Otto Loewi's 1921 frog heart experiment definitively proved that neurons communicate via chemical messengers, not just electrical signals. This outperforms #2 fMRI in direct molecular identification of signaling mechanisms, as it provided the first evidence of synaptic transmission. The discovery led to the identification of dopamine, serotonin, GABA, and others, with over 50% of psychiatric drugs today targeting these neurotransmitters. Its foundational role is reflected in more than 20,000 studies involving synaptic transmission, establishing a pillar of modern neuroscience.

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