Synaptic Transmission

chemical synapse:

  • a neurotransmitter is released from the presynaptic neuron and then diffuses to the post synaptic neuron. *Keynote: it diffuses across the synapse.

  • advantageous for complex decision making

  • Uses neurotransmitters to transmit information

Electrical synapse:

  • the neurons directly touch each other.

  • conduct impulses much faster, and most are bidirectional → can transmit impulses in either direction.

  • neurons are linked by gap junctions → allow relatively large substances pass between the cytoplasm of the two neurons.

  • passive current flow through gap junctions is instantaneous since neurotransmitters are not involved.

  • is simpler → what makes it fast, limits its function.

  • post synaptic neuron is neither stimulated or it is not

  • reactions are always the same in presynaptic and postsynaptic neurons

ex. If a presynaptic neuron has a depolarized reaction, so will the postsynaptic neuron

  • advantageous for rapid responses.

  • ALWAYS STIMULATORY

Neurotransmitters:

  • have delayed associated with their release mechanism

  • have a delay with their diffusion across the synapse

  • a delay binding and of opening of a channel on post synaptic neuron

  • modifiable

  • reactions made vary between neurons

  • there are far more neuropeptides than small molecule transmitters → when both are fired from the same axon terminal, it is called co-transmitters

  • to be considered a neurotransmitter a chemical must: 1. be synthesized and stored in a neuron, 2. released from the neuron when the neuron is stimulated, and the release mechanism must be calcium ion dependent, 3. there must be specific receptors present on the postsynaptic neuron that are activated in response to the neurotransmitter binding.

synaptic vesicles:

  • all over the axon terminal → one group near the plasma membrane facing the post synaptic neuron (clear-core vesicles) and the other found farther back from the plasma membrane (dense-core vesicles).

  • contain neurotransmitters

  • made up of a bilayer with several inserted proteins.

  • vesicles move to the active zone in order to fuse with the axon terminal plasma membrane

Active zones: several types of proteins→ what force the vesicle to exocytosis its contents into the synaptic space, inserted into the axon terminal’s membrane that gives the area the resemblance of a pyramid.

Synaptic cleft: gap between the pre- and post-synaptic neurons

  • contains structural proteins and is filled with extracellular fluid → where vesicles fuse through in order to reach the postsynaptic neuron.

Postsynaptic density: on post synaptic neuron, area directly beneath the axon terminal

Type 1 synapse “Gray’s Type 1 synapse”:

  • usually associated with EPSPs

  • has an asymmetrical distribution of proteins on the pre- and post- synaptic neurons

  • post synaptic neuron has far greater concentration of proteins than presynaptic neuron

  • usually excitatory

Type 2 synapse “Gray’s Type 2 synapse”:

  • has symmetrical distribution of proteins on the pre- and post- synaptic neurons

  • IPSPs predominate in this type

  • usually inhibitory

Chemical Synapse Overview

  • neurotransmitter must be synthesized and packaged into synaptic vesicle → it remains in that vesicle until the arrival of an action potential

  • A voltage gated calcium ion channel opens when an action potential reaches the axon terminal → this allows calcium ion to flow down their electrochemical gradient and reach axon terminal.

  • the binding of a neurotransmitter to its receptor after being released may cause either the opening or closing of an ion channel on the postsynaptic neuron.


Calcium:

  • calcium ion influx in axon terminal causes neurotransmitters to be released → the Ca2+ ions trigger a mechanism that causes the synaptic vesicles to be transported to the axon terminal plasma membrane where exocytosis of the neurotransmitter will occur.

  • Ca² ions trigger a signal transduction pathway: the process by which a signal (neurotransmitter; Ca ions) initiate a chain of molecular events that typically end with the activation of an enzyme → leading to a cellular response

  • the Ca ions activate/bind to calmodulin [calcium-modulated protein] → known as the calcium-calmodulin complex

Calcium-calmodulin complex

  • activates a protein Kinase: enzymes that transfer phosphate groups, primarily from ATP, to substrates.

  • Phosphorylates CaMKII

  • CaMKII phosphorylates synapsin: releases vesicles from the actin filaments, letting them move to the active zones where exocytosis occurs.

Exocytosis: SNARE proteins

  • Synaptobrevin and synaptotagmin are found on the synaptic vesicle

  • synaptotagmin: has the ability to bind calcium ions → causes the protein to insert utself into the plasma membrane of the axon terminal, is attached/anchored in the lipid bilayer of the synaptic vesicle [THE SNARE PROTEIN THAT FORCEFULLY CAUSES THE RELEASE OF NEUROTRANSMITTER INTO THE SYNAPTIC CLEFT]

  • Syntaxin and SNAP-25 are found in the axon terminal plasma membrane at active zones →resemble a pyramid

  • force the synaptic vesicle to merge with the axon terminal plasma membrane


Phosphorylated synapsin:

  • detaches the synaptic vesicle from the cytoskeleton, which then moves towards the active zone

Small molecule neurotransmitters:

  • Ach, dopamine, and serotonin.

  • called synaptic vesicles

  • produced by enzymes → the enzymes convert precursor molecules into the small molecule neurotransmitters

  • the enzyme is made in the nucleus and is moved down the neuron to the axon terminal where they produce the small molecule neurotransmitter

  • stored in small clear core synaptic vesicles → remain docked near the active zones

  • require less Ca ions to go in since they’re closer → low frequency stimulation needed

Neuropeptides:

  • Neuropeptide Y, oxytocin, substance P, CRF

  • called dense core vesicles or secretory granules

  • short proteins → they’re made up of amino acids linked together in some particular sequence → coding instructions to link these up are found in the DNA

  • made through transcription and translation → meaning they’re synthesized in the soma of the neuron

  • large dense core vesicles → found higher up in the axon terminal away from the active zones

  • require more Ca ions to go into the terminal in order to leave → requires high frequency of action potential

high frequency action potential

  • releases both types of transmitters

Low frequency action potentials

  • only releases small molecule transmitters

Types of synaptic arrangements:

  • axodendritic synapse: where an axon makes a synapse on a dendrite

  • axosomatic synapse: where an axon terminal synapses on the soma of another neuron → requires less neurotransmitter to fire an action potential in the target cell, since the synapse is closer to the axon hillock, decreasing the necessary distance traveled.

  • Axoaxonic synapse: where an axon synapses on other axons → requires the least amount of neurotransmitter to cause an action potential since the synapse has voltage gated sodium/potassium ion channels within it.


Neuropeptide synthesis (CRF):

  • released during high stress situations

  • stress neurotransmitter

  • CRF gene is found in the DNA in the nucleus

  • the gene is read to produce a CRF mRNA → ungoes transcription, then translation in Nissl bodies on ER

  • the CRF precursor travels to Golgi to undergo PTM→ Activates CRF

  • CRF then goes down to the terminal to await an AP

  • cycle repeats

  • Transcription factor used: c-Fos

  • c-fos moved to TATA sequence of CRF promotor and binds to it


Small molecules Neurotransmitter synthesis ( ACh)

  • ACh is synthesized by the combination of two precursor molecules → there is no transcription nor translation involved, and no gene exists for ACh

  • Choline acetyltransferase forms ACh in terminal

  • the enzyme doesn’t get packed into a vesicle until a molecular motor drags it into the terminal.