ISBN
978-3-00-037458-6
ISBN 978-3-00-042153-2
Monograph of Dr. rer. nat. Andreas Heinrich Malczan
It has already been mentioned several times that the matrix of the striatum projects excitatory acetylcholine onto the neurons of the striosomes with the help of the transmitter. The projection paths are relatively simple. The dopaminergic neurons of the nigrosomes from the substantia nigra project excitatory into the striatal striosomes. In contrast, the dopaminergic neurons of the nigral matrix project dopamine into the matrix of the striatum via the transmitter. This matrix contains the GABAergic main neurons with their D2 receptors, which means that dopamine has an inhibitory effect on these matrix neurons.
But the matrix also contains - in large numbers - acetylcholinergic interneurons, which are apparently excited by the dopaminergic axons from the nigral matrix. After all, the dopaminergic input is the only input they receive. There are no reports in the literature about tapping the glutamatergic cortex output - which passes through this area. The dopaminergic axons of the nigral matrix, which end in the striatal matrix, project excitatory acetylcholine via the transmitter onto the nearby cholinergic interneurons, which in turn project directly and excitatory into the striosomal neurons. As a result of this cytoarchitectonic structure, the matrix is rich in acetylcholine, while this transmitter is very little present in the striosomes of the matrix.
A system-theoretical explanation of this projection could be a touchstone for the fundamental correctness of the theory of the brain as drafted by the author of this monograph. After many unsuccessful attempts, an explanation by the author that argues from an evolutionary point of view seems to prevail.
It is known that the outer layers of the brain are the evolutionarily younger ones. So the cerebrum, or more precisely the cerebral cortex, was formed later than the inner part. Therefore, one should be able to imagine that there was once a brain state in which there was no cerebral cortex at all. Only the inner, deeper nuclei of the cerebrum may have been present at that time.
And of course there was the cerebellum. It probably worked just like it does today, because from an evolutionary point of view it is an ancient system with a very conservative way of functioning. This can be seen from the fact that the cerebellums of lower organisms hardly differ from those of higher organisms when comparing cytoarchitectonics. However, if there was a cerebellum in primeval times that functioned roughly as it does today, then there was also the climbing fibre system. This is because the cerebellum only learns through the climbing fibres. These are a function-determining element of the system.
In this respect, there must have been a procedure that ensured the generation of the necessary climbing fibre signals even before primeval times - when there was no cerebrum. Some creatures with a missing or only very sparse cerebral cortex have managed to escape into the present, and are therefore not extinct. Their cerebellum uses a climbing fibre system. This system could have created the climbing fibres according to the same principle as in the present cerebellum: by averaging the already existing input. What is needed are large, averaging neurons, which are excited by the other neurons in a quasi integrative way. Due to the attenuation of the excitation during its spatial propagation within the interference areas, receptive fields are generated. In each case, a large averaging neuron is surrounded by a spherical receptive field whose neurons excite this averaging neuron. It is only necessary to decide which transmitter should be used and which neuron takes over which task if there is not to be a cerebral cortex.
The author of this monograph claims that the excitatory transmitter is acetylcholine. The climbing fibre signals were thus formed in primeval times within the striatum. This is where the large mean value neurons were formed, which integratively collected the excitatory input of the accessible neuro-nerves. This input came from the matrix of the substantia nigra. It reached the matrix as a dopaminergic input and excited the numerous interneurons whose excitation was transferred to the striosomal neurons with the help of the transmitter acetylcholine. The striosomal neurons thus formed mean signal values from the input, which they received from the nigral matrix via the cholinergic interneurons. This mean signal did not require a cortex cortex, and at this stage of evolutionary development, the cortex cortex did not even exist. Nevertheless, in the end there were the large, averaging striosomenneurons from which the rest of the basal system derived the climbing fibres.
And just like the cortex, there were clusters in the striatum. A cortex cluster consists of a mean neuron and the signal neurons of the cortex layer surrounding this neuron. It is analogous in the striatum. The centre of a striatum cluster is the gabaerge mean neuron. The cholinergic interneurons are arranged in a sphere around it and excite this mean value neuron with the help of the transmitter acetylcholine. The excitation of such a striatal mean value neuron is of course only sufficiently strong if the mean value-providing interneurons are sufficiently active. Therefore, this striatal mean-value neuron is also - like its cortical counterpart - an activity neuron. It is partly involved in the brain system where neuronal activities take place. And if there is such activity, the associated and strong mean-value signal is converted into a climbing fiber signal. No cerebral cortex is needed for this.
The excitation of the gabaergic striosomal mean neuron is supplied to the globus pallidus inter-na. The input rising in the system - which ends in the matrix because there is no cerebrum yet - is integratively combined as usual in the nucleus subthalamicus to one (or more) single signals. This single signal permanently excites the globus pallidus interna. However, since the gigaerge input from the striosomal mean neuron arrives at the same time, the formed mean value is negated at the single signal. This once negated mean value signal reaches the then existing nucleus ruber as the gigaergic input. We know from the latter that it is also an evolutionary ancient nuclear system. It has always received the descending signals from the brain. In this case, however, it is not the descending signals of the cortex cortex, because these did not exist before primeval times. Rather, the descending signals were formed in the striatum, from where they reached the nucleus ruber via descending projections, among other things, in order to move on from there towards the spinal cord.
Furthermore, the nucleus ruber has always received the excitatory, ascending signals from the Formatio reticularis.
Therefore, the nucleus ruber could use these ascending signals to form its own internal single signal from them with large mean neurons. The magnocellular part of the nucleus ruber required for this is evolutionarily ancient and already present in birds, as can be seen from a dissertation on chicken birds supervised by Prof. Karl Zilles.
The mean value signal of the striosome system, which has already been negated once in the globus pallidus interna, is now negated for the second time at the input signal of the nucleus ruber. The double negation leads to an increase in frequency and a significant time delay in the striosomal mean value signal.
Finally, the doubly negated, frequency-transformed and time-delayed mean value signal is fed to the olive, which sends it as a climbing fiber signal to the Purkinje cells of the associated Cerebellum cluster. There this climbing fiber signal leads to the storage of new complex signals. However, these do not originate from the cerebral cortex, but from the striatum.
The compartmentalisation that already existed at that time is clearly visible. Clusters in the striatum consist of matrix areas in which the averaging striosomal neurons are embedded. The compartmentalization continues to the cerebellum and is also present in the nucleus ruber. A gabaergic projection of the cerebellar nuclei towards the olive inhibits the climbing fiber signal in case the current signal is already a signal of a Purkinje cell. The output of the cerebellar nuclei reaches - via the thalamus - the striatum - only later does it move on towards the newly developing cerebral cortex.
Thus, the acetylcholinergic projection of the matrix of the striatum onto the striosomes of the striatum fits quite well into the evolutionary developmental scheme of the author. Let others judge whether everything happened in primeval times in this or a similar way.
One important aspect should be pointed out here: The magnocellular matrix system with the striosomal mean neuron was evolutionarily the oldest climbing fibre system in the world. In this system there was no direct projection of the matrix neurons into the cerebellum. Only the striosomal neurons had access to the climbing fibres via the globus pallidus interna and the nucleus ruber and led to the storage of statistically significant complex signals in the Purkinje cells.
There was no short-term memory in this rudimentary basal ganglia system. This was only created when the neurons of the matrix also found their way into the climbing fibre system of the cerebellum. The necessary double negation at the beginning, later quadruple negation and the time delay due to the relatively long distances led to the time delay and thus to the development of short-term memory.
At this point, an important difference between the ancient striatum and the later cerebral cortex should be pointed out. The cerebral cortex uses the excitatory transmitter glutamate. The striatum, however, uses the inhibitory transmitter GABA.
This means that the descending pathways from the striatum GABAerg were inhibitory. A direct and exciting control of muscles was therefore not possible. After all, GABAergic signals can only have an inhibitory effect. A pure inhibition does not trigger active muscle movement. Therefore, there must already have been a switchover of the inhibitory striate output to excitatory transmitters at this time. This switching could only occur in the nucleus ruber.
The only way to create an exciting signal from an inhibiting signal is to negate an input signal. However, to prevent the negation result from having the opposite effect, this negation had to be performed twice. In the first negation, the inhibitory, striatal output of the matrix neurons was first negated in the globus pallidus externa. This was created as an offshoot (copy) of the globus pallidus interna. For this purpose the input signal from the nucleus subthalamicus was needed. The resulting output signal was GABAerg, thus inhibiting. By negating this signal again, the desired switchover to an excitatory transmitter, glutamate, was realized. This negation took place in the nucleus ruber. This nucleus formed its own input signal necessary for negation from the excitatory, ascending input of the reticular format. The second negation took place in the nucleus ruber, otherwise not the original signal but its negation would have left the system and caused the opposite of what was actually planned.
If the output of the nucleus ruber had found a way to the cerebellum via the climbing fibres, the first short-term memory of the cerebellum would have been created.
Thus, already in primeval times - when the cortex cortex was still a distant vision - there was a matrix in the striatum which projected inhibitingly onto the globus pallidus externa, from where the output moved to the nucleus ruber and finally formed the descending trajectories, but now as an exciting signal.
Later, when the cerebral cortex was formed above the striatum, there was the excitatory, glutamatergic output from the cortex cluster instead of the previous GABAergic striatum output from the matrix cluster. Therefore, two additional negations were needed to continue using the previous system. The first was in the striatum, which now formed single signals instead of average signals. For this purpose, only the catchment areas of the already quite large dendritic fields had to be strongly enlarged again. Therefore, no mean value signals were generated, but the required single signals. At these inhibitory input signals the inhibitory input of the substantia nigra pars compacta of subtype D2 was negated. The second new negation was of the substantia nigra pars reticulata, which apparently split off from the globus pallidus externa. Therefore, today's brains of higher mammals apparently use the quadruple negation in the basal ganglia system. This became necessary with the development of the parvocellular system of the developing cerebral cortex. This development went hand in hand with the integration of the limbic system and especially the dopaminergic system of the developing substantia nigra and the system of amygdala and hippocampus. This dopaminergic system led to the development of long-term memory, as will hopefully be shown in a future monograph.
This observation teaches that the brain as such was already fully functional when the cerebral cortex did not exist. At that time, the cerebellum was already functioning as a imprintable system with magnocellular climbing fibres. The system clock of the strio-somal system was also already present, because the basic circuit elements already existed.
The parvocellular system was only added much later in the course of evolution. It is therefore theoretically conceivable that higher intelligence could also be produced without the cerebral cortex. In view of this thesis, the brain performance of living beings that were already extinct at primeval times could be reconsidered.
We summarize our findings in a new theorem:
Before the formation of the cerebral cortex, the striatum formed the outer limit of the brain. The acetylcholinergic interneurons of the striatal matrix, which received their input from the matrix of the substantia nigra, excited the GABAergic striosome neurons of the striatum. From this input, they formed a mean signal value that represented the neuronal activity in the associated matrix cluster. After the first negation of this mean value signal in the globus pallidus interna and the second negation in nucleus ruber, this signal mean value reached the climbing fibers of the cerebellum via the nucleus olivaris. A prerequisite was a sufficient strength of the mean signal so that the resulting climbing fiber signal could imprint the Purkinje cells.
The striatal output of the matrix neurons reached the globus pallidus externa as inhibitory input, where the first negation occurred. The second negation took place in nucleus ruber. From there, the excitation signal descended to the spinal cord and (after a certain stage of development of the striatal system) to the climbing fibers of the associated cerebellum cluster.
Thus, there were two climbing fiber systems in the striatum brain: the magnocellular striosomal mean system and the matrix elementary signal system. The latter was replaced in the evolutionary development of the brain by the parvocellular signal neuron system of the developing cerebral cortex and is no longer present in the brain with cerebral cortex.
(End of Theorem 2.11.)
It seems that the cholinergic projection of the matrix into the striosomes could be meaningless today. After all, the averaging for activity determination in the modern brain takes place in the cortex cortex. Nevertheless, cholinergic projection also plays a role in attention control in modern brains with a cerebral cortex.
Let's recap: The signal flow to the acetylcholinergic interneurons of the striatal matrix is via the substantia nigra. So these signals have already travelled a considerable distance. We also know that the dopaminergic projection of the substantia nigra into the striatum consists of very thin, hardly detectable and only slightly myelinated axons. Therefore, the speed of propagation of action potentials there will be relatively low.
Thus, there is a larger time difference between the glutamatergic cortex mean and the cholinergic striatum mean. The latter arrives at the striatum a few tenths of a second late. Nevertheless, it provides an activity signal. This means that neuronal activity is determined that was present several milliseconds ago. This causes an attentional coupling between the immediate present and the immediate past. A signal therefore produces a stronger climbing fiber average if a strong signal was already present immediately before. For example, a spoken syllable - interpreted as a signal - is given more attention if a syllable was perceived shortly before. This is the basis for the "binding" of syllables (phonemes) to words. In this respect, the acetylcholinergic projection of the matrix of the striatum onto the striosomes of the striatum is also helpful in modern brains and probably not atrophied for this very reason. The destruction of the cholinergic interneurons would have been an evolutionary disadvantage, which is why it apparently did not take place.
Following these considerations, a model could now be developed in which the striatum takes over the tasks of the cerebral cortex. This model could also clarify how the cerebellum actually came into being. Of course this can only be a theory, a kind of thought model. But it would be interesting to think about the basic principles according to which the evolutionary development of the nervous system took place. A prerequisite for such considerations would be to determine whether the theory presented in this monograph is useful from an initial point of view. As long as the theory presented here is completely untested, it makes no great sense to derive further, new theoretical elements from this theory. It is therefore recommended that all readers make do with what is presented here.
ISBN
978-3-00-037458-6
ISBN 978-3-00-042153-2
Monografie von Dr. rer. nat. Andreas Heinrich Malczan