Neurological basics

Here we explain some basic neurological terms that are helpful for further understanding.

For the basics of genes and heredity (genes, gene expression, DNA, RNA, nucleotides, proteins, amino acids), see Building blocks of heredity and behavior: Genes, DNA, RNA, Proteins and Co

• 1. Neurons
• 2. Glial cells
  • 2.1. Astrocytes (CNS) / mantle cells (peripheral)
  • 2.2. Oligodendrocytes (CNS) / Schwann cells (peripheral)
  • 2.3. Ependymal cells
  • 2.4. Microglia
• 3. Synapses
• 4. Messenger substances: Neurotransmitters, hormones
• 5. Receptors
  • 5.1. Agonists and antagonists
  • 5.2. Constitutive activity
  • 5.3. Allosteric modulators
  • 5.4. Downregulation, upregulation, desensitization
• 6. Action potential
• 7. Blood-brain barrier
• 8. Synaptic plasticity: learning and unlearning
  • 8.1. Short-term plasticity
    • 8.1.1. Depolarization induces suppression of inhibition (DSI) or excitation (DSE)
    • 8.1.2. Metabotropic-induced suppression of inhibition (MSI) or excitation (MSE)
  • 8.2. Long-term plasticity
    • 8.2.1. Long-term potentiation (LTP)
    • 8.2.2. Long-term depression (LTD)
    • 8.2.3. Slow self inhibition (SSI)
• 9. Brain - structure and regions
  • 9.1. Spinal cord
  • 9.2. Brain stem
  • 9.3. Cerebellum
  • 9.4. Diencephalon
  • 9.5. Cerebrum (cerebral cortex, cerebrum, end brain, telencephalon)
• 10. Brain regions and functions - hardware and software
• 11. Cognition and emotion, thoughts and emotions

1. Neurons¶

Neurons are nerve cells. They consist of

• Soma (the actual cell body, perikaryon)
• Cytoplasm (consisting of the cytosol, the cell fluid, and the organelles floating in it (mitochondria, Golgi, etc.))
• the nucleus (the cell nucleus in the soma)
• many dendrites (where they receive information from other cells through tens of thousands to millions of synapses) and
• an axon (neurite) via which they send information to other cells.

While dendrites are at most a few hundred micrometres short, axons in humans can be between 0.1 millimetres and over a meter (or even up to 4 meters)¹ long. The axoplasm within the axon comprises more than 90 % of the cytosol. The axon hillock is the origin of the nerve cell’s electrical signal and connects the cell nucleus and axon. Terminals are located at the end of an axon, which transmit the information from the presynaptic cell to postsynaptic cells via chemical synapses. The axonal synapses usually dock onto dendrites, sometimes onto somata and rarely also onto axons of other cells.
Axons can have a myelin sheath made of Schwann cells. This “insulates” the electrical conduction of the axon and causes a regular amplification of the electrical signal to be passed on by means of the lacing rings where the insulation is interrupted. The thicker the axon and the better it is coated (myelinated) by glial cells (oligodentrocytes in the brain, peripheral Schwann cells), the faster the electrical transmission (up to 120 meters / second).

If enough neurotransmitters dock to the excitatory receptors of a neuron and not enough to inhibitory receptors, an action potential is triggered. The neuron fires this as an electrical impulse via the axon to the active zones at the synapses, where vesicles fuse with the cell membrane and release neurotransmitters into the synaptic cleft.
Nerve cells can fire up to 500 times/second.

The human brain has around 100 billion nerve cells.
These are:²
glutamatergic - approx. 20,000,000,000 (20 billion)
GABAergic - approx. 9,000,000,000 (8 billion)
serotonerg - approx. 250,000
dopaminergic - approx. 250,000², 400,000 to 600,000
noradrenergic - approx. 30,000 to 50,000

Information is represented by a simultaneous (rhythmic) firing of a respective group of nerve cells.

(https://media.sketchfab.com/models/b7d5d0a1996a4eddaa44a631ebff6e4f/thumbnails/b9ccaa7964d4445c868b0ef519cbfb71/a53650d6fb914ac0a02986a2f86da90b.jpeg)
Schematic drawing of a nerve cell
[Nerve cell as 3D animation at DocCheck Flexikon]
Image of an axon

Fundamental: Shadlen, Kandel (2021): Nerve Cells, Neural Circuity and Behavior. In: Kandel, Koester, Mack, Siegelbaum (2021): Principles of Neuronal Science.

2. Glial cells¶

All cells in the nervous system that are not neurons are called glial cells.
In the nervous system of vertebrates, there are 2 to 10 times as many glial cells as neurons.
Glial cells do not send signals, but support nerve cells.

2.1. Astrocytes (CNS) / mantle cells (peripheral)¶

Astrocytes nourish the neurons via contacts with blood vessels. Astrocytes are significantly involved in fluid regulation in the brain and ensure that the potassium balance is maintained.
Astrocytes (astroglia) is the name of these cells in the central nervous system. (brain / spinal cord)
These cells are called mantle cells (satellite cells) if they occur in the body (peripherally).

2.2. Oligodendrocytes (CNS) / Schwann cells (peripheral)¶

Form the myelin sheaths around axons in the CNS. In the periphery, these are called Schwann cells.

2.3. Ependymal cells¶

Form a single-cell layer (the ependyma) in the ventricles of the CNS, which separates the cerebrospinal fluid (CSF) from the brain tissue.

2.4. Microglia¶

Microglia are immune effector cells in the CNS. They only formally belong to the glial cell family. More precisely, they are cells of the mononuclear-phagocytic system.

Fundamental: Stevens, Polleux, Barres (2021): The Cells of the Nevrous System. In: Kandel, Koester, Mack, Siegelbaum (2021): Principles of Neuronal Science.

3. Synapses¶

Synapses are the junctions through which nerve cells communicate with each other.
There are

• electrical synapses, which transmit electrical signals directly and therefore very quickly, but this is only possible to smaller neurons, and
• chemical synapses in which the signal is mediated via neurotransmitters, which firstly enables modulating control and secondly amplification of the signal so that larger neurons can also be addressed.

While muscle cells are usually only excitatory controlled by a single motor neuron and each individual signal causes muscle activation, neurons in the brain are networked with each other in multiple and redundant ways, can be connected to each other in an excitatory or inhibitory manner and require the interaction of many signals (often 50 to 100) for activation.

Fundamental to this is Yuste, Siegelbaum (2021): Synaptic Integration in the Central Nervous System. In: Kandel, Koester, Mack, Siegelbaum (2021): Principles of Neuronal Science.

Symmetrical synapse (type II synapse)³

• rather inhibitory effect
  • mostly GABAergic
• flattened vesicles
• less pronounced active zone
• rather narrow synaptic cleft
• pre- and postsynaptic zone about the same thickness
• mostly near the soma (axodendritic, axosomatic, axoaxonal)

Asymmetric synapse (type I synapse)³

• rather excitatory effect
  • mostly glutamatergic
• round vesicles
• wide active zone
• wide synaptic cleft
• postsynaptic apparatus (postsynaptic density)
• is strongly pronounced, it is called an asymmetrical synapse (also type I synapse)
• mostly axo-spinal

4. Messenger substances: Neurotransmitters, hormones¶

Neurotransmitters are messenger substances that transmit information at chemical synapses between nerves. Examples are dopamine, noradrenaline, serotonin, acetylcholine, GABA and glutamate. The different neurotransmitters have different tasks in the brain and overlap in their effects.
The release of neurotransmitters at the synapses causes chemical stimulus transmission or blockade between neurons (nerve cells).
Other messenger substances, the hormones, slowly transmit their effect via the bloodstream to more distant target organs (e.g. adrenaline, cortisol, estradiol, insulin, testosterone, thyroxine, triiodothyronine).
Some substances act as both neurotransmitters and hormones (e.g. noradrenaline, serotonin, histamine) and some substances act as both neurotransmitters and hormones (e.g. noradrenaline, serotonin, histamine).

Neurotransmitters are usually synthesized in the cytosol of the cell nucleus, packaged in vesicles and transported via the microtubules through the axons to the nerve terminals where the transmitting synapses are located. The transport speed in the axons varies depending on the substance and is up to 5 µm/second = approx. 40 cm/day.⁴ Some neurotransmitters are only synthesized on demand at the axon terminals (e.g. endocannabinoids).
The release of neurotransmitters is triggered by an increase in intracellular Ca2+. The intracellular Ca2+ increase is caused by a depolarization of the presynaptic nerve terminals and an influx of Ca2+ via voltage-dependent Ca2+ channels (VDCCs).⁵
In response to the action potential, the neurotransmitters are released from the nerve terminals into the synaptic cleft as the vesicles connect with the membrane. The synaptic cleft is between 20 and 40 nm wide.⁶
In the synaptic cleft, they dock onto postsynaptic (rarely also “retrogradely” onto presynaptic, such as endocannabinoids and nitric oxide) receptors and thereby open ion channels, which can trigger a new action potential in the receiving cell.
The neurotransmitters then detach from the postsynaptic receptors and are reabsorbed into the transmitting cell in or at the edge of the synaptic cleft by presynaptic transporters. In the cell, they are either stored again in vesicles until the next release, or metabolized by degrading enzymes (e.g. dopamine and noradrenaline by monoamine oxidase and COMT).
Neurotransmitters that are not reabsorbed diffuse into the extracellular space and can trigger autoreceptors of the sending cell or receptors or transporters of other cells from there.

The purpose of chemical signal transmission by neurotransmitters is the filtering and modulation of signals and the possibility of amplifying the signal to be transmitted.

Depending on the receptor to which they dock, neurotransmitters have an excitatory (activating) or inhibitory (inhibiting) effect on the subsequent nerve cell. Although dopamine and serotonin are predominantly involved in the transmission of inhibitory information, only the D2, D3 and D4 receptors have an inhibitory effect (they inhibit the enzyme adenylyl cyclase), while the D1 and D5 receptors have an activating (excitatory) effect (they activate the enzyme adenylyl cyclase).

In ADHD, the transmission of information in the brain is primarily impaired in relation to the neurotransmitters dopamine and noradrenaline.

5. Receptors¶

Receptors are receiving docking sites for messenger substances. Depending on the receptor, a messenger substance can have an inhibiting or activating effect.

Ionotropic receptors
In these, the binding of a neurotransmitter directly causes the opening of an ion channel.

Metabotropic receptors
In these, the binding of a neurotransmitter causes the activation of messenger substances (second messengers), which in turn can address a number of transport channels.
All dopamine and noradrenaline receptors are metabotropic.

Fundamental to this Siegelbaum, Clapham, Marker (2021): Modulation of Synaptic Transmission and Neuronal Excitability: Second Messengers. In: Kandel, Koester, Mack, Siegelbaum (2021): Principles of Neuronal Science.

Excitatory and inhibitory receptors.
Receptors for one and the same neurotransmitter can have an excitatory (increasing the postsynaptic nerve voltage) and inhibitory (decreasing the postsynaptic nerve voltage) effect.
In contrast, neither the firing of neurons nor the type of neurotransmitter say anything about whether a signal should be activating (excitatory) or inhibiting (inhibitory).

5.1. Agonists and antagonists¶

Ligands are substances that bind to receptors.
Biased ligands are ligands that trigger signaling in receptors only via specific signaling pathways. G protein-coupled receptors mediate their signal via various G proteins (GTPases; 20 trimeric and more than a hundred “small” G proteins). Biased ligands only trigger individual G-protein signaling pathways.

Agonist: Binding to the receptor activates it and triggers the receptor signal.
Conventional agonist: increases the proportion of activated receptors.

Partial agonist / partial agonist: less effective agonist.
Some agonists act as partial agonists in one tissue and as complete agonists in another tissue.

Inverse agonist: Binds to spontaneously active receptor and reduces its activity. Example: antihistamines.
Spontaneously active are receptors that send signals even without a stimulus.

Antagonist: binds to receptor without any effect of its own. Prevents receptor activation by other substances.
Antagonists that block the effects of a substance that normally reduces cellular function increase cellular function.
Antagonists that block the effects of a substance that normally increases cellular function reduce cellular function.

Reversible antagonist: easily detaches from the receptor after binding to it.
Irreversible antagonist: no longer detaches from the receptor because it forms a stable, permanent or almost permanent chemical compound (e.g. in the case of alkylation).
Pseudoirreversible antagonist: slowly dissociates from its receptor.

Competitive antagonist: prevents the binding of an agonist to the receptor.
Non-competitive antagonist: can bind agonist and antagonist simultaneously. The binding of the antagonist reduces or prevents the effect of the agonist.
Reversible competitive antagonist: Agonist and antagonist form short-term bonds with the receptor. An equilibrium is established between agonist and antagonist at the receptor.
An increase in the concentration of the agonist can overcome reversible competitive antagonism.
Example: The opioid receptor antagonist naloxone, given shortly before the agonist morphine, blocks the effect of the agonist morphine. An increase in the agonist morphine can overcome the competitive antagonism by naloxone.
Irreversible antagonism is a subset of non-competitive antagonism.

Neutral antagonist: has the same affinity for the active and inactive receptor state and does not interfere with the basal activity of the cell.

Agonist-antagonist: acts as an agonist and antagonist at the same time
Structural analogs of agonists often exhibit this property.
Example: Pentazocine activates opioid receptors and at the same time blocks their activation by other opioids. As a result, pentazocine itself has an opioidergic effect, but weakens the effect of other opioids as long as it is still bound.

G protein-coupled receptors can have different conformational states depending on the ligand binding to them.¹³

5.2. Constitutive activity¶

A receptor does not always require an agonist to enter an active conformational state that maintains elevated baseline levels of intracellular signaling.
Numerous GPC receptors (e.g. the CB1R) show a high degree of constitutive activity.
The two-state model of receptor activation explains this:
Receptors are in equilibrium between the active and inactive states. An agonist stabilizes the active state that leads to activation, a neutral antagonist binds equally to active and inactive states, while an inverse agonist preferentially stabilizes the inactive state.

5.3. Allosteric modulators¶

Receptors can have different binding sites. Agonists (activate receptor) and antagonists (inhibit receptor) bind to the orthosteric binding site. Modulators can bind to the allosteric binding site, which can increase or decrease the effect of the receptor if an agonist binds to it.
An allosteric modulator thus alters the effects of an orthosteric ligand (e.g. an agonist or inverse agonist) on a target protein (usually a receptor) by binding to a different (allosteric) binding site than the orthosteric agonist binding site. This causes a conformational change in the receptor protein, which alters the receptor affinity or efficacy of the orthosteric ligand.

Positive allosteric modulator (PAM): enhances the effect of an agonist or inverse agonist.
Negative allosteric modulator (NAM): attenuates the effect of an agonist or inverse agonist without having an effect itself.
Silent modulator (SAM): Occupies the allosteric binding site without influencing the effect of agonists or inverse agonists.

Allosteric agonist: Activates receptor in the absence of an orthosteric ligand via binding to an allosteric binding site
Ago-allosteric modulator: acts as an allosteric agonist (activator) as well as an allosteric modulator. Example: Injection narcotics barbiturates

On-target allosterization: modulator binds to the same protein as the orthosteric ligand
Off-target allosterization: Modulator binds to a partner protein. Example: GPCR oligomers.

5.4. Downregulation, upregulation, desensitization¶

The receptors for dopamine, noradrenaline, cannabinoids, adenosine, serotonin and opioids, among others, are members of the GPCR family. GPCRs are often subject to dynamic changes in their activity.
A lack of agonists can lead to upregulation
A prolonged excess of agonists can cause desensitization and downregulation¹⁴
Agonists can trigger time- and temperature-dependent endocytosis (internalization). During endocytosis, some receptor proteins are reintegrated into the cell membrane (recycling), while others are sorted out and degraded by lysosomes, which reduces the number of receptors.¹⁵¹⁶

Homologous desensitization
The receptor that has bound a ligand is phosphorylated by a kinase (G-protein-coupled receptor kinase, GRK). This phosphorylation stabilizes the binding between the receptor and arrestins. This prevents interaction with the G protein and interrupts signal transduction.

Heterologous desensitization
The signaling chain of a receptor is interrupted or reduced (independent of ligand binding) due to activation of other receptors on the cell surface. The activated receptors activate via second messenger kinases (e.g. protein kinase A, protein kinase C), which do not phosphorylate the activated receptor itself, but other receptors.

6. Action potential¶

Neurons transmit signals by triggering an action potential.
In their resting state, neurons contain an average voltage of 65 mV (between 45 and 90 mV depending on the cell type) lower than the extracellular space. This voltage difference is created by the so-called sodium-potassium pump (sodium-potassium ATPase, a membrane protein), which exchanges sodium ions from the inside of the cell for potassium ions from the extracellular space. Through potassium-permeable ion channels in the self-impermeable cell membrane, the potassium ions - following the concentration gradient - can slowly leave the cell again, leaving behind a non-neutralized negative charge on the inner cell membrane surface, which is usually around -65 mV.
At rest, the cells then contain around 1/10 as many sodium ions and 20 times as many potassium ions as extracellularly. The extracellular sodium and potassium ion level is maintained by the kidneys and the astrocytes. If sodium or calcium ions enter the cell, its voltage increases.
An action potential (a rapid voltage increase of +10 mV, e.g. from -65 to -55 mV) makes the cell membrane more permeable to sodium ions than to potassium ions. The resulting increased entry of sodium ions further increases the cell wall permeability for sodium ions, so that more and more sodium ions enter. This causes the negative voltage to drop abruptly and even briefly (for around 1 ms) turn positive to + 40 mV (“overshoot”). The action potential now travels at 1 to 100 meters/second along the axon to the terminals, where it opens ion channels.

The action potential is an all-or-nothing decision. If it is triggered, it always has full strength, regardless of whether the trigger threshold is only just exceeded or greatly exceeded.
The action potential remains constant over the entire distance in the axon. For this purpose, it is amplified at the Ranvier cords.

After the voltage maximum is reached, the return to the resting potential (repolarization) takes place through the closing of sodium channels and the opening of potassium channels.
The membrane voltage initially becomes even more negative than the original resting potential (hyperpolarization). The cell then returns to the starting point (resting potential).
After the triggering of an action potential, a neuron undergoes a pause, the refraction period.

Phases of the action potential:¹⁷

• Initiation phase
  • Voltage increases (slowly or quickly) towards the threshold potential, e.g. from -70 mV to -50 mV (initial depolarization)
  • If incoming stimuli (after summation in the axon hillock) do not reach the threshold value, there is a temporary, reversible change in the membrane potential
• Spread
  • Complete depolarization only occurs when the threshold potential is reached
  • Consequences:
    • The voltage-dependent sodium channels open and suddenly allow Na+ ions to flow from the extracellular space into the cytosol of the neuron
    • Meanwhile, the potassium channels are closed
    • A positive feedback mechanism even causes a charge reversal (“overshoot”) at the end.
• Repolarization
  • Sodium channels begin to close again before the potential peak
  • The voltage-dependent potassium channels open, allowing K+ ions to flow from the inside of the cell into the extracellular space
  • The conductivity of the potassium channels reaches its maximum when almost all sodium channels are already inactivated
  • During repolarization, the potential moves back towards the resting potential, which leads to the closure of the potassium channels, while the sodium channels are slowly reactivated.
• Hyperpolarization
  • Potassium channels close within 1 to 2 ms, and therefore more slowly than sodium channels
  • Meanwhile, the membrane potential drops below the actual resting potential (“hyperpolarization”)
• Refractory period
  • after an action potential, the neuron is not excitable for a short time
  • until the sodium channels can be reactivated
  • Absolute refractory phase: Period shortly after overshoot, before repolarization is completed. Action potential cannot be triggered.
  • Relative refractory phase: threshold value for triggering an action potential is increased

While the action potential is always equally strong and is the only outgoing impulse of a neuron, there are two types of activating impulses:

• the synaptic signal
• the receptor signal.
  Both are graduated in terms of strength.

Receptor signals are triggered by peripheral sensory stimuli, for example. A receptor signal corresponds in duration and strength to the intensity of the stimulus, but is relatively weak overall. It only reaches a few millimeters within the neuron. After one millimeter, it has already lost two thirds of its energy. If it reaches a Ranvier ring with sufficient strength within its range, its amplification effect triggers a complete action potential so that the sensory stimulus can reach the spinal cord.

Synaptic signals are triggered by neurotransmitter binding at receiving synapses on dendrites. Like the receptor signal, they are gradual depending on the number of activated receptors. Synaptic signals are summed at the axon hillock of the neuron. If the sum exceeds the threshold value, the action potential is triggered.

Even if an action potential is always equally strong, it can cause a gradually graded release of neurotransmitters due to the frequency and rate of its sequence and thus transmit signals of different strengths to the postsynaptically connected cells. If an action potential is only triggered once. The more frequently and quickly the action potential is triggered in succession, the greater the amount of transmitter release, which leads to a higher number of postsynaptically addressed receptors.

Fundamental on this Koester, Siegelbaum (2021): Membrane Potential and the Passive Electrical Properties of the Neuron. In: Kandel, Koester, Mack, Siegelbaum (2021): Principles of Neuronal Science and Bean, Koester (2021): Propagated Signaling: The Action Potential. In: Kandel, Koester, Mack, Siegelbaum (2021): Principles of Neuronal Science.

7. Blood-brain barrier¶

Around 600 km of blood vessels run through the human brain.
Blood vessels in the brain have special cells in their walls that prevent certain substances that are harmless in the body (peripheral) from interfering with the complex and sensitive processes of the brain (central) and prevent neurotransmitters and potassium from leaking from the extracellular cerebrospinal fluid into the blood.
Only fat-soluble substances with a molecular weight below 500 Da can diffuse through the blood-brain barrier, such as nicotine, alcohol, blood gases or narcotics such as halothane, but not ions or polar substances such as glucose. The latter are dependent on specific transport systems, which thus perform a regulatory and filtering function¹⁸

8. Synaptic plasticity: learning and unlearning¶

Synaptic plasticity refers to the brain’s ability to create new connections between nerve cells, representing knowledge and experience, and to remove them again. Synaptic plasticity also involves increasing or decreasing the activity and stability of firing.
Different types of synaptic plasticity are:

• Short-term plasticity: change in synaptic activity over milliseconds to seconds
• Long-term plasticity: change in synaptic activity over hours, days or longer
• Structural plasticity: change in the number and organization of synapses
• Functional plasticity: changes in the release and modulation of transmitter substances
• Presynaptic plasticity: adaptive mechanisms for modulating synaptic transmission at the presynapse

8.1. Short-term plasticity¶

8.1.1. Depolarization induces suppression of inhibition (DSI) or excitation (DSE)¶

Depolarization caused by strong activation (repeated action potential or a step depolarization) induces a transient suppression of inhibition (DSI) or excitation (DSE) in many neurons.¹⁹
This inhibition suppression lasts for a few dozen seconds.
Inhibitory synapses are more sensitive to depolarization-induced suppression of synaptic transmission than excitatory synapses.
DSE is dependent on a functioning endocannabinoid transporter.²⁰

8.1.2. Metabotropic-induced suppression of inhibition (MSI) or excitation (MSE)¶

Metabotropic (by means of a metabolic process) induced suppression of inhibition (MSI) or excitation (MSE) are forms of short-term synaptic plasticity¹⁹

MSI and MSE are triggered by a variety of Gq/11-coupled GPCRs, including mGluR1, mGluR5, M1, M3, OrexinA, CCKA and α1-adrenergic receptors.

8.2. Long-term plasticity¶

8.2.1. Long-term potentiation (LTP)¶

Long-term potentiation (LTP) is a universal form of long-lasting strengthening of synaptic connections.
LTP can be caused by

• increased formation of action potentials
• improved communication between two cells
• Enlargement of the synapses
• Creation of new channels
• Increased release of neurotransmitters

8.2.2. Long-term depression (LTD)¶

Long-term depression (LTD) is a universal form of prolonged reduction in synaptic connections that lasts for tens of minutes to several hours or longer²¹
Homosynaptic LTD: only affects the synapse that is reached by the sustained low-frequency activity of the presynaptic neuron. Particularly affects glutamatergic synapses in the dorsal and ventral striatum¹⁹
Heterosynaptic LTD: also affects inactive neurons. The signal attenuation is controlled by an adjacent modulating interneuron and is not dependent on the activity of the presynaptic or postsynaptic neuron. For example, stimulation of Schaffer collaterals in CA1 of the hippocampus causes a sustained decrease in GABA-ergic inhibition of CA1 pyramidal neurons.¹⁹
Autaptic LTD: autaptic neurons exhibit both endocannabinoid-mediated DSE and MSE. Autaptic LTD is dependent on CB1R, whereby autaptic LTD is not induced via the G(i/o) or G(s) proteins typically activated by CB1R, but via G(q) proteins.²¹

8.2.3. Slow self inhibition (SSI)¶

Slow self-inhibition (SSI) is a process that suppresses neuronal excitability. SSI occurs mainly in low-threshold spiking cortical interneurons and cerebellar basket cells, but also in some main cortical cells.¹⁹

9. Brain - structure and regions¶

In the course of evolution, different areas of the brain have gradually developed, which we present below from old to new.
Fundamental to the areas of the human brain: Kandel, Shadlen (2021): The Brain and Behavior. In: Kandel, Koester, Mack, Siegelbaum (2021): Principles of Neuronal Science.

9.1. Spinal cord¶

The spinal cord receives and processes sensory, peripheral stimuli. Counts as part of the CNS.

9.2. Brain stem¶

• evolutionary oldest part of the brain
• connects and processes incoming sensory impressions and outgoing motor information
• responsible for elementary and reflex control mechanisms
• lowest brain area, directly on the spinal cord
• consisting of
  • Midbrain (mesencephalon)
  • Bridge (Pons)
  • Medulla oblongata (medulla oblongata; hindbrain)
    • the hemispheric nerve tracts cross here
    • controls many automatic processes such as
      • Heartbeat
      • Breathing
      • Metabolism
      • Reflex centers, e.g. for
        • Eyelid closure
        • Swallowing
        • Cough

The brain stem as a 3D animation at dasGehirn.info
The mesencephalon as a 3D animation at dasGehirn.info
The medulla oblongata as a 3D animation at dasGehirn.info

9.3. Cerebellum¶

Distinguishes between two hemispheres
Responsible for

• Balance
• Movements
• Movement coordination
• unconscious learning
  • Language acquisition
  • social learning

The cerebellum as a 3D animation at dasGehirn.info

9.4. Diencephalon¶

The diencephalon is involved in

• Sleep-wake control (see ARAS, pain perception, temperature regulation).

The diencephalon consists of:

Thalamus (upper part)

• transmits sensory and motor signals to and from the cerebrum
• collects all the information from the sensory organs and passes it on
• consists mainly of gray matter

Hypothalamus

• controls numerous physical and mental life processes
• is partly controlled neuronally via the autonomic nervous system, partly hormonally via the bloodstream
• associated with the pituitary gland (hypophysis)

The hypothalamus and pituitary gland are the central link between the endocrine and nervous systems.

Subthalamus (thalamus centralis)

• consisting of
  • Subthalamic nucleus
  • Pallidum (not to be confused with globus pallidus)
• Control of gross motor skills

Epithalamus

• consisting of
  • Pineal gland (pineal gland, pineal corpus, pineal gland)
  • Subcommissural organ (Organum subcommissurale)
  • Commissura habenularum
  • Commissura posterior (Commissura epithalamica)
  • Habenulae (reins)
  • Area pretectalis

The diencephalon as a 3D animation at dasGehirn.info.

9.5. Cerebrum (cerebral cortex, cerebrum, end brain, telencephalon)¶

Parts of the cerebrum are:

Cerebral cortex (cortex cerebri)²²

• Surface layer of the cerebrum
• 2-4 mm thick
• heavily folded (like a cloth in a glass)
• just under a quarter of a square meter in size
• contains around 16²³ or 19 (for women) to 23 billion for men²⁴(ca. 20 % des gesamten Gehirns)
• Cell layers depending on developmental age²⁵
  • Allocortex (older; e.g. hippocampus): 3 layers. From outside to inside:
    • Archicortex
      • Molecular layer (lamina molecularis)
      • Pyramidal cell layer (lamina pyramidalis)
      • polymorphic layer (lamina multiformis)
    • Paleocortex
      • three to five cell layers
      • processes mainly smell and taste
  • Mesocortex
    • Intermediate form of allocortex and isocortex
    • three to six layers
    • is located in the insula, cingulum and parahippocampal gyrus
  • Isocortex (younger, neocortex; 90 % of the human cortex): 6 layers. From outside to inside:
    • Molecular layer (lamina molecularis)
    • Outer granular cell layer (lamina granularis externa)
    • Outer pyramidal cell layer (lamina pyramidalis externa)
    • Inner granule cell layer (lamina granularis interna)
    • Inner pyramidal cell layer (lamina pyramidalis interna)
    • polymorphic layer (lamina multiformis)
• is divided into two hemispheres (hemispheres)
  • each hemisphere is divided into 4 cerebral cortex lobes
    • frontal (PFC)
      • higher cognitive processes
      • Control of voluntary motor skills, attention, short-term memory tasks, motivation and planning
    • parietal (parietal lobe, parietal lobe, top)
      • somatosensory functions
      • visual control of movements and recognition of stimuli in the room
      • spatial thinking and “quasi-spatial” processes such as arithmetic and reading
      • Language processing
      • Interface between the sensory systems (especially the visual system) and the motor system for the calculation, execution and control of hand and eye movements.
    • occipital (back)
      • visual cortex (visual processing)
    • temporal (lateral lobe)
      • auditory cortex (acoustic processing)
      • Interpretation of information according to visual memory and language comprehension

The cerebral cortex as a 3D animation at dasGehirn.info

Corpus callosum (bar)

• thick nerve cord
• connects the two hemispheres

The corpus callosum as a 3D animation at dasGehirn.info

Cingulate gyrus

• lies dorsal to the corpus callosum
• Emotion
• Sensation of pain
• Cognition

Insula

• Emotion
• Homeostasis
• Taste sensation

The insula as a 3D animation at dasGehirn.info

Basal ganglia

• consisting of
  • dorsal striatum
    • Caudate nucleus
    • Capsula interna (in adulthood)
    • Putamen
  • Globus pallidus (not to be confused with pallidum)
    • together with substantia nigra pars reticularis forms the most important starting point of the basal ganglia
• regulates
  • Execution of movement
  • implicit memory
    • motor learning
    • Habit learning

The basal ganglia as a 3D animation at dasGehirn.info

Hippocampus

• regulates the explicit memory
  • Memory for people, places, things, events

The hippocampus as a 3D animation at dasGehirn.info

Amygdala

• coordinates the autonomic and endocrine response to emotional states
• including the fear memory (part of the implicit memory)

The amygdala as a 3D animation at dasGehirn.info.

Further anatomical distinctions can be made:

White substance

• the myelin-containing nerve fibers
• run underneath the bark

Gray matter

• Accumulations of neurons
  • pink in the living brain
  • gray in the dead brain

The limbic system as a 3D animation at dasGehirn.info

10. Brain regions and functions - hardware and software¶

Although individual brain regions have preferred functions, there is no clear 1:1 allocation.
Simple reflexes are still controlled quite clearly by specific brain regions. The more complex a behavioral function is, the more the interaction of several brain regions is used - this is referred to as brain networks.
It helps an individual to survive if important functions can be controlled alternatively by different brain regions (redundancy). Functions that are lost (e.g. if a brain region is damaged by a stroke) can therefore be taken over by other brain regions (flexibility).
Without the control of the impaired function being taken over by another brain region, it would be possible to compensate for the deterioration or total loss of a function by shifting survival strategies to increased use of other abilities (behavioral change). However, it is much easier to maintain a behavior that has already been successfully learned by maintaining important functions because they are represented by more than just one brain region and only the control of the function has to be relearned.

This also explains the difficulties in attributing certain functional impairments to defects in specific brain regions. This applies in particular to mechanisms that do not represent a specific bodily function.
The problems that exist in ADHD tend to concern mechanisms for the long-term regulation of behavior and cannot be attributed to specific hardware defects in individual brain regions.

11. Cognition and emotion, thoughts and emotions¶

An analytical understanding of the environment helps us to create a schematic image of it. We can not only imagine the elements that make up the environment, but also the mechanisms of how these elements interact and influence each other, and store them in our memory.
The ability to abstract and simplify (combining elements into groups with common properties and interaction mechanisms into common rules) allows us to store much more information and make predictions about possible relationships that we have not yet experienced ourselves in a specific individual example. This means that it is not necessary to have seen every existing snake species once in order to recognize them. It is enough to know the characteristics of snakes (elongated, no legs, often in the forest or field, usually on the ground) to recognize unknown snakes as such. It is also enough to know the venomousness of some of them to be able to deduce a risk from a snake species that has never been seen before.

Cognition and analysis are processed in the brain by the youngest brain region, the prefrontal cortex (PFC). Its analytical view of the world can perhaps be compared to looking through a microscope. This view reveals a vast amount of detail that allows many more conclusions to be drawn than without this magnification.
However, such a detailed view is only of very limited use for controlling one’s own behavior. Controlling one’s entire life through constant analysis would be far too time-consuming. There would be far too much data to evaluate at the same time. As valuable as a microscope is for looking at details, it would be overwhelming to look at all the information at the same time, for example during a social evening in a pub.

If the PFC were to control all actions itself, it would be completely overloaded. To avoid this, we store cognitively learned information (knowledge) and actions performed consciously (under the control of the PFC) in automatisms. To form a habit, an action usually needs to be practiced for 4 to 6 weeks. Through practicing and automatization, the control of the action is transferred from the PFC to other, posterior, regions of the brain. Once a habit has been formed, once an action has been automated, the PFC can devote itself to other tasks and create new knowledge.
However, automatisms and habits are not free from all control. However, their control is far less difficult and detailed. This control mechanism is our emotions. Emotions react very quickly, but also very coarsely. Emotions steer the individual subconsciously towards safe areas.
If emotions become stronger, e.g. because something particularly pleasant or problematic happens, they become perceptible. Feelings (the physical perception of emotions) report the emotions to the conscious mind and create the possibility of cognitive influence.
The better the automatisms are trained, the more conscious corrections and expansions they have undergone, the better they can meet the demands placed on the individual. People who have spent many years dealing with a certain area of life, who have practiced for a long time and have repeatedly checked the results of their emotionally driven (hypothetical or executed) actions through the microscope of the PFC and made corrections to improve the results, have very well-trained automatisms in this area - a sharpened intuition. Specialists in demanding professions (doctors, technicians, lawyers, mathematicians) are very familiar with being asked to assess something and having the feeling: “According to the known rules, it should work like this. But something is wrong here…” Without being able to immediately explain what it is. Only after some cognitive, analytical engagement with the matter do they realize what special feature is present that requires a deviation from the general rules.

Automation is the result of tightly formed synaptic connections. Cells that fire together, wire together. Joint firing is initially controlled cognitively. If it takes place long enough, the active brain neurons connect with each other so that they require less cognitive guidance to fire together.
The establishment of synaptic connections between neurons and their joint firing is promoted by LTP (long-term potentiation). LTP is the neuronal correlate of learning. LTD (long-term depression), on the other hand, helps to break habits and stop automatisms (roughly speaking: forgetting) - by weakening connections between neurons and inhibiting their joint firing.