Synapses and Neurotransmitters

Overview of Synapses and Signal Transmission

  • Definition of Synapses: Synapses are the functional junctions that allow for the transmission of signals between neurons or between a neuron and an effector cell.

  • Primary Types of Synapses:

    • Electrical Synapses: These synapses facilitate the passage of electrical signals directly from one cell to another through gap junctions.

    • Chemical Synapses: These function by releasing chemical messengers known as neurotransmitters. These chemicals must cross a physical gap called the synaptic cleft to reach the target cell.

Anatomy and Structure of a Chemical Synapse

  • Presynaptic Neuron: This is typically the axon of the neuron sending the signal.

    • Axon Terminals: The distal terminations of the axon.

    • Synaptic Vesicles: Specialized membrane-bound sacs located within the axon terminal that contain neurotransmitters.

  • Synaptic Cleft: An extremely small fluid-filled space located between the presynaptic and postsynaptic membranes.

  • Postsynaptic Cell/Neuron: The receiving cell which contains specific protein receptors for neurotransmitters.

  • Anatomical Variations of Synapses:

    • Axodendritic Synapses: Connection between the axon of one neuron and the dendrites of another.

    • Axosomatic Synapses: Connection between the axon of one neuron and the cell body (soma) of another.

    • Axoaxonal Synapses: Connection between the axon of one neuron and the axon of another.

The Process of Signal Transfer Across a Synapse

  1. Activation: An incoming action potential reach the axon terminal and activates voltage-gated Ca+Ca^{+} channels.

  2. Calcium Influx: The opening of these channels allows an influx of Ca+Ca^{+} into the presynaptic terminal.

  3. Vesicle Fusion: The increase in intracellular calcium causes synaptic vesicles to move toward and fuse with the presynaptic membrane.

  4. Exocytosis: The neurotransmitters contained within the vesicles are released into the synaptic cleft via exocytosis.

  5. Diffusion: Neurotransmitters diffuse across the synaptic cleft.

  6. Receptor Binding: Neurotransmitters bind to specific protein receptors located on the postsynaptic membrane.

  7. Ion Channel Response: Binding to chemically-gated (ligand-gated) ion channels triggers an influx of specific ions into the postsynaptic cell.

Postsynaptic Potentials and Signal Dynamics

  • Types of Postsynaptic Potentials:

    • Excitatory Postsynaptic Potential (EPSP):

      • Caused by Na+Na^{+} influx.

      • The inside of the cell becomes more positive.

      • Result: Depolarization of the membrane.

    • Inhibitory Postsynaptic Potential (IPSP):

      • Caused by Cl−Cl^{-} influx or K+K^{+} efflux.

      • The inside of the cell becomes more negative.

      • Result: Hyperpolarization of the membrane.

  • Factors Determining Signal Strength: The strength of the postsynaptic signal is directly proportional to:

    • The total amount of neurotransmitter released by the presynaptic neuron.

    • The duration of time the neurotransmitter remains active in the synaptic cleft.

  • Termination of the Signal: Synaptic signaling is ended through several mechanisms:

    • Cessation of further neurotransmitter release.

    • Reuptake: The neurotransmitter is absorbed back into surrounding cells or the presynaptic terminal.

    • Degradation: Enzymes within the cleft break down the neurotransmitter.

    • Diffusion: The neurotransmitter simply diffuses out of the synapsis.

Integration of Synaptic Events and Summation

  • Summation of EPSPs: Individual EPSPs are often too weak to trigger an action potential; they must combine through summation.

    • Temporal Summation: Occurs when two or more stimuli are delivered to the postsynaptic neuron in rapid succession (close in time). If the time interval is too great, the signals do not summate.

    • Spatial Summation: Occurs when the postsynaptic neuron is stimulated by a large number of different terminals simultaneously (close physically). Spatial summation can also lead to the canceling out of signals if excitatory and inhibitory inputs occur at the same time.

  • Synaptic Potentiation: The repeated or continuous use of a synapse enhances the presynaptic neuron's ability to excite the postsynaptic neuron. This is driven by an increase in Ca+Ca^{+} concentration within the presynaptic terminal.

  • Inhibition Mechanisms:

    • Presynaptic Inhibition: The release of an excitatory neurotransmitter by one neuron is inhibited by an inhibitory neurotransmitter released by a different neuron. This directly inhibits the release of neurotransmitters.

    • Post-synaptic Inhibition: The release of an inhibitory neurotransmitter directly negates the effect of an excitatory neurotransmitter on the postsynaptic cell. This directly inhibits the development of an action potential.

Classification and Characteristics of Neurotransmitters

  • General Overview:

    • More than 5050 different neurotransmitters have been identified to date.

    • A single neuron can release different types of neurotransmitters depending on the frequency of stimulation.

  • Chemical Groups:

    • Acetylcholine (ACh):

      • Found at neuromuscular junctions and within the Central Nervous System (CNS).

      • Release is inhibited by botulism toxin.

      • Muscle cell receptors are inhibited by curare.

      • Receptors are destroyed in the autoimmune condition Myasthenia Gravis.

      • Degraded by the enzyme acetylcholinesterase.

      • Acetylcholinesterase inhibitors (which keep ACh active longer) include nerve gas and insecticides such as malathion.

    • Biogenic Amines:

      • Catecholamines:

        • Norepinephrine: Prepares the body for action. Release is enhanced by amphetamines; degradation is blocked by cocaine and certain antidepressants.

        • Dopamine: Associated with "feel good" reward-motivated behavior. Deficiencies lead to Parkinson’s disease, while excessive levels are linked to schizophrenia.

    • Amino Acids:

      • GABA (\gamma-aminobutyric acid): The principal inhibitory neurotransmitter of the brain.

      • Glycine: The principal inhibitory neurotransmitter of the spinal cord.

      • Glutamate: The principal excitatory neurotransmitter of the entire nervous system.

    • Peptides:

      • Endorphins: Function as natural opiates to inhibit the perception of pain.

Neurotransmitter Receptors and Postsynaptic Responses

  • Ionotropic Receptors: These are ligand-gated ion channels. They provide a rapid, short-acting response by creating fast synaptic potentials.

  • Metabotropic Receptors: These are G-protein coupled receptors (GPCRs). They provide a slower response and are often referred to as neuromodulators. They create slow synaptic potentials and long-term effects by:

    • Activating second messenger pathways (e.g., using G-proteins and intracellular signals).

    • Altering the open/closed state of ion channels.

    • Modifying existing proteins or regulating the synthesis of new proteins.

    • Examples of outcomes: Na+Na^{+} in/K+K^{+} out (EPSP), or Cl−Cl^{-} in/K+K^{+} retention (IPSP).

Specific Functional Examples of Synapses

  • Cholinergic Synapse:

    • Uses Acetylcholine as the neurotransmitter.

    • Utilizes chemically-gated ion channel receptors.

    • Results in a net influx of Na+Na^{+} into the postsynaptic cell, making it excitatory.

  • GABA-ergic Synapse:

    • Uses GABA as the neurotransmitter.

    • Utilizes chemically-gated ion channel receptors (specifically Cl−Cl^{-} channels).

    • Results in a net influx of Cl−Cl^{-} into the postsynaptic cell, causing hyperpolarization. This makes the synapse inhibitory.

  • Adrenergic Synapse:

    • Uses Norepinephrine as the neurotransmitter.

    • Features G-protein coupled receptors.

    • Process: NE binds to receptor $\rightarrow$ activates G protein $\rightarrow$ activates Adenylate cyclase $\rightarrow$ converts ATP to cAMP (second messenger).

    • Effects: cAMP can open ligand-regulated Na+Na^{+} gates, activate enzymes, induce metabolic changes, or trigger genetic transcription/enzyme synthesis.

    • Characteristics: Delayed response and significant signal amplification.

Neuronal Pools and Functional Circuits

  • Diverging Circuit: One input triggers many outputs. This is an amplifying circuit. Example: A single brain neuron can activate 100100 or more motor neurons in the spinal cord, which in turn control thousands of skeletal muscle fibers.

  • Converging Circuit: Many inputs converge into one output. This is a concentrating circuit. Example: Different sensory stimuli (vision, smell, sound) can all converge to elicit the same single memory.

  • Reverberating Circuit: A signal travels through a chain of neurons, with some neurons providing feedback to previous ones in the chain. This is an oscillating circuit that controls rhythmic activity. Example: Breathing, the sleep-wake cycle, and repetitive motor actions like walking.

  • Parallel After-Discharge Circuit: An input signal stimulates neurons arranged in parallel arrays that eventually converge on a single output cell. Because the paths vary in length/synapses, impulses reach the output cell at different times, causing a burst of impulses called an after-discharge. Example: Potentially involved in complex mental processes like mathematical calculations.