Neurons and Synapses

Introduction to Synapses

• A synapse is a specialized site where a neuron communicates with another cell
• Synapses can occur between two neurons, a neuron and an effector cell, or a sensory cell and a neuron
• Presynaptic neurons impact the function of postsynaptic cells
• Action potentials in the presynaptic cell trigger the release of a synaptic transmission
• Synaptic transmission is the signal sent by the presynaptic cell to affect the postsynaptic cell
• Synaptic transmissions alter the membrane potential of the postsynaptic cell, either increasing or decreasing the likelihood of an action potential

Electrical Synapses

• Synapses are more commonly chemical, but some are electrical
• Chemical and electrical synapses serve different functional roles
• In an electrical synapse, the action potential spreads directly from one cell to another, making it extremely fast
• Cells using electrical synapses have specialized gap junctions
• Protein channels called connexons bridge the gap between cells, linking their cytoplasm
• Connexons bring the cells about 3.5 nm apart
• Electrical signals weaken slightly as they move from one cell to another
• Electrical synapses are used in escape circuits, such as the crawfish tail-flip

Chemical Synapses

• In chemical synapses, the action potential in the presynaptic cell is transduced into a chemical signal (neurotransmitter)
• Neurotransmitters are sent to the postsynaptic cell across the gap between the cells
• Synaptic vesicles in the presynaptic cell store thousands of neurotransmitter molecules
• Presynaptic cells have active zones where neurotransmitters are released
• The postsynaptic membrane possesses postsynaptic densities
• Receptor proteins for neurotransmitters are located in the postsynaptic densities
• Chemical synapses are separated from other cells by a 20 to 30 nm space called the synaptic cleft

Basic Steps of Chemical Synapses

• An action potential depolarizes the presynaptic terminal, opening voltage-gated Ca2+ channels
• Ca2+ moves into the cell because its concentration is lower inside than outside
• Ca2+ influx triggers neurotransmitter release into the synaptic cleft via calcium-dependent exocytosis
• Exocytosis is the fusion of synaptic vesicles to the presynaptic membrane
• Neurotransmitter molecules bind to specific receptor proteins embedded in the postsynaptic membrane
• Enzymes degrade neurotransmitters, or they are taken back into the presynaptic cell
• Neurotransmitter molecules travel across the synaptic cleft in 20-50 microseconds

Types of Chemical Synapses

• Synapse type is based on the receptor the neurotransmitter binds to
• Neurotransmitter receptor types are:
• Ionotropic receptors directly alter permeability to ions
• Ionotropic receptors produce rapid changes in membrane potential by allowing ions to flow into the cell and are ligand-gated ion channels
• Metabotropic receptors trigger a signaling cascade of second messengers in the postsynaptic cell and have slow but long-lasting effects
• Chemical synapses are slower than electrical synapses

Advantages of Chemical Synapses

• Chemical synapses can amplify the response in the postsynaptic cell
• Electrical synapses typically weaken from cell-to-cell
• Chemical synapses can be either excitatory or inhibitory
• Electrical synapses are nearly always excitatory
• Chemical synapses are more finely controlled and plastic than electrical synapses
• Presynaptic cells can release differing types or amounts of neurotransmitter and postsynaptic cells have different types and numbers of receptors

Classes of Neurotransmitters I

• Neurotransmitters are divided into two major classes
• Small-molecule neurotransmitters are usually single amino acids and their derivatives
• They are synthesized in axon terminals from metabolic precursors
• They are packaged into small synaptic vesicles by vesicular transporter molecules on the vesicle surface
• An example is dopamine, which is derived from tyrosine in the axon terminal
• They are released by calcium-dependent exocytosis

Classes of Neurotransmitters II

• Neuropeptides are chains of 3-55 amino acids
• They are synthesized on ribosomes in the neuronal cell body (soma) as propeptides, which contain several copies of neurotransmitter
• Large dense-cored vesicles transport the propeptides to the axon terminals
• Propeptides are cleaved inside these vesicles to make the active neurotransmitters
• The release of peptide neurotransmitters requires a higher frequency of presynaptic action potentials compared to small-molecule transmitters
• Exocytosis of these vesicles is not at active zones where Ca2+ enters, so greater Ca2+ influx is necessary
• Neuropeptides are always broken down after release

Neurotransmitter Functional Classes

• CNS neurotransmitters are divided into general functional classes based on their effect and location
• Most neurotransmitters in the CNS are small-molecule neurotransmitters
• Glutamate is mostly excitatory
• GABA and glycine are inhibitory
• Amines (acetylcholine, norepinephrine, dopamine, serotonin) are in fewer cells of the CNS, but are widespread
• They typically produce a slow response in postsynaptic cells
• Peptides are common in the CNS and are often released along with small-molecule neurotransmitters

Cotransmitters and the Evolution of Neurotransmitters

• Neurons can contain and release more than one kind of neurotransmitter
• Cotransmitters are neurotransmitters released by a single neuron
• Neurons often contain and release a small-molecule neurotransmitter and one or more neuropeptides
• Transmitters can be released from the same vesicle if they are the same type of neurotransmitter, such as dopamine and GABA
• Most neurotransmitters are conserved across animal taxa

Neurotransmitter Release

• Vesicles containing neurotransmitters are prepared by the cell
• After an influx of Ca2+ ions, vesicles dock with the axon membrane
• Vesicles will then either:
• Fuse fully with the membrane (classical exocytosis) and release neurotransmitter, or fuse only partially with the membrane (kiss-and-run fusion) and release neurotransmitter
• Retrieval of the vesicle
• In classical exocytosis, the vesicle is endocytosed with the aid of clathrin and dynamin
• In kiss-and-run fusion, the vesicle is not fully fused and does not need to undergo the full process of endocytosis

Synaptic Potentials

• Postsynaptic potential (PSP) is generated in the postsynaptic cell after it binds neurotransmitters from a presynaptic cell

• PSP is a short change in the resting membrane potential of the postsynaptic cell

• Excitation is an increase in the probability that a cell will generate an action potential

• It creates excitatory postsynaptic potentials (EPSPs)

• Inhibition is a decrease in the probability that a cell will generate an action potential

• It creates inhibitory postsynaptic potentials (IPSPs)

• Changes in membrane potential in postsynaptic cells are controlled by changes in the permeability of the cell’s membrane to ions

• When acetylcholine binds its receptor, the receptor (which is also an ion channel) opens and allows Na+ and K+ to enter/leave the cell more easily

• Most neurotransmitters affect more than one kind of neurotransmitter receptor

• The effects of a neurotransmitter depend on the type of receptors in the postsynaptic cell membrane

• Acetylcholine excites skeletal muscle cells but inhibits heart muscle cells because these muscle cells have different receptors for acetylcholine

• Nicotinic receptors are in skeletal muscle

• Muscarinic receptors are in heart muscle