Chemical Events at the Synapse

Learning Objectives

  • List and explain the sequence of events at a synapse from neurotransmitter synthesis to their disposition.
  • Distinguish between ionotropic and metabotropic receptors and their functions.
  • Discuss the impact of certain drugs on behavior due to their effects at synapses.
  • List some hormones and their effects.

Introduction to Synaptic Transmission

  • Charles Sherrington proposed that synaptic transmission was electrical, influenced by the speed of synaptic activity compared to axon transmission.
  • Although Sherrington was partly correct, most synapses rely on chemical processes, which are fundamental for communication in the nervous system.

Historical Perspective on Chemical Transmission

  • Key Figures:
    • T.R. Elliott (1905): Suggested that sympathetic nerves release adrenaline, influencing various organs (e.g., heart rate, pupil dilation).
    • Otto Loewi (1920): Demonstrated chemical transmission definitively through experiments with frog hearts, showing that neurotransmitters were involved.
    • Loewi stimulated the vagus nerve of one heart, extracted the surrounding fluid, and transferred it to another heart, demonstrating chemical mediation in heart rate changes.
Key Experiments and Findings
  • Loewi’s Experiment:
    • Procedure:
    1. Stimulated vagus nerve - decreases heart rate.
    2. Collected fluid - transferred to another frog heart, observed a similar decrease in heart rate.
    3. Stimulated accelerator nerve - observed increased heart rate in the second frog heart.
  • Importance: This experiment laid groundwork for understanding synaptic chemical transmission, leading to Loewi's Nobel Prize.

Sequence of Chemical Events at the Synapse

  1. Synthesis of Neurotransmitters:
    • Occurs in the neuron cell body or axon terminal.
  2. Action Potential Arrival:
    • Action potentials reach presynaptic terminal, causing calcium influx.
  3. Neurotransmitter Release:
    • Calcium triggers exocytosis, releasing neurotransmitters into the synaptic cleft.
  4. Receptor Binding:
    • Neurotransmitters diffuse and bind to receptors on the postsynaptic neuron.
  5. Receptor Activation:
    • Alters the activity of the postsynaptic neuron via ionotropic or metabotropic mechanisms.
  6. Termination of Signal:
    • Neurotransmitters detach from receptors and are either recycled or diffused away.
  7. Negative Feedback Mechanisms:
    • Some neurons send signals back to regulate neurotransmitter release.

Types of Receptors

Ionotropic Receptors
  • Fast-acting receptors that allow ions to flow directly into the cell when activated.
  • Example:
    • Glutamate Receptors: Primarily excitatory, allowing Na⁺ inflow.
    • GABA Receptors: Primarily inhibitory, allowing Cl⁻ inflow.
  • Effects are swift, often within milliseconds.
Metabotropic Receptors
  • Engage cellular signaling pathways and produce slower, longer-lasting effects via second messengers.
  • Example:
    • G protein-coupled receptors that can influence gene expression, ion channel activity, and more.
  • Effects can last from seconds to minutes or longer.

Neurotransmitters

Types and Functions
  • Amino Acids:
    • Glutamate, GABA, glycine, aspartate.
  • Modified Amino Acids:
    • Acetylcholine.
  • Monoamines:
    • Serotonin, dopamine, norepinephrine, epinephrine.
  • Neuropeptides:
    • Endorphins, substance P.
  • Gases:
    • Nitric oxide (NO).
  • There's a high conservation of neurotransmitter types across many species.

Synthesis of Neurotransmitters

  • Most neurotransmitters synthesized from dietary amino acids.
  • Example:
    • Acetylcholine: Synthesized from choline; significant dietary sources include milk, eggs, peanuts.
    • Dopamine and Norepinephrine: Derived from phenylalanine and tyrosine.

Drugs and Synaptic Effects

  • Drugs significantly alter synaptic processes affecting behavior:
    • Stimulants (e.g., cocaine, amphetamines): Block reuptake of neurotransmitters leading to prolonged effects.
    • Antidepressants: Inhibit reuptake to increase neurotransmitter availability.
    • Hallucinogens (e.g., LSD): Resemble serotonin and stimulate specific receptors leading to altered perception.
    • Opiates: Attaching to endorphin receptors provide pain relief and euphoria.
  • Negative feedback mechanisms via autoreceptors help regulate neurotransmitter release.

Hormones and Their Effects

  • Hormones serve longer-term regulation compared to the rapid neurotransmitter signaling.
  • Secreted by glands, transported via blood, influencing target organs:
    • Important Hormones:
    • Oxytocin (posterior pituitary), Growth Hormone (anterior pituitary), Cortisol (adrenal cortex).
  • Hormonal influences can have similar effects as synaptic transmission, but with longer durations.

Summary of Key Concepts

  • Synapses communicate through chemical neurotransmission.
  • The majority of neurotransmitter effects are rapid yet can vary widely based on the receptor type and pathways activated.
  • Understanding neurotransmitter dynamics lays the foundation for comprehending brain function and behavior influences, whether through natural signaling or pharmacological manipulation.