Although synapses differ in properties, all synapses operate by the same principle.
— Sir Bernard Katz

I. Synapse

  1. Major neurotransmitters

  2. The molecular machinery for neurotransmitter release

    • Synaptic transmission is rapid = 1-5 ms.

    • Major processes govern neurotransmitter release:

      1. Synaptic vesicle fusion.
      2. Ca2+-triggering of fusion.
      3. Localized Ca2+-influx.

    • Synaptobrevin/VAMP, SNAP-25, and syntaxin form a complex, known as SNARE complex [Montecucco lab, 1992 | J. Rothman lab, 1993]; Munc18 binds to SNAREs and is homologous to Unc18 and Sec1p [Südhof Lab, 1993]; Complexins [Südhof Lab, 1995]

    • scaffolding proteins Rab3-interacting molecules (RIMs) and RIM-binding proteins (RIM-BPs): the organizers of calcium-channels in the presynaptic active zone. [Südhof Lab, 2002]

    • Synaptotagmins: Synaptotagmin-1 [Südhof Lab, 1987 | Südhof Lab, 1991] is essential for Ca2+-triggered neurotransmitter release.

      • synaptotagmin isoforms class I (Syt1, 2, 7 and 9);
      • synaptotagmin isoforms class II (Syt3, 5, 6 and 10);

    • Review: “The synaptic vesicle cycle” [By Thomas C. Südhof, Citation: 5707 (2004-2025) | DOI Link]

  3. Postsynatic receptors

    • Glutamate receptors:

    • GABA receptors:

      • GABAA: These are ionotropic (ligand-gated ion channels) and are the most abundant inhibitory receptors in the brain.
      • GABAB: These are metabotropic (G-protein-coupled receptors). They are indirectly linked to ion channels and modulate neurotransmitter release and neuronal excitability through intracellular mechanisms.

    • Dopamine receptors:

      • D1-like
      • D2-like

    • Nicotinic acetylcholine receptors (nAChR):

    • Serotonin receptors:

    • Cannabinoid receptors: CB1R

    • Opioid receptors: [[μOR] | [δOR] | [κOR] | nociceptin receptor (NOPR)]

    • Histamine receptors: [H1R | H2R | H3R | H4R]

    • Glycine receptors

    • Trafficking of postsynaptic receptors

  4. The assembly of postsynaptic density

  5. Synapse formation and Regulation of synaptogenesis

    • Identification of synaptic adhesion molecules (SAMs): Neurexin Complexes [Südhof Lab, 1992]; Latrophilin Complexes [Südhof Lab, 1998]
    • Complex that bridges the synapse: β-neurexin 1; cerebellin 1(Cbln1) [Yuzaki Lab]; GluD2

  6. Open questions

    • How calcium-channels are recruited to active zones ?
    • What mediates the calcium-triggered release that remains in synapses which lack fast synaptotagmin calcium-sensor isoforms ?
    • How synapses are formed ?
    • What signal transduction pathways organize synapse formation ? Although some of the extracellular interactions involved in synapse formation has been revealed, for example, synaptic adhesion molecules (SAMs), the intracellular signaling event is largely unknown.
    • How ePSD and iPSD is formed in single neurons ?

II. learning and memory

The idea that memory is stored in the brain as physical alterations goes back at least as far as Plato, but further conceptualization of this idea had to wait until the 20th century when two guiding theories were presented: Richard Semon’s “engram theory” developed in the early 20th century, and Donald Hebb’s “synaptic plasticity theory” in 1949.

  1. Cells that store memory in the brain:

    • Memory engram cells

  2. Cells that constitute a positioning system in the brain:

    • Place cells:
    • Grid cells:
    • Head direction cells:
    • Boundary cells: Boundary vector cells (BVCs)
    • Speed cells

III. The regulation of sleep homeostasis

  • Phosphorylation based theory

IV. The molecular architecture of sensory system

“The role of our brain is to create an internal representation of the outside world, and the senses are its principal conduit.”
— Charles S. Zuker

  1. Sense of Taste

    • Bitter taste: [TAS2R14]

  2. Sense of Smell

  3. Sense of Sight (Vision)

  4. Hearing

  5. Touch

  6. Temperature

    • TRPV1
    • TRPM8

V. The architectures of neuronal circuits

“Neurons that fire together, wire together.”
— Hebbian theory

  • Key technology: Optogenetics []

  • Mapping the Projectome

  • Axon guidance: [Netrins | Slits | Semaphorins | Ephrins]

  • Basic circuit wiring diagrams:

    • Reward circuits

  • Molecular mechanisms underlying precise axon path finding:

  • Circuit assembly during development

  • Molecular mechanisms underlying neuronal wiring specificity

Ref. Labs

learning and memory
  1. Susumu Tonegawa, MIT
  • Discovery of Memory engram cells
    • Liu X., Ramirez, S., Pang, P., Puryear, C., Govindarajan, A., Deisseroth, K., and Tonegawa S. Optogenetic stimulation of a hippocampal engram activates fear memory recall. Nature 484: 381–385 (2012). [PDF | PMID: 22441246 | DOI Link]
Sense of taste
  1. Charles S. Zuker, Columbia University
  • Discovery of Taste receptors
    • Adler E, Hoon MA, Mueller KL, Chandrashekar J, Ryba NJ, Zuker CS (2000). A novel family of mammalian taste receptors. Cell 100: 693-702. [PDF | PMID: 10761934 | DOI Link]
  1. Solomon H. Snyder, John hopkins
  • Discovery of Opioid receptors
    • Pert, Candace B., and Solomon H. Snyder. “Opiate receptor: demonstration in nervous tissue.” Science 179.4077 (1973): 1011-1014. [PDF | PMID: 4687585 | DOI Link]
  1. Lily Yeh Jan, UCSF
  • Discovery of Potassium ion channel-Shaker
    • Tempel, Bruce L., et al. “Sequence of a probable potassium channel component encoded at Shaker locus of Drosophila.” Science 237.4816 (1987): 770-775. [PDF | PMID: 2441471 | DOI Link]
Regulation of Sleep homeostasis
  1. Masashi Yanagisawa, UTSW/University of Tsukuba

Textbooks

  • Principles Of Neurobiology, Liqun Luo neurotextbook

Online Courses

  1. Synapses, neurons, and the brain, Hebrew University of Jerusalem [Coursera]

Nobel laureates

nobelxqhemox

  • David Julius, University of California, San Francisco, CA, USA
    Nobel Prize in Physiology or Medicine 2021
    From peppers to peppermints: insights into thermosensation and pain [Nobel Lecture video | Read the Lecture | Source]

  • Ardem Patapoutian, Scripps Research, La Jolla, CA, USA; Howard Hughes Medical Institute, USA
    Nobel Prize in Physiology or Medicine 2021
    How do you feel? The molecules that sense touch [Nobel Lecture video | Read the Lecture | Source]

  • Edvard I. Moser, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
    Nobel Prize in Physiology or Medicine 2014
    Grid Cells and the Enthorinal Map of Space [Nobel Lecture video | Lecture Slides | Read the Lecture | Source]

  • May-Britt Moser, Norwegian University of Science and Technology (NTNU), Trondheim, Norway Nobel Prize in Physiology or Medicine 2014
    Grid Cells, Place Cells and Memory [Nobel Lecture video | Lecture Slides | Read the Lecture | Source]

  • John O’Keefe, University College, London, United Kingdom
    Nobel Prize in Physiology or Medicine 2014
    Spatial Cells in the Hippocampal Formation [Nobel Lecture video | Lecture Slides | Read the Lecture | Source]

  • Thomas C. Südhof, Stanford University
    The Nobel Prize in Physiology or Medicine 2013
    The Molecular Machine of Neurotransmitter Release [Nobel Lecture video | Lecture Slides | Read the Lecture | Source]

  • Linda B. Buck, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
    Nobel Prize in Physiology or Medicine 2004
    Unraveling the Sense of Smell [Nobel Lecture video | Lecture Slides | Read the Lecture | Source]

  • Richard Axel, Columbia University, New York, NY, USA
    Nobel Prize in Physiology or Medicine 2004
    Scents and Sensibility: A Molecular Logic of Olfactory Perception [Nobel Lecture video | Lecture Slides | Read the Lecture | Source]

  • Eric Kandel (1929-), Columbia University, New York, NY, USA
    Nobel Prize in Physiology or Medicine 2000
    The Molecular Biology of Memory Storage: A Dialog between Genes and Synapses [Nobel Lecture video | Read the Lecture | Source]

  • Paul Greengard (1925-2019), Rockefeller University, New York, NY, USA
    The Nobel Prize in Physiology or Medicine 2000
    The Neurobiology of Dopamine Signaling [[Nobel Lecture video | Read the Lecture | Source]

  • Arvid Carlsson (1923-2018), Göteborg University, Gothenburg, Sweden
    Nobel Prize in Physiology or Medicine 2000
    A Half-Century of Neurotransmitter Research: Impact on Neurology and Psychiatry [[Nobel Lecture video | Read the Lecture | Source]

  • Erwin Neher, Max-Planck-Institut für Biophysikalische Chemie, Göttingen, Germany
    Nobel Prize in Physiology or Medicine 1991
    Ion Channels for Communication Between and Within Cells [Nobel Lecture video | Read the Lecture | Source]

  • Bert Sakmann, Max-Planck-Institut für medizinische Forschung, Heidelberg, Germany
    Nobel Prize in Physiology or Medicine 1991
    Elementary Steps in Synaptic Transmission Revealed by Currents through Single Ion Channels [Nobel Lecture video | Read the Lecture | Source]

  • David H. Hubel, Harvard Medical School, Boston, MA, USA
    Nobel Prize in Physiology or Medicine 1981
    Evolution of Ideas on the Primary Visual Cortex, 1955-1978: A Biased Historical Account [Nobel Lecture video | Read the Lecture | Source]

  • Torsten N. Wiesel, Harvard Medical School, Boston, MA, USA
    Nobel Prize in Physiology or Medicine 1981
    The Postnatal Development of the Visual Cortex and the Influence of Environment [Nobel Lecture video | Read the Lecture | Source]

  • Julius Axelrod, National Institutes of Health, Bethesda, MD, USA
    Nobel Prize in Physiology or Medicine 1970
    Noradrenaline: Fate and Control of Its Biosynthesis [Read the Lecture | Source]

  • Ulf von Euler, Karolinska Institutet, Stockholm, Sweden
    Nobel Prize in Physiology or Medicine 1970
    Adrenergic Neurotransmitter Functions [Read the Lecture | Source]

  • Sir Bernard Katz, University College, London, United Kingdom
    Nobel Prize in Physiology or Medicine 1970
    On the Quantal Mechanism of Neural Transmitter Release [Read the Lecture | Source]

  • Alan Lloyd Hodgkin, University of Cambridge, Cambridge, United Kingdom
    Nobel Prize in Physiology or Medicine 1963
    The Ionic Basis of Nervous Conduction [Read the Lecture | Source]

  • Andrew Fielding Huxley, University College, London, United Kingdom Nobel Prize in Physiology or Medicine 1963
    The Quantitative Analysis of Excitation and Conduction in Nerve [Read the Lecture | Source]

  • Santiago Ramón y Cajal, Madrid University, Madrid, Spain
    Nobel Prize in Physiology or Medicine 1906
    The Structure and Connexions of Neurons [Read the Lecture | Source]

  • Camillo Golgi, Pavia University, Pavia, Italy
    Nobel Prize in Physiology or Medicine 1906
    The Neuron Doctrine – Theory and Facts [Read the Lecture | Source]