Synapses Podcast

Overview of Synapses

• First Description: Sir Charles Sherrington described the synapse in the late 19th century, inferring its existence by observed behavioral delays in reflexes.

Historical Experiments

• Otto Levy's Experiment:

  • Demonstrated the existence of vagus substance (Vegesstauf) through an experiment with frog hearts.

  • Used two frog hearts, one innervated by the vagus nerve and one denervated.

  • Dripped ringer solution over the innervated heart to see if it affected the other heart.

  • The vagus nerve causes parasympathetic input that slows heart rate.

  • After stimulating the vagus nerve, both hearts synchronized, confirming evidence of vagus substance now known as acetylcholine.

Development of Synapse Theories

• Physiological Camps:

  • Emerged a debate between electrical synapse proponents ("sparks") and chemical synapse advocates ("goober physiologists").

  • By 1954, both types of synapses were determined to exist, with chemical synapses being more prevalent.

Structure of Synapses

• Types of Synapses:

  • Electrical Synapse:

    • Characterized by aligned presynaptic and postsynaptic membranes, allowing ion flow directly.

    • Only excitatory synapses possible; no inhibitory synapses due to ion flow configuration.

  • Chemical Synapse:

    • Defined by a synaptic gap filled with fluid between presynaptic and postsynaptic membranes.

    • Introduces additional jargon: "synaptic gap" and "synaptic cleft."

    • Involves synaptic boutons, vesicles, and densities that are pivotal in neurotransmitter release.

Chemical Transmission Evidence

• Evidence for Chemical Synapses:

  1. Recordable excitatory and inhibitory postsynaptic potentials.

  2. No postsynaptic change during presynaptic potentials.

  3. Delay between pre and postsynaptic potentials (~0.3 ms).

  4. Larger-than-expected postsynaptic potentials from electrical induction.

Criteria for Neurotransmitters

• Five Standardized Requirements for chemical substances to qualify as neurotransmitters:

  1. Substance or its precursor must be present in presynaptic terminals.

  2. Action potentials must trigger release of the substance.

  3. Physiological concentrations of the substance must activate the postsynaptic membrane.

  4. An inactivating enzyme must be present near the synapse.

  5. Specific drugs must be able to block transmission predictably.

Action Potentials vs. Graded Potentials

• Comparison:

  • Action Potentials:

    • Are all-or-nothing, self-propagated, and nondecremental.

    • Have a defined threshold.

  • Graded Potentials:

    • Can vary in magnitude, are non-propagated, and decremental.

    • Do not have a threshold.

Summation Processes

• Post-Synaptic Summation:

  • Spatial Summation:

    • Multiple presynaptic neurons must stimulate the postsynaptic cell simultaneously for action potential generation.

  • Temporal Summation:

    • A single neuron must fire multiple times in a short period for action potential generation.

Synaptic Transmission Process

• Transmission Dynamics:

  • Action potential depolarizes bouton, opens calcium channels, allowing calcium influx which triggers vesicle migration and neurotransmitter release into the synapse.

• Deactivation Mechanisms:

  • Involvement of extracellular enzymes, reuptake through pinocytosis, and autoreceptors that self-regulate transmitter release.

Postsynaptic Receptor Types

• Two Basic Categories:

  1. Ionotropic Receptors:

     • Direct action; transmitter binding leads to immediate ion flow affecting excitatory or inhibitory outcomes.

  2. Metabotropic Receptors:

     • More complex; initiate biochemical processes involving G proteins and secondary messengers leading to longer-lasting effects.

Dale's Principle and Its Limitations

• Dale's Principle: Original notion that a neuron releases only one type of neurotransmitter.

• Corollary: Same transmitter released at all synapses of a single neuron.

• Modern Findings:

  • Evidence reveals that co-release of multiple transmitters from a single bouton is possible and that different transmitters can be released at different synapses of the same neuron.

Synaptic Configurations

• Different Synaptic Types:

  • Includes axodendritic, axosomatic, axoaxonic, somatosomatic, dendrodendritic, and more.

• Axoaxonic Synapses:

  • In these, one neuron's bouton synapses onto another neuron's bouton.

  • Can facilitate or inhibit neurotransmitter release, akin to presynaptic inhibition or facilitation.