Synaptic Transmission Chapter 5 Textbook
Synaptic Transmission
Introduction to Synaptic Transmission
Synaptic Transmission Definition: The process of information transfer from one neuron to another at specialized sites called synapses.
Origin of Term: Coined by English physiologist Charles Sherrington in 1899 (though the text says 1897).
Historical Debate: For almost a century, the physical nature of synaptic transmission was debated:
Electrical Transmission Hypothesis: Proposed that electrical current simply flowed from one neuron to the next, explaining the observed speed.
Proof: The existence of electrical synapses was finally proven in the late 1950s by Edwin Furshpan, David Potter (crayfish), and Akira Watanabe (lobster).
Prevalence: Electrical synapses are now known to be common in invertebrates and vertebrates, including mammals.
Chemical Transmission Hypothesis: Proposed that chemical neurotransmitters transfer information at the synapse.
Early Support (Otto Loewi, 1921): Provided solid evidence for chemical synapses through his frog heart experiment (Box 5.1).
Further Proof: Bernard Katz and colleagues conclusively demonstrated chemical mediation at the neuromuscular junction. John Eccles (using glass microelectrodes in 1951) showed many CNS synapses also use chemical transmitters.
Prevalence: Chemical synapses constitute the majority of synapses in the brain.
Complexity: Recent advances in molecular study have revealed synapses to be far more complex than previously anticipated.
Significance: Understanding synaptic transmission is crucial for comprehending:
The actions of psychoactive drugs.
The causes of mental disorders.
The neural bases of learning and memory.
All fundamental operations of the nervous system.
Chapter Focus: This chapter primarily focuses on the basic mechanisms of chemical synaptic transmission.
Box 5.1: Otto Loewi’s Dream
Key Discovery: Otto Loewi's experiment in the 1920s definitively showed that synaptic transmission between nerves and the heart is chemically mediated.
Experimental Setup:
The frog heart has two types of innervation: one speeds the heart, the other (vagus nerve) slows it.
Loewi isolated a frog heart with intact vagal innervation and electrically stimulated the vagus nerve, observing the expected slowing of the heartbeat.
Crucial Step: He then applied the solution that had bathed the first heart (containing released chemicals) to a second isolated frog heart.
Result: The second heart also slowed, demonstrating that a chemical substance released by the nerve mediated the effect.
Origin of the Idea: The idea for this experiment famously came to Loewi in a dream on Easter Sunday, 1921. After initially being unable to decipher his jotted notes, he re-dreamed the idea, immediately went to the laboratory, and confirmed it.
Scientific Boldness: Loewi noted that
Synaptic Transmission
Introduction to Synaptic Transmission
Synaptic Transmission Definition: The fundamental process of information transfer from one neuron to another, or from a neuron to an effector cell (like a muscle or gland), occurring at specialized junctions called synapses. This process is essential for all nervous system functions, from simple reflexes to complex cognitive processes.
Origin of Term: The term "synapse" was coined by the English physiologist Charles Sherrington in 1897. He deduced the existence of these specialized junctions based on his physiological experiments.
Historical Debate: For almost a century, from Sherrington's initial insights until the mid-\text{20}^{\text{th}} century, the precise physical nature of synaptic transmission was a subject of intense debate among neuroscientists:
Electrical Transmission Hypothesis: Proponents of this hypothesis believed that electrical current simply flowed directly from the presynaptic neuron to the postsynaptic neuron, explaining the remarkably rapid speed of neural communication.
Mechanism: In this model, ions would pass directly through channels connecting the cytoplasm of two cells.
Proof: The existence of electrical synapses was finally proven in the late 1950s by Edwin Furshpan and David Potter, working with crayfish, and Akira Watanabe, studying lobsters. They identified gap junctions (connexons) as the structures facilitating direct electrical current flow.
Prevalence and Function: Electrical synapses are now known to be common in both invertebrates and vertebrates, including mammals. They allow for very fast, synchronous activity among populations of neurons, important in escape reflexes and coordinating the activity of large groups of interneurons. Transmission is typically bidirectional.
Chemical Transmission Hypothesis: This opposing hypothesis proposed that information was transferred across a synaptic gap by means of chemical messengers, known as neurotransmitters.
Mechanism: This involves the presynaptic neuron (axon terminal site) releasing chemical substances into a space called the synaptic cleft, which then act on receptors on the postsynaptic neuron (dendrites of new neuron).
Early Support (Otto Loewi, 1921): Provided the first definitive experimental evidence for chemical synapses through his classic frog heart experiment (detailed in Box 5.1). He identified "vagusstoff" (later identified as acetylcholine) as the chemical mediator.
Further Proof: Later, Bernard Katz and colleagues conclusively demonstrated chemical mediation at the neuromuscular junction, detailing the process of neurotransmitter release via vesicles. John Eccles, initially an electrical synapse proponent, later used glass microelectrodes in 1951 to show that many central nervous system (CNS) synapses also utilize chemical transmitters, recognizing the slower, more complex nature of chemical transmission.
Prevalence: Chemical synapses constitute the vast majority of synapses in the brain, offering greater flexibility, modulation, and integration compared to electrical synapses. Transmission is typically unidirectional.
Complexity: Recent advances in molecular biology, neuropharmacology, and imaging technologies have revealed synapses to be far more intricate and dynamic structures than previously anticipated. This complexity arises from:
The vast diversity of neurotransmitters (excitatory, inhibitory, modulatory).
Numerous subtypes of postsynaptic receptors, each with different signaling properties.
Complex intracellular signaling cascades triggered by receptor activation.
Synaptic plasticity, the ability of synapses to change their strength over time, which underlies learning and memory.
The presence of neuromodulators that can fine-tune synaptic transmission.
Significance: Understanding the mechanisms of synaptic transmission is profoundly important for comprehending:
The actions of psychoactive drugs: Most psychiatric medications and recreational drugs exert their effects by altering specific aspects of chemical synaptic transmission (e.g., neurotransmitter synthesis, release, reuptake, or receptor binding).
The causes of mental disorders: Many neurological and psychiatric conditions (e.g., depression, schizophrenia, Parkinson's disease, epilepsy) are linked to dysfunctions in synaptic transmission.
The neural bases of learning and memory: Changes in synaptic strength and connectivity (synaptic plasticity) are widely regarded as the cellular mechanisms underlying how the brain stores and retrieves information.
All fundamental operations of the nervous system: From sensory perception and motor control to emotions and cognition, every aspect of nervous system activity relies on efficient and precise synaptic communication.
Chapter Focus: This chapter primarily focuses on the basic mechanisms of chemical synaptic transmission, given its central role in brain function and its vast implications for health and disease.
Box 5.1: Otto Loewi’s Dream
Key Discovery: Otto Loewi's seminal experiment, conducted in the 1920s, provided the first unequivocal evidence that synaptic transmission between nerve endings and effector organs (specifically the heart) is mediated by chemical substances rather than direct electrical signals. This disproved the prevailing electrical theory for peripheral synapses.
Experimental Setup:
Loewi's experiment utilized two isolated frog hearts, each perfused with a Ringer's solution. The first heart retained its intact vagal innervation, while the second heart was denervated.
The vagus nerve is part of the parasympathetic nervous system (rest/digest mechanism) and, when stimulated, causes a slowing of the heartbeat.
Loewi first electrically stimulated the vagus nerve of the first isolated frog heart. As expected, the stimulation caused the heartbeat to slow down significantly.
Crucial Step: He then carefully collected the Ringer's solution that had been bathing the first heart during and after vagal stimulation. This solution, now containing any released chemicals, was then transferred and applied to the second, denervated isolated frog heart.
Result: Remarkably, the second heart also slowed its beating, even though its own nerves were not stimulated. This demonstrated conclusively that a chemical substance, released by the stimulated vagus nerve into the perfusate, mediated the inhibition of the heart rate. This chemical was later identified as acetylcholine, which Loewi initially called "vagusstoff."
Origin of the Idea: The inspiration for this groundbreaking experiment famously came to Loewi in two vivid dreams on Easter Sunday, 1921. After the first dream, he jotted down notes but couldn't decipher them. The idea recurred in a second dream later the same night, prompting him to immediately go to his laboratory and perform the experiment, confirming his hypothesis. This anecdote highlights the role of intuition and subconscious processing in scientific discovery.
Scientific Boldness: Loewi noted that his experiment not only demonstrated chemical transmission but also opened up the field of neurochemistry, showing that nerves communicate via specific chemical signals that can be isolated and identified. His work paved the way for understanding the molecular basis of neurological functions and disorders. He also recognized that this finding implied a much greater level of complexity and pharmacological manipulability in the nervous system than previously imagined.