Hierarchical Brain

An explanation of the human brain

First published 1st February 2024. This is version 1.5 published 2nd March 2024.
Three pages are not yet published: sleep, memory and an index.
Copyright © 2024 Email info@hierarchicalbrain.com

Warning - the conclusions of this website may be disturbing for some people without a stable mental disposition or with a religious conviction.


A synapse is a junction or connection between two neurons in the brain that allows an electrical signal in the first neuron to be transmitted to the second neuron.

Neurons and synapses are the building blocks for the workings of the brain and the obvious components for the lowest level in my hierarchy of levels of description of the workings of the human brain. It is ability of synapses to flexibly change and therefore retain a memory of past activity, along with the coincidence detection ability of neurons, that provides the basis of this hierarchy.

This page first provides a high-level description of the characteristics and capabilities of the two types of synapses, electrical and chemical; at a lower level of detail, both types also make use of the movement of ions, and chemical synapses are dependent on the action of neurotransmitters. An understanding of the lower levels is not required for my hierarchical explanation of the workings of the brain.

Contents of this page
Overview - including terminology, structure and functionality, and the requirements for the next higher level of the hierarchy.
Electrical synapses - some detail on electrical synapses.
Chemical synapse - a brief overview of chemical synapses.
A comparison of the two types - a comparison of electrical and chemical synapses.
Statistics - some numbers, sizes and other statistics about synapses.
Change over time - the changes that can take place in synapses that can cause changes to signals.
Support - the support provided to synapses by glial cells.
Conclusions - including possible reasons for why synapses so complicated.
References - references and footnotes.


Electrical synapses

Chemical synapses

A comparison of the two types


Change over time



References For information on references, see structure of this website - references

  1. ^ Autapse-induced multiple coherence resonance in single neurons and neuronal networks - Yilmaz, Ozer, Baysal and Perc 2016
    doi: 10.1038/srep30914 downloadable here or see GoogleScholar.
    First page, beginning of main text: “Autapse is an unfamiliar synapse, which happens between the axon and soma of the same neuron, and forms a time-delayed self-feedback mechanism. This special kind of synapses on the nervous system was firstly explored by Van der Loos and Glaser, and they called it as autapse, meaning the self-synapse. Thereafter, the existence of autapses in different brain regions was notified in various experimental studies by using different experimental techniques.”
  2. ^ In Search of Memory - Kandel 2006 Norton & Company USA - see GoogleScholar.
    This very readable book by the Nobel prize winner is an autobiography, history and text book all in one.
    In chapter 2, page 69:
    “[In 1955] Sanford Palay and George Palade at the Rockefeller Institute used the electron microscope to demonstrate that in the vast majority of cases, a slight space - the synaptic cleft - separates the presynaptic terminal of one cell from the dendrite of another cell. Those new images also revealed that the synapse is asymmetrical, and that the machinery for releasing chemical transmitters, discovered much later, is located only in the presynaptic cell. This explains why information in a neural circuit flows in just one direction.”
  3. ^ Electrical synapses, a personal perspective (or history) - Bennett 2000
    doi: 10.1016/S0165-0173(99)00065-X (no download available, although see GoogleScholar).
    Page 24, second column, first paragraph, under the heading “Electrical versus chemical”: “Chemical synapses are fundamentally unidirectional, but then most single synapses do not excite their postsynaptic targets in any case. Electrical synapses are fundamentally bidirectional, unless they are rectifying, and that may prove to be where they are most useful for mammals.”
  4. ^ Ibid. Electrical synapses, a personal perspective (or history)
    Page 17, under the heading “An aside on 'ephapses' and other nomenclatural niceties”: . Angelique Arvanitaki coined the term ephapse from the Greek to mean an apposition that is not quite so close as a synapse ... She used it to denote what she thought of as artificial synapses, which she made by laying one axon along side another where the 'action currents' generated during an impulse in one axon altered the excitability of the other axon. This terminology suggests that she thought synaptic transmission was electrical ... Ephapse then came to be used for incidental contacts in the nervous system, particularly where activity in one or more axons excited other axons.”
  5. ^ Ibid. Electrical synapses, a personal perspective (or history)
    Page 17, first column, second paragraph, part of the Introduction: “One does not have to have been at Oxford to define a synapse as a specialized site of functional interaction between neurons, although Sherrington and Eccles (and I) were. By this definition gap junctions form one class of electrical synapse. Another kind of electrical synapse mediates short latency inhibition of the Mauthner cell of teleost fishes and possibly mammalian cerebellar Purkinje cells; this form of electrical transmission is not mediated by gap junctions, and involves different junctional specializations... In addition, there probably are electrical interactions that occur between closely apposed cells without obvious gap junctions or specializations other than the absence of interposed glia. Whether these sites are to be considered synapses, i.e., specialized, or ephapses, i.e., incidental or accidental sites of interaction, may become clear with greater knowledge of the developmental mechanisms. Without deciding on a name one can still describe the electrical interaction, which does indeed appear to be uniquely associated with the close appositions.”
  6. ^ Principles of Neural Science - Fifth edition - Kandel et al. McGraw-Hill US 2012 - or see GoogleScholar.
    Page 178, Table 8-1 entitled “Distinguishing Properties of Electrical and Chemical Synapses” states that the distance between pre- and postsynaptic cell membranes is 4nm for electrical synapses and 20-40nm for chemical synapses.
    Page 184 under the heading “Chemical Synapses Can Amplify Signals”: “In fact, the separation between the two cells at a chemical synapse, the synaptic cleft, is usually wider (20-40 nm) than the nonsynaptic intercellular space (20 nm).”
    However, on the Wikipedia chemical synapse page, the section on relationship of chemical to electrical synapses says: “At gap junctions [electrical synapses], cells approach within about 3.5 nm of each other, rather than the 20 to 40 nm distance that separates cells at chemical synapses.”, referencing the earlier fourth edition of “Principles of Neural Science” from 2000 as well as another source from 2004.
  7. ^ Ibid. Principles of Neural Science
    Page 178, Table 8-1 entitled “Distinguishing Properties of Electrical and Chemical Synapses” states that the synaptic delay is “virtually absent” for electrical synapses and “Significant: at least 0.3ms, usually 1-5ms or longer” for chemical synapses.
    Page 185, second paragraph: “These several steps account for the synaptic delay at chemical synapses, a delay that can be as short as 0.3ms but often lasts several milliseconds.”
  8. ^ Ibid. Principles of Neural Science
    Pages 180, 2nd paragraph, under the heading “Electrical Synapses Provide Instantaneous Signal Transmission”: “At electrical synapses, the synaptic delay - the time between the presynaptic spike and the postsynaptic potential - is remarkably short. Such a short latency is not possible with chemical transmission, which requires several biochemical steps: release of a transmitter from the presynaptic neuron, diffusion of transmitter molecules to the postsynaptic cell, binding of transmitter to a specific receptor, and subsequent gating of ion channels... Only current passing directly from one cell to another can produce the near-instantaneous transmission observed at the giant motor synapse [an electrical synapse of the crayfish].”
  9. ^ Ibid. Principles of Neural Science
    Pages 180, 3rd paragraph, under the heading “Electrical Synapses Provide Instantaneous Signal Transmission”: “Another feature of electrical transmission is that the change in potential of the postsynaptic cell is directly related to the size and shape of the change in potential of the presynaptic cell. Even when a weak subthreshold depolarizing current is injected into the presynaptic neuron, some current enters the postsynaptic cell and depolarizes it. In contrast, at a chemical synapse the current in the presynaptic cell must reach the threshold for an action potential before it can release transmitter and elicit a response in the postsynaptic cell.”
  10. ^ Ibid. Principles of Neural Science
    Pages 180, end of second paragraph under the heading “Cells at an Electrical Synapse Are Connected by Gap-Junction Channels”: “The pore of the [gap junction] channel has a large diameter of approximately 1.5 nm, which permits inorganic ions and small organic molecules and experimental markers such as fluorescent dyes to pass between the two cells.”
  11. ^ Ibid. Principles of Neural Science
    Page 184, first paragraph: “Gap junctions are also important in the mammalian brain, where the synchronous firing of electrically coupled inhibitory interneurons generates synchronous, high-frequency oscillations. In addition to providing speed or synchrony in neuronal signaling, electrical synapses also can transmit metabolic signals between cells. Because gap-junction channels are relatively large and nonselective, they conduct a variety of inorganic cations and anions, including the second messenger Ca2+, and even allow moderate-sized organic compounds (less than 1,000 Da molecular weight) - such as the second messengers inositol 1,4,5-trisphosphate (IP3), cyclic adenosine monophosphate (cAMP), and even small peptides - to pass from one cell to the next.”
  12. ^ Ibid. Principles of Neural Science
    Page 184, first paragraph, under the heading “Chemical Synapses Can Amplify Signals”: “At most chemical synapses transmitter is released from specialized swellings of the axon, the presynaptic terminals, which typically contain 100 to 200 synaptic vesicles, each of which is filled with several thousand molecules of the neurotransmitter.”
  13. ^ Ibid. Principles of Neural Science
    Page 185, second paragraph, under the heading “Chemical Synapses Can Amplify Signals”: “Just one synaptic vesicle releases several thousand molecules of transmitter that together can open thousands of ion channels in the target cell. In this way a small presynaptic nerve terminal, which generates only a weak electrical current, can depolarize a large postsynaptic cell.”
  14. ^ Function of the voltage gate of gap junction channels: Selective exclusion of molecules - Qu and Dahl 2021
    doi: 10.1073/pnas.022324499 downloadable here or see GoogleScholar.
    Abstract on first page: “Gap junction channels span the membranes of two adjacent cells and allow the gated transit of molecules as large as second messengers from cell to cell. ...Gap junction channels formed by most connexins are affected by transjunctional voltage. ...the activated voltage gate preferentially restricts the passage of larger ions,... while having little effect on the electrical coupling arising from the passage of small electrolytes. Thus, a conceivable physiological role of the voltage gate is to selectively restrict the passage of large molecules between cells while allowing electrical coupling.”
  15. ^ Electrical synapses and their functional interactions with chemical synapses - Pereda 2014
    doi: 10.1038/nrn3708 downloadable here or see GoogleScholar.
    Start of conclusion, page 260: “Electrical synapses have proved to be more widespread in the mammalian brain than originally anticipated. Thus, networks of electrically and chemically coupled neurons are not restricted to invertebrates but seem to be a feature of all nervous systems. This realization emphasizes the need to further explore the functional properties of electrical synapses (of which we know significantly less than we do about chemical synapses) and their interactions with chemical synapses.”
  16. ^ Ibid. Electrical synapses and their functional interactions with chemical synapses
    Page 254, second paragraph: End of page 252: “...like their chemical counterparts, electrical synapses are highly modifiable by the action of neuromodulators such as dopamine and are capable of activity-dependent plasticity.”
  17. ^ Ibid. Electrical synapses and their functional interactions with chemical synapses
    Page 254, second paragraph: “...although chemical synapses seem to be structurally more complex and functionally dynamic, emerging evidence indicates that electrical synapses might be similarly complex, diverse and highly modifiable.”
  18. ^ Ibid. Electrical synapses and their functional interactions with chemical synapses
    Page 255, last-but-one paragraph: “...the development of neural circuits in disparate nervous systems seems to rely critically on interactions between chemical and electrical synapses, which reciprocally and dynamically regulate the emergence of these two forms of transmission.”
  19. ^ Electrical synapses: a dynamic signaling system that shapes the activity of neuronal networks - Hormuzdi, Filippov, Mitropoulou, Monyer and Bruzzone 2003
    doi: 10.1016/j.bbamem.2003.10.023 downloadable here or see GoogleScholar.
    Page 115, end of first paragraph: “...electrophysiological recordings have recently emphasized a key role for electrical synapses in synchronizing large neuronal ensembles at different frequency bands, which have been proposed to underlie a variety of cognitive processes, such as perception, memory, and learning. Electrical transmission should be viewed, therefore, as a complementary form of communication, not alternative to chemical signaling, with which it interacts.”
  20. ^ ^ Bridging the Gap - The Ubiquity and Plasticity of Electrical Synapses - Winlow, Qazzaz and Johnson 2017
    downloadable here or see GoogleScholar.
    Abstract, second bullet point and following: “ES [Electrical Synapses] are ubiquitous, found in all multicellular animals... ...ES may be modulated and exhibit plasticity in addition to promoting synergy between coupled neurons according to the strength of coupling. Strong electrical coupling promotes synchronous activity while weak coupling may desynchronise coupled neurons. Chemical synapses may modulate ES conductances and may regulate the degree of coupling between neurons. Because ES act as low pass filters, prolonged spike after-hyperpolarisations can allow them to act as inhibitory connections, but modifications of conductances can allow them to act as high pass filters and there is gathering evidence that their gain can be modulated and is activity dependent. ES may be modulated by anaesthetics at clinically relevant concentrations and volatile anaesthetics can reduce coupling between strongly electrically coupled neurons in a dose dependent manner. This may prove to be important during anaesthesia, given the ubiquity of ES in the mammalian brain.”
  21. ^ Foundations of Neuroscience - Open Edition - Henley (2021) downloadable here, Chapter 8 entitled “Synapse structure”
    Under the heading “Synapse types” and subheading “Electrical”, end of first paragraph (this text is not in the downloaded version, so must be a recent addition): “Electrical synapses play an important role in the development of the nervous system but are also present throughout the developed nervous system, although in much smaller numbers that chemical synapses.”
  22. ^ Interaction of anaesthetics with electrical synapses - Johnston, Simon and Ramon 1980
    doi: 10.1038/286498a0 (download not available, although see GoogleScholar).
    End of abstract paragraph on page 498: “The effects of anaesthetics on electrical synapses (gap-junctions or nexus) have not previously been studied. ... We report here the effects of several anaesthetics on electronic coupling between nerve cells, and show that electrical synapses are less sensitive to most anaesthetics than are chemical synapses and axonal membranes.”
  23. ^ Wikipedia article on Neurons at the end of the paragraph under the heading “Connectivity”, quoting article Do we have brain to spare? - Drachman 2005
    doi: 10.1212/01.WNL.0000166914.38327.BB (download not available, although see GoogleScholar).
    The Wikipedia article says: “It has been estimated that the brain of a three-year-old child has about 1015 synapses (1 quadrillion).” This is stated in a number of other places on the Internet, but I cannot find a definitive source for this figure. However, it seems like a reasonable estimate.
    The Drachman article, in the second sentence, says:
    “The cerebral cortex has about 0.15 quadrillion synapses - or about a trillion synapses per cubic centimeter of cortex.” 0.15 quadrillion equals 15x1013, but this is not the whole human brain, only the cerebral cortex, the outer part of the brain.
  24. ^ The interplay between neurons and glia in synapse development and plasticity - Stogsdill and Eroglu 2018
    doi: 10.1016/j.conb.2016.09.016 downloadable here or see GoogleScholar.
    Page 1, Overview: “The mammalian brain is a complex organ comprised of numerous cell types and greater than 1 x 1014 synapses.”
  25. ^ Livewired - David Eagleman, Canongate 2020
    Page 7: “...the total number of connections between the neurons in your head is in the hundred of trillions (around 0.2 quadrillion). To calibrate yourself, think of it this way: there are twenty times more connections in a cubic millimeter of cortical tissue that there are human beings on the entire planet.”
  26. ^ ^ ^ The Decade of Super-Resolution Microscopy of the Presynapse - Nosov, Kahms and Klingauf 2020
    doi: 10.3389/fnsyn.2020.00032 downloadable here or see GoogleScholar.
    Start of abstract, page 1: “The presynaptic compartment of the chemical synapse is a small, yet extremely complex structure. Considering its size, most methods of optical microscopy are not able to resolve its nanoarchitecture and dynamics. Thus, its ultrastructure could only be studied by electron microscopy. In the last decade, new methods of optical superresolution microscopy have emerged allowing the study of cellular structures and processes at the nanometer scale.”
    Page 2, under the heading “The Synapse in the Electron Microscopic Picture”: “The classical chemical synapse in the vertebrate CNS has a size of 0.5 to 2μm and can harbor between 100 and 400 SVs in boutons of hippocampal pyramidal neurons.”
  27. ^ Assembly of New Individual Excitatory Synapses: Time Course and Temporal Order of Synaptic Molecule Recruitment - Friedman, Bresler, Garner and Ziv 2000
    doi: 10.1016/S0896-6273(00)00009-X downloadable here or see GoogleScholar.
    End of summary on the first page: “...glutamatergic synapse assembly can occur within 1-2 hr after initial contact and that presynaptic differentiation may precede postsynaptic differentiation.”
    However, the conclusion on page 66 suggests that many new synapses may take longer to form than this, even where an axon is already touching a dendrite.
  28. ^ Fundamental Neuroscience ed. Squire, Bloom, Spitzer, du Lac, Ghosh and Berg - Academic Press, Elsevier, Third edition 2008 or see GoogleScholar.
    Chapter 18 “Target selection, topographic maps, and synapse formation” - Burden, O’Leary and Scheiffele
    Page 427, first paragraph, under the heading “Synapse formation in the central nervous system” and subheading “The First Contact between Axons and Their Neuronal Targets”:

    “A second important realization from imaging studies has been that the assembly of synapses occurs very rapidly. The time required from initial contact to establishment of a functional synapse is only in the range of 1-2 hours, with the formation of a presynaptic terminal occurring in only 10-20 minutes and the recruitment of postsynaptic neurotransmitter receptors lagging somewhat behind. This rapid timecourse is plausible if one considers that most synaptic components are 'ready-to-go' before contact and primarily need to be redistributed in response to a cell surface signal.”
  29. ^ Molecular mechanisms of CNS synaptogenesis - Garner, Zhai, Gundelfinger and Ziv 2002
    doi: 10.1016/S0166-2236(02)02152-5 downloadable here or see GoogleScholar.
    Page 244, second paragraph “On average, each of the 1011 neurons in the human brain receives and makes [around] 10,000 synaptic contacts. These can be excitatory, inhibitory or modulatory in nature. The vast majority is excitatory and uses glutamate as a neurotransmitter. Inhibitory neurotransmission is mediated by glycine or GABA, whereas modulatory neurotransmission is mediated by, among others, noradrenaline, 5-HT, dopamine, ACh and neuropeptides. Although presynaptic boutons from any given neuron generally release transmitter of one type, neurons usually receive multiple forms of synaptic input, which can be excitatory, inhibitory or modulatory. As such, each postsynaptic cell is able to place the appropriate complement of transmitter receptors into the PSD [postsynaptic density, an electron-dense thickening] of each synapse type”
    Figure 2 on page 245 is titled “Synaptogenesis at CNS glutamatergic synapse” and it shows four complex steps that make up the process of creating a new synapse between an axon and a dendrite. It states that all four steps can take place within approximately 90 minutes.
  30. ^ A Simple Rule for Dendritic Spine and Axonal Bouton Formation Can Account for Cortical Reorganization after Focal Retinal Lesions - Butz and van Ooyen 2013
    doi: 10.1371/journal.pcbi.1003259 downloadable here or see GoogleScholar.
    This paper is nicely summarised in a Science Daily article under the heading “Activity regulates synapse formation”: “...results show that the formation of new synapses is driven by the tendency of neurons to maintain a 'pre-set' electrical activity level. If the average electric activity falls below a certain threshold, the neurons begin to actively build new contact points. These are the basis for new synapses that deliver additional input - the neuron firing rate increases. This also works the other way round: as soon as the activity level exceeds an upper limit, the number of synaptic connections is reduced to prevent any overexcitation - the neuron firing rate falls. Similar forms of homeostasis frequently occur in nature, for example in the regulation of body temperature and blood sugar levels.”
  31. ^ The Molecular and Systems Biology of Memory - Kandel, Dudai and Mayford 2014
    doi: 10.1016/j.cell.2014.03.001 downloadable here or see GoogleScholar.
    Page 164, part 1, end of first paragraph: “...the cellular connectionist approach, which derived from Cajal’s idea that memory is stored as an anatomical change in the strength of synaptic connections (1894)... (In 1948 Konorski renamed Cajal’s idea synaptic plasticity [the ability of neurons to modulate the strength of their synapses as a result of use].)”

Page last uploaded Sat Mar 2 02:55:43 2024 MST