Functional Definition of a Synapse
A place of communication in neurons where activity in one affects activity in the other. An older definition that does not answer the nature of transmission.
Sign of a Synapse
Activity in excitatory neurons, such as sensory neurons, produce EPSPs in the receiving cell by opening Na+ channels. Activity in inhibitory neurons, such as interneurons, produce EPSPs by opening K+ channels.
Two Methods of Synapsing
- Electrical synapsing via direct current flow between neurons. Done by pores (gap junctions) allowing direct flow of cytoplasm between cells. Fast, synchronous, and bidirectional
- Chemical signaling via release of neurotransmitter vesicles which bond to receptors on the receiving cell. More flexible: used for amplification, modification, and plasticity.
Gap junction Signaling Function
There is no space between neurons, so an AP spike in the signaling cell has an instantaneous EPSP in the receiving cell. However, the EPSP is small due to high membrane resistance across the gap junction. Dampens the current 100:1. Signaling is bidirectional, so it can unite alike populations of neurons.
Temporal Summation in Gap Junctions
High resistance and capacitance results in a long tau, so the EPSPs is slower and more drawn out compared to the previous AP. Direct current only occurs at 10 Hz. This means gap junctions are poor at recording individual APs but they are good at synchronizing slow, rhythmic activity across neuron populations.
Gap Junction Structure
Composed of 2 connexons at each side which meet. Connexons are 1.5 nm transmembrane proteins which are composed of 6 subunits (connexins). Each connexin four membrane spanning regions with loops. These connexons line up and fuse on each side to create the gap junction. Low pH or high intracellular calcium causes them to close.
Chemical Synapse Structure
Common features of all chemical synapses: –Vesicles aggregating in presynaptic area (reserve pool)
–20-50 nm gap (cleft)
–presynaptic active zone
–post-synaptic membrane density
–Astrocytes up-taking released NT
Active Zone
The region where presynaptic vesicles are docked and primed and ready for release. Vesicles in the active zone are called the readily-releasable pool. In the active zone there is a thickening of the membrane known as the presynaptic density.
Mechanics of Chemical Synapsing
Release of neurotransmitter molecules at high concentration in well-defined space. This is done by calcium influx through VGCaCs binding to calcium sensors. Calcium influx is delayed to after the AP peaks due to driving force. Then the neurotransmitter molecules must be able to be recognized and have that recognition cause some sort of effect.
Presynaptic Density
Contains the readily releasable pool of vesicles docked and primed for release. Also contains scaffolding proteins where the vesicles dock
Postsynaptic Density
Neurotransmitter receptors clustered opposite of the presynaptic active zone, with some scaffolding proteins underneath: tethering receptors and effector cells to the actin cytoskeleton.
Presynaptic Grid
A series of triangular protrusions where synaptic vesicles bind and are held in a process called docking. Later they are chemically prepared for release in a process called priming. Forms precise spots opposite of postsynaptic receptors for vesicles to be docked.
Synapse Locations
Can occur at any part of the receiving neuron. Categorized as axodendritic, axosomatic, or axoaxonic.
Patch Clamp Recording
Electrode records the electrical activity on a synapse. Shows that distant EPSPs still make a large contribution due to long lambda. Different spines on the same dendrite show different activity, which is integrated at the initial segment.
Morphological Types of Synapse
Type I Synapses are excitatory with round glutamate vesicles, a wide cleft, and a thick postsynaptic density.
Type II Synapses are Inhibitory with flat GABA vesicles, a narrow cleft, and a thin postsynaptic density.
Presynaptic Inhibition
Activation of axoaxonic inhibitory neurons prevents the release of neurotransmitter whether through opening K+ channels draining current from the AP or through preventing Ca2+ channels from opening. Either way leads to not enough neurotransmitter being released to cause a spike in the receiving neuron. Occurs just before synaptic terminal.
Modulation
Inhibition without causing an IPSP, such as in presynaptic inhibition.
Temporal and Spatial Summation
Temporal: If two EPSPs are triggered within the tau value then the spike is triggered. Longer tau gives a more generous window for AP generation by delaying degradation of the first EPSP
Spatial: Long Lambda means signals that originate further from the initial segment can be summed. And less current will leak out once they reach the hillock.
These two forces work together.
Shunting Inhibition
Opening of Cl- Synapses on the cell body causes a small hyperpolarization and current outflow. More importantly, the open channels decrease membrane resistance, decreasing lambda and tau. Channels for shunting usually occur in the soma or dendritic branching sites. Triggering of excitatory and inhibitory cells at once here causes a smaller EPSP
Types of Receptors
Ionotropic: Ligand-Gated Ion Channel, direct ion flow and rapid Vm change.
Metabotropic: GPCRs, activates G protein as a second messenger, slower and more prolonged response.
Neurotransmitter Criteria
Must exist in presynaptic terminal, has to then be released from presynaptic terminal, then bind to postsynaptic receptors and cause some effect in the postsynaptic cell. This effect must change when steps in neurotransmission are affected, and a means must exist to remove and stop its effects.
Major types of Neurotransmitter
Amines (ACh, Dopamine, Norepinephrine, Epinephrine, 5-HT). Amino Acids (Glutamate, GABA, Glycine). Purines (ATP, Adenosine). Peptides (Endorphins), Gaseous NTs (Nitric Oxide).
General Scheme of Neurotransmission
Tripartite structure with presynaptic element, postsynaptic element, and astrocyte. 1. Precursor molecules are collected and synthesized into neurotransmitters via enzymatic reactions. 2. NTs are pumped into vesicles. 3. AP causes Ca2+ influx causing vesicles to fuse at precise spots in the active zone. 4. Neurotransmitters are released into the synaptic cleft. 5. Presynaptic autoreceptors modulate synthesis or release. 6. Termination via multiple methods.
Vesicular Pumps
Raising vesicular concentration of NT from micromolar to molar levels requires energetic transport. 2 types of pumps: proton pump loads vesicles with protons and specific transporters exchange them for a NT. Vesicles protect neurotransmitters from enzymes or oxidation.
