What Are the Ten Most Elegant and Decisive Neuroscience Experiments?

Can you help me identify the ten most elegant and or decisive experiments in the history of neuroscience?

I think that HH’s voltage clamp I/V measurements make it in.  Perhaps the freeze fracture experiments demonstrating vesicular release.

10 Comments

  1. gualtiero

    I’m no expert but the ones you suggest sound right. A couple of other things that come to mind are:

    Galvani showing that nerve cells produce electricity.

    The experiments that demonstrated the “all-or-none” law of nervous activity.

    Lettvin, Maturana, McCulloch and Pitts discovering “bug detectors” in the frog’s visual system.

  2. Ken

    Loewi’s experiments on chemical transmission and the vagus seem pretty decisive, but I’m not so sure that they were elegant.

    (Interestingly, McCulloch (G’s friend and mine) seems to have resisted chemical transmission even as late as his “Logical Calculus” paper with Pitts (1943).)

    And I’m blocking on the details, but what convinced Eccles that there exists inhibitory synapses?

    And there has to be something about Ramon y Cajal and the existence of synapses.

    So, something in those three general areas seem to me to be reasonable nominees. I’m not sure how to pin it down to specific papers …

  3. Ken

    Loewi’s experiments on chemical transmission and the vagus seem pretty decisive, but I’m not so sure that they were elegant.

    (Interestingly, McCulloch (G’s friend and mine) seems to have resisted chemical transmission even as late as his “Logical Calculus” paper with Pitts (1943).)

    And I’m blocking on the details, but what convinced Eccles that there exists inhibitory synapses?

    And there has to be something about Ramon y Cajal and the existence of synapses.

    So, something in those three general areas seem to me to be reasonable nominees. I’m not sure how to pin it down to specific papers …

  4. I suggest the experiment reported by Murray, Boyaci, and Kersten (2006) in *Nature Neuroscience* 9, 429-434. “The representation of perceived angular size in human primary cortex”.

    Using fMRI, they decisively demonstrate that the retinotopic brain representation of an object changes in accordance with a change in its perceived size even though its retinal size (visual angle) remains constant. “A distant object that appears to occupy a larger portion of the visual field activates a larger area in V1 than an object of equal angular size that is perceived to be closer and smaller”.

  5. Eric Thomson

    In no particular order (except number 1, which should be at that spot), and included for importance not elegance…I’m sure I’ll modify the list at some point in the future…
    1. Hodgkin Huxely’s 1952 papers.
    2. Katz’s papers on neurotransmitter release at the frog neuromuscular
    junction, and the mathematical model of said release (Vpost=npq).
    3. Golgi and Cajal’s contributions to anatomy, and especially their useful argument about the neuron doctrine versus the syncytium doctrine of neural organization.
    4. Hubel and Wiesel’s work on receptive fields in the visual sytem.
    5. Mu Ming Poo and Henry Markram’s demonstration of spike-timing dependent plasticity.
    6. Sperry’s work on split-brain patients.
    7. Aserinsky’s discovery of sleep cycles via the EEG. Opened up tons of research.
    8. HM (anterograde amnesia after bilateral hippocampal lesion), described initially by I’m not sure whom.
    9. Channelrhodopsin (development of light-activated ion channels). I don’t remember who did it, but there’s a ton on the web about it now.
    10. Rall’s analysis of dendritic cables.

    Honorable mention:
    a. Blindsight
    b. Broca and Wernicke’s work on linguistic disorders.
    c. Development of dynamic clamp (controls conductance rather than current or voltage, so mimics what actually changes when ion channels open and close).
    d. Galvani
    e. Goldman-Hodgkin-Katz derivation of the equation to determine the
    voltage across a membrane when there are different ion species (in
    different concentrations) inside and outside a membrane.
    f. What the frog’s eye tells the frog’s brain.
    g. Sherrington integrative action, where he introduces the idea of the synapse.
    h. First paper demonstrating functional MRI (Ogawa et al 1990).

  6. -The Bell-Magendie Law
    (Sir Charles Bell and Francois Magendie)
    for their
    discovery of the sensory and motor conduction of the spinal nerves roots (ventral roots for motor and dorsal for sensory signals)
    -More modern ones, Sperry´s chemoaffinity hypothesis (all cells are matched chemically for meeting), Rita levi Montalcini for their discovery of the nerve growth factor (NGF)critical for organogenesis and Paul Ehrlich for his discovery of the blood-brain-barrier critical for drug delivery in hte brain and therapy.

  7. David Michael Kaplan

    Great question, Carl. And many great suggestions above. Here’s a few more that might be worth considering (roughly in chronological order):

    1. Brodmann’s cytoarchitectural studies and subsequent classification scheme for cortex.
    2. Hartline’s studies of the retinal action potential (1940s)
    3. Mountcastle’s studies of columnar functional organization in somatosensory cortex (reported in his 1957 paper)
    4. Hubel & Wiesel’s work on critical developmental periods in visual system (reported in their 1963-1965 papers)
    5. von Békésy’s work on the function of the cochlea
    6. Evarts’ work on neuronal responses in alert, behaving animals (reported in his 1968 paper)

  8. Cory Wright

    all good suggestions, and one more to add to the pile: the Olds & Milner 1954 paper on medial forebrain bundle activity (which kicked off half a century of experiments on reward).

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