was competition between the class 5 cortical neurons. Each of them had its own inhibitory interneuron to which it was excitably coupled. This is what we call here the assigned inhibitory neuron. This had a larger axon tree and synaptically contacted the neighbouring class 5 output neurons to (relatively) inhibit them. This corresponded to a lateral inhibition and served to increase the contrast between the output signals of the class 5 neurons. This lateral neighbor inhibition existed from the beginning and was maintained when the modality loops were unfolded and the parietal, temporal and occipital loops were created. In each of them there was the lateral inhibition by GABAergic interneurons and an activating rear projection from the dopaminergic mean nucleus, the substantia nigra pars compacta.
In the course of evolution, however, there were also interactions of the returning dopaminergic axons with these inhibitory GABAergic interneurons, which provided lateral inhibition and thus contrast enhancement between the class 5 cortical output neurons. The GABAergic interneurons had to develop receptors for dopamine. The dopamine receptor D2 caused the dopaminergic axons to excite the inhibitory interneurons, as did the associated glutamatergic cortex neuron.
The dopaminergic axons found suitable contact partners in the inhibitory interneurons of the cortex. Each cortical partner had a corresponding inhibitory neuron with which it was synaptically connected. There was a signal relationship. This made it easier for the dopaminergic axons to find their targets. They docked with them. And that's how the function of those inhibitory interneurons in the cortex changed. We will refer to them briefly as inhibitory neurons.
The cortical excitation of an inhibitory neuron by the assigned class 5 cortexneuron was gradually reduced and (in the course of a longer evolutionary process) completely ceased.
Instead, the excitation came via the dopaminergic detour: the cortex neuron projected into the substantia nigra pars compacta, where the signal was switched to dopamine and now in turn activated the inhibitory neuron.
Initially, this did not result in a disadvantage. It was as if a further neighboring inhibition had now been added to the original neighboring inhibition. This was due to the point-to-point projection.
At the same time, the inhibitory synapses of the striatum neurons, which previously inhibited the neighbouring cortex neurons, were reduced. Whereas the axons of the inhibiting interneurons used to branch out more strongly and inhibit neighbouring cortex neurons, the striatum neurons gradually lost these axon branches completely.
Instead, a single projection axon developed in each striate neuron, which, like the other projection axons in this region, also strove downward. The striate neurons were treated like the downward projecting class 5 connective neurons.
Thus, a new class of inhibitory neurons was created on the first floor from the originally existing interneurons. They received the returning dopaminergic excitation of the substantia nigra pars compacta. We will (with good reason) call these neurons striosome neurons. Their signals were signal-related to the cortex signals, because they emerged from them by a transmitter switch from glutamate to dopamine. These neurons took over the directional selectivity from the cortex neurons to the marker that made the axons grow downwards. Therefore, they developed (in the course of evolution) - just like the cortex neurons - downward projecting axons, which also moved to the nucleus ruber. They simply followed the responsible gradient gradient of the directional marker. Once there, each axon docked - in a point-to-point mapping - exactly to the neuron that received the axon of the signal-related cortex signal. Because it used the transmitter GABA, the output neuron in the nucleus ruber was now additionally inhibited. Exactly this was an enormous advantage.
The population of inhibitory interneurons in the cortex, which realized a lateral neighbor inhibition between the class 5 neurons, disappeared completely by this process, as did the contralateral one. The inhibitory interneurons were missing, which now functioned as projection neurons for the striatum. Therefore, the contralateral inhibition was shifted to the thalamic level, as has already been described.
In later evolutionary time another structure, the matrix, should be formed. Both, matrix and striosomes, form the striatum in modern vertebrates. The striosome structure was the first to form at a very early stage of development.
The striosomal neurons are descendants of the inhibitory interneurons of the first, cortical segment, which are responsible for lateral inhibition and thus for contrast enhancement of descending cortex signals. They receive the excitatory dopaminergic back projection from the substantia nigra pars compacta and project inhibitory to the nucleus ruber.
This development took place in parallel in the parietal, temporal and occipital loops, and later also in the frontal loop.
What was the advantage of each output neuron in the nucleus ruber receiving exactly one cortex signal on the one hand and the inhibition signal derived from it on the other? Actually, both were identical, so that (assuming the same signal strength) the zero signal should have been generated, which was worthless.
The benefit was the short time delay caused by dopaminergic effects. This was because the inhibitory signals had also travelled a distance that corresponded to twice the distance between the first and seventh floor. In this respect, the dopaminergic core was a delay core.
If the signal of the cortex neuron concerned had not changed in the meantime, the zero signal was now present in the responsible neuron of the nucleus ruber (assuming complete inhibition). Only if the glutamatergic present signal was stronger than the GABAergic past signal, a sufficient residual signal remained despite the inhibition. This signal was the difference signal between present and immediate past. Its target neurons were in turn the motor neurons, so that the difference signal triggered motor responses that had not existed before.
Living beings with such a differential circuit now reacted much more strongly to changes in signals over time. Temporal changes are, among other things, the result of movements. If an object moves, this changes the signals registered by the sensors. Moving objects could now be perceived in many different ways, such as olfactory, tactile, acoustic or visual. A slight increase in the corresponding signal strength was sufficient for perception. This could be observed when prey approached, which could now be more easily detected. The same was true for predators, which could now be avoided because their approach was perceived.
Since this differential circuit referred to signals from the parietal, temporal and occipital loops, all modalities of the living being were integrated into the movement and change detection.
The inhibitory neurons of the first floor, which received the excitatory, dopaminergic delayed input and sent it inhibitory to the nucleus ruber, formed the original form of the vertebrate striatum, which initially consisted only of the striosomes. The striosome neurons are excited by the transmitter dopamine because they possess the dopamine receptor D2. They themselves use the inhibitory transmitter GABA.
Later, the matrix system was added as a second subsystem. The matrix neurons possess the dopamine receptor D1, therefore they are inhibited by the dopaminergic input. Their transmitter is also GABA.
Both striosome neurons and matrix neurons are still present in the striatum of modern vertebrates. We also find them in mammals. Thus, the striatum of modern mammals consists of two compartments, called striosomes and matrix. The striosomes are in the minority and are distributed in the striatum like raisins in a cake. Exactly these striosome neurons are still excited by the substantia nigra and project via the tractus tegmentalis centralis inhibitingly into the nucleus ruber, as they have been doing since time immemorial.
The primordial triatum consisted only of the striosomes. Their neurons received a complete copy of the output of the first, cortical segment of the bilateral stripline system via the detour of the dopaminergic mean nucleus of the seventh segment. Since they used the dopamine receptor D2, they were excited by the input. Their output, via the transmitter GABA in the output segment of the primordial brain, in the nucleus ruber, topologically well ordered inhibited the output neurons that received the same cortical signal in excitatory form. The time difference between excitatory and inhibitory signals resulted in a differential mappingthat reacted selectively to changes and was thus able to detect movements that led to motor responses across all sensory modalities. The substantia nigra pars compacta assumed the role of a dopaminergic delay nucleus.
We had divided the neurons into neuron classes as well as the signals into signal classes. Analogously, we can divide the time-sensitive difference maps in the primordial brain into signal classes. Then the time-sensitive differential mapping of class 5 is assigned to the nucleus ruber. The inhibitory, time-delayed branch of this differential mapping is formed in the striosomes of the primordial brain, the excitatory branch is transferred from signal class 5 of the primordial brain to the nucleus ruber.
Thus the nucleus ruber suffered a functional change. While it was previously the initial nucleus of the primeval brain, it now became the material seat of the time-sensitive differential mapping and allowed motor responses to changes of all kinds that had previously been impossible.
With the formation of the early basal ganglia system a functional change occurred in the nucleus ruber. Although it was still the initial nucleus of the primordial brain and its signals controlled the motor neurons of the body, it now also served to detect changes of all kinds and generated new motor responses via a time-sensitive differential mapping.
In later developmental epochs on the way to vertebrates, the differential mapping in the nucleus ruber was supplemented by another in a new neuron nucleus, which belongs to the thalamic group. In later development, the matrix neurons in the striatum developed, which inhibit the projection into these thalamic regions. This is described in more detail in later chapters.
The entire system consisting of striatum, substantia nigra pars compacta and several other subsystems is called the basal ganglion system.
Movement and change
detection in the developing basal ganglia system of vertebrates is based on the
comparison of the signal strength of past and present signals. Here the past
signals have an inhibitory effect, the present signals have an excitatory
effect. The past signals are derived from the present signals by delaying them
for an additional detour and turning them into past signals.
A transmitter switch from dopamine to GABA gives them an inhibitory effect. The
comparison took place directly in the nucleus ruber in primitive evolutionary
times and led to additional motor responses to changes. Later on, own comparison
nuclei developed in the thalamic level.
The basal ganglia of the vertebrate brain enable the detection of movement and change by comparing past signals with present signals. The past signals result from a time delay of present signals on additional path sections of the dopaminergic system. The past signals inhibit the present signals, so that the increase in excitation of present signals as well as the decrease in excitation of past signals during signal strength comparison results in an exciting differential signal which can trigger additional motor activities. In the original basal ganglia system, the striatum consisted only of striosomes and had an inhibitory effect in a point-to-point imaging into the nucleus ruber, which was the motor output nucleus.
Regarding the inhibitory effect, we can assume that the synaptic coupling of the neurons of striatum and nucleus ruber was initially low and slowly increased over the course of innumerable generations. The initially low inhibitory effect increased steadily in the course of evolution. At the same time, the ability to recognize movement grew slowly and steadily, thus leading to an evolutionary advantage. Creatures with a stronger synaptic coupling between these neurons had a clear advantage in the recognition of movement.
For the abbreviated representation of neuron chains we introduce the following symbolic representation, which we refer to as the short form:
Each neuron (or group of neurons) involved is identified by the nucleus or neuron layer, followed by the transmitter and the type of excitation (+,-), all in round brackets.
2. The elements of the chain are separated by arrows indicating the direction of propagation.
Then the neuron chain for the striosomes, which begins in the cortex, is described as follows:
Striosome projection:
(cortex 5, glutamate, +) → (substantia nigra pars compacta, dopamine, +) → (striosomes, GABA, -) → (nucleus ruber, glutamate, +)
However, one should not
forget the mean value projection via the same path
Mean value projection:
(cortex 6, glutamate, +) → (substantia nigra pars compacta, dopamine, +) → (striosomes, GABA, -) → (nucleus ruber, glutamate, +)
The Tractus tegmentalis centralis from the striatum to the nucleus ruber and further to the nucleus olivaris should play an important role later - when a Cerebellum developed. The signals emitted by the striosome system via this tract formed the class of climbing fibre signalsin the Pontocerebellum many millions of years later. These became the basis of the learning ability of this new structure. This will be further developed in chapter 4.
When the matrix system developed much later in the striatum, its projection axons were integrated into the existing Tractus tegmentalis centralis.
The projection from the striosomal neurons via the nucleus ruber to the nucleus olivaris is called tractus tegmentalis centralis and represents the projection of the cortical floor into the climbing fiber system of the cerebellum. It is the material prerequisite for the development of the pontocerebellum of vertebrates.
This example shows that various structures of the early brain already existed, although the connecting structures had not yet developed. Thus, at the stage of development described here, there was no real cerebellum at all, but only its precursor in the form of the Purkinje nucleus, the latter initially being an accumulation of inhibitory projection neurons and serving as a contralateral inhibition of motor opponents. But the important tractus tegmentalis centralis had already developed.
The axons moving from the striatum towards the nucleus ruber passed two already existing mean nuclei on their way and virtually passed through them. The upper one was the nucleus subthalamicus, the lower one the substantia nigra pars compacta. Both were tonically excited by the influx of cortical excitation. To avoid harmful overexcitation, the striatal axons made synaptic contact with the mean neurons of both nuclei and inhibited them. Such excitation limitations are found in many substructures of the vertebrate brain.
On their way to the nucleus ruber, the striosomal neurons of the early striatum projected via collateral inhibitors into the nucleus subthalamicus and into the substantia nigra pars compacta. This limited their excitation by the cortical signals.
The inhibitory projection of the striatum into the nucleus subthalamicus laid the foundation for the later cleavage of a new nucleus known as globus pallidus. It is a descendant of the inhibitory interneurons of the subthalamic nucleus, which were used for lateral inhibition and thus for contrast enhancement. They were excited (tonic) by the neurons of the subthalamic nucleus and inhibited by the striatum. Their rear projection reached the thalamic level. The inhibiting interneurons of the substantia nigra pars compacta underwent a similar development, with the substantia nigra pars reticularis as the new nucleus. But this development first required the formation of a cerebellum.
Monograph of Dr. rer. nat. Andreas Heinrich Malczan