Synaptic Transmission

Overview

• The human brain consists of 86 billion neurons.
• Communication among these neurons is facilitated by synapses.

Types of Synapses

Two main types: Electrical and Chemical Synapses.

1. Electrical synapses use connexons for direct current flow.
   • Direct, passive flow of electrical current.
2. Chemical synapses use neurotransmitters for cell-to-cell communication.
   • Chemical: Communication via neurotransmitter release.

Feature	Electrical Synapses	Chemical Synapses
Structure	Gap junctions Connexons enable close neuron-to-neuron links	Larger synaptic cleft between neurons Synaptic vesicles in presynaptic terminal
Function	Direct flow of electrical current Current sourced from local potential difference	Neurotransmitters facilitate communication as chemical messengers
Key Characteristics	Permits passive electrical current flow Influenced by presynaptic action potential	Presence of neurotransmitters in synaptic vesicles Acts through specialized receptors on postsynaptic cell

• Electrical and chemical synapses differ fundamentally in their transmission mechanisms
• 

  (A) At electrical synapses, gap junctions occur between pre- and postsynaptic membranes. (B) Gap junctions contain connexon channels that permit current to flow passively from the presynaptic cell to the postsynaptic cell.

• 

  (C) At chemical synapses, there is no intercellular continuity, and thus no direct flow of current from pre- to postsynaptic cell. (D) Synaptic current flows across the postsynaptic membrane only in response to the secretion of neurotransmitters, which open or close postsynaptic ion channels after binding to receptor molecules on the postsynaptic membrane.

Overview of Chemical Synapses

• Presynaptic terminal with synaptic vesicles.
• Postsynaptic cell, separated by synaptic cleft.
• Filamentous elements in pre- and postsynaptic processes.
• Structures in synaptic cleft, including active zone and postsynaptic density.

Chemical Synapses and Neurotransmitters

• Over 100 different neurotransmitters identified.
• Communication process: Synthesis, packaging, release, and binding of neurotransmitters, followed by rapid removal or degradation.

Signaling Transmission Sequence at Chemical Synapses

1. 

   Sequence of events involved in transmission at a typical chemical synapse

   Synaptic Vesicle Preparation → ormation and filling of synaptic vesicles with neurotransmitter.
2. Action Potential Arrival - Invades presynaptic terminal → Opens voltage-gated Ca2+ channels.
3. Ca2+ Influx:
   • Rapid influx due to concentration gradient (10–3 M external vs. 10–7 M internal).
   • Elevates Ca2+ in presynaptic terminal.

Exocytosis and Postsynaptic Response

1. Exocytosis
   • Ca2+ elevation → Synaptic vesicles fuse with presynaptic membrane.
   • Neurotransmitters released into synaptic cleft.
2. Neurotransmitter Binding
   • Diffuses across cleft → Binds to postsynaptic receptors.
   • Opens/closes channels in postsynaptic membrane, altering ion flow.
3. Postsynaptic Neuron Response
   • Alters conductance and membrane potential.
   • Increases/decreases probability of firing an action potential.

Termination of Signal

• Neurotransmitter Removal
  • Uptake into glial cells or enzymatic degradation.
• Effect
  • Terminates neurotransmitter action.
  • Ensures transient information transmission from one neuron to another.

Slide 14: Overview of Chemical Synapse Transmission

• Neurotransmitter Role: Chemical signals like acetylcholine play critical roles in transmitting information across neurons, as demonstrated by Otto Loewi in 1926.
• Classification: Over 100 neurotransmitters identified, broadly categorized into small-molecule neurotransmitters and neuropeptides.

Slide 15: Neurotransmitter Diversity and Regulation

• Diverse Functions: Neurotransmitters can excite or inhibit postsynaptic neurons, with small-molecule neurotransmitters facilitating rapid responses and neuropeptides modulating slower functions.
• Co-Transmitters: Enable dynamic changes in signaling properties based on synaptic activity.
• Synaptic Regulation: Synthesis, packaging, release, and removal/degradation of neurotransmitters are tightly controlled to maintain appropriate levels.

Slide 16: Synaptic Vesicle Preparation and Action Potential

• Vesicle Formation: Synaptic vesicles are prepared by being filled with neurotransmitters, ready for release upon an action potential arrival.
• Action Potential's Role: Triggers the opening of voltage-gated Ca2+ channels in the presynaptic terminal, leading to Ca2+ influx due to the concentration gradient.

Slide 17: Exocytosis and Neurotransmitter Release

• Ca2+ Influx: Causes a rapid increase in presynaptic Ca2+ levels, facilitating the fusion of synaptic vesicles with the presynaptic membrane.
• Exocytosis: Releases neurotransmitters into the synaptic cleft, where they diffuse across to bind to postsynaptic receptors.

Slide 18: Postsynaptic Response and Signal Termination

• Neurotransmitter Binding: Alters postsynaptic ion flow by opening or closing channels, changing membrane potential and conductance.
• Neuron Firing Probability: Influences the likelihood of the postsynaptic neuron firing an action potential.
• Termination of Signal: Achieved through neurotransmitter uptake into glial cells or enzymatic degradation, ensuring the transient nature of the signal.

Synaptic Transmission at the Neuromuscular Junction (NMJ)

Neuromuscular Transmission and Nicotinic Synapses

• NMJ: Connection between alpha-motor neuron axons and skeletal muscle fibers.
• Mechanism: Cholinergic transmission using acetylcholine (Ach).
• Relevance: Basics of neurotransmitter release applicable across all synapses.

Sequence of Events in Synaptic Transmission

1. Action Potential Arrival: Depolarizes presynaptic membrane → opens voltage-gated Ca2+ channels.
2. Ca2+ Influx: Triggers release of Ach.
3. Ach Release and Binding: Binds to nicotinic receptor on muscle membrane → depolarization (EPP).
4. Muscle Action Potential: Triggered by EPP → muscle contraction.
5. Ach Breakdown: Acetylcholinesterase (AchE) terminates Ach action → reuptake of choline.

Other Cholinergic Synapses

• Neuronal Nicotinic (NN) Receptors: In autonomic ganglia, activated by presynaptic cholinergic neurons.
• Muscarinic Receptors: In parasympathetic target tissues, G-protein coupled receptors.

Synapses Between Neurons

• Location: On the cell body and dendrites.
• Influence: Closer synapses to the axon hillock have greater influence on action potential initiation.
• EPSP vs. IPSP: EPSP increases excitability (more likely to fire), while IPSP decreases excitability (less likely to fire).
• Key Receptors: EPSP (Nicotinic, Non-NMDA, NMDA), IPSP (GABAA&C, Glycine).

EPSP and IPSP Explained

• EPSP: Increased Na+ conductance, similar to EPP at NMJ.
• IPSP: Increased Cl- conductance, reducing neuron's excitability.
• Important Receptors:
  • EPSP: Nicotinic, Non-NMDA, NMDA (ligands: Ach, glutamate, aspartate).
  • IPSP: GABAA&C, Glycine (ligands: GABA, glycine).