What are neuron receptors?
When neurons want to communicate with each other, they use electrical and chemical signals to send messages. Let's elaborate on the analogy from the Synapse section of the Neuron Structure page, describing neuron communication as an email exchange. Neuron A wants to tell Neuron B something important. Neuron A (i.e., pre-synaptic neuron) sends an email to Neuron B (i.e., postsynaptic neuron) containing this important information. Neuron B receives the email in its inbox and reads it to know what steps to take next.
In this analogy, the email is a special ligand (e.g., neurotransmitter or hormone), and Neuron B's inbox where the email is received is a neuron receptor. More technically, a neuron receptor is a membrane protein that is triggered by a neurotransmitter/hormone. There are different types of neuron receptors.
Main Types of Receptors
Ligand-Gated Ion Channels
Ligands are molecules that bind to other molecules (e.g., neurotransmitter, hormone, drug). Ions are groups of atoms that are electrically charged (e.g., potassium, sodium). Ligand-gated ion channels, then, are receptors that allow ions to pass through the neuron membrane when a ligand binds to it. These receptors allow for speedy neuron communication.
Going back to our email analogy, Neuron A wants Neuron B to have more ions. So, it will send an email saying "Action!" telling Neuron B these instructions. Neuron B then knows to open its protein channel, letting ions flow into the cell.
Why would you want ions to flow into the cell? Well, remember that ions are electrically charged groups of atoms. Whether Neuron B will continue communication onto Neuron C depends on the electrical charge inside its membrane compared to the outside non-neuron space. A flow of ions into
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the neuron will change the electrical charge, or polarity, of the neuron. This change in polarity influenced whether the neuron will send a message to the next neuron.
G-Coupled Protein Receptors
G-protein coupled receptors (GPCRs) are the target for about 33% of all modern drugs. GPCRs do not work by direct binding of ligands to ion channels. Instead, they function through a structure, called a polypeptide, that is folded into 7 membranes, as well as a "G-protein complex." G-protein stands for guanine nucleotide binding protein.
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In GPCRs, a ligand binds to the 7-membrane polypeptide, rather than directly on the protein channel. This binding causes the shape of the 7-membrane polypeptide to change, waking up the G-protein complex.
Depending on the type of G-protein complex, neuron communication will happen in one of two ways: 1) cAMP signaling, 2) phosphatidylinositol signaling.
The signaling causes subunits of the G-protein complex to change what they are attached to. For certain GPCRs, signaling will also lead to the production of secondary messengers. With these changes in subunit binding and/or the release of secondary
messengers, ion channels will open. Then, ions will flow into the neuron, causing a change in the neuron's polarity, just as in ligand-gated ion channels.
Going back to the email analogy again, you can think of GPCRs as an email exchange between Neuron A and Neuron B, where Neuron B has an email assistant to help read through messages. This email assistant is the 7-membrane polypeptide who receives the email, then signals the orders to the G-protein complex, helping Neuron B decide whether to open the ion channel or not.
cAMP Signaling Pathway
What’s the best part of summer? Some would say camp, but I would say cAMP (aka cyclic adenosine monophosphate) 😬. Actually...cAMP is great any time of the year because it's important for lots of cell functions! cAMP is a secondary messenger, or molecule that helps relay information from a primary messenger in cell signaling.
To help explain the cAMP signaling pathway, let’s use an analogy of, you guessed it, summer camp. I’ll apologize for my cultural myopia now, given that this analogy centers on summer camp in the US and might not be so helpful if you were raised in another culture. First, let’s introduce the key players:
Primary Messenger (i.e., Ligand)
In cAMP signaling, primary messengers bind to G-protein coupled receptors to initiate cell activity. For our summer camp analogy, think of the primary messenger as the parent who wants to send his/her child off to camp.
In cAMP signaling, GPCRs are the type of receptor that a primary messenger binds to. For our summer camp analogy, think of the GPCR as the administrative staff of the cAMP. The G-protein (i.e., Gs) that is attached to a GPCR is like the camp director who learns information from the staff to ready the camp counselors.
Adenylyl cyclase is an enzyme that hangs out in the cell membrane. In cAMP signaling, its main role is to convert adenosine triphosphate (ATP) into cAMP. For our summer camp analogy, think of adenylyl cyclase as a camp counselor.
Adenosine Triphosphate (ATP)
ATP is a type of molecule called a nucleotide. This means it is one of the building blocks for nucleic acids (i.e., DNA/RNA). In cAMP signaling, it serves as a source of energy for the cell that
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ultimately gets converted into cAMP. For our summer camp analogy, think of ATP as children who are just about to get out of school for the summer. They have lots of stored up energy just waiting to be released!
cAMP is a secondary messenger that is converted from ATP by adenylyl cyclase. This messenger is the main star of the cAMP signaling pathway. For our analogy, I'll refer to these molecules as our camp attendees, or cAMPers.
Protein Kinase A
Our brains have only one type of target protein involved in the cAMP pathway. It is called protein kinase A and acts on additional proteins to produce a variety of cell functions once activated by cAMP. For our summer camp analogy, think of protein kinase A as camp cabins, so that each cabin participates in different activities.
How does cAMP signaling work?
First, a primary messenger binds to a GPCR. This is like a parent signing up his/her child for camp with the administrative staff. This binding causes the attached G-protein to break off and head over to adenylyl cyclase. In our camp analogy, the camp director needs to notify the counselor to get ready for the start of camp. Adenylyl cyclase can then convert ATP into cAMP, or our camp counselor helps our energetic students transition into cAMPers. Once converted into cAMP, the molecule binds to protein kinase A in order to activate the cell function. In our final part of the analogy, protein kinase A targets are like the cAMPers' cabins, which will determine the type of activities that follow. These activities include things like cell growth, cell specialization, gene transcription, or protein expression to help keep the cell healthy and communicating with other cells.
Phosphatidylinositol Signaling Pathway
Neuroplasticity has become popularized through programs that promise to "re-wire your brain," like Luminosity. Although the evidence supporting those programs is limited, the concept of neuroplasticity has a much more solid research basis.
Neuroplasticity is related to two processes called long-term potentiation (LTP) and long-term depression (LTD). They are important for memory and learning.
One way to think about how these functions lead to neuroplasticity is by thinking of them as a love story between Neuron A and Neuron B ♥️.
Think about LTP as the early stages of dating between two neurons, where both neurons are interested in making this thing happen. Let's say an action potential is like the text
messages that Neuron A sends to Neuron B. If the texts' signals are too weak for Neuron B to pick up on Neuron A's romantic interest, then the neurons ghost each other, and LTD happens.
Now let's say Neuron A and Neuron B are both super into dating each other. Neuron A sends a very clear text message about these feelings. Then, Neuron B knows it's worth going through LTP to form a long-lasting bond with Neuron A.
Glutamate is the major excitatory neurotransmitter. When glutamate binds to AMPA and NMDA receptors, Neuron B gets really excited about its pending relationship with Neuron A.
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First the AMPA receptor opens, letting in NA+ ions and depolarizing the neuron (i.e., Neuron B gets its hopes up). If its hopes are high enough via sufficient incoming NA+ ions, the Mg++ blocking the NMDA receptor is pushed out (i.e., Neuron B's doubts are gone and its heart is fully open to love with Neuron A).
With both receptors open, NA+ and Ca++ rush in the neuron, triggering protein kinases to phosphorylate Neuron B's AMPA receptors. Also, AMPA receptors that were hiding deep within Neuron B are brought to the cellular membrane, which encourages stronger and longer-lasting communication between Neuron A and Neuron B, the foundation of any good relationship.
Do neurons associated with grey and white brain matter communicate the same? Not completely. Whereas gray matter neurons have unmyelinated axons, white matter neurons get their lighter appearance thanks to myelin. The presence of myelin leads to differences in how action potentials, or cell signals, are sent along the neuron’s axon.
For unmyelinated axons, action potentials typically travel along the axon at a smooth and fairly continuous rate. For myelinated axons, action potentials move along the axon by jumping** between myelin sheath gaps, called nodes of Ranvier. This movement is called “saltatory conduction” – you might think of the word for jump in Spanish or Italian (i.e., saltar or saltare, respectively) to help you remember. Why does this difference in communication style matter? Speed of information. Along myelinated axons, nodes of Ranvier act like power-up stations where the action potential gets a little boost to travel to the next node. This boost comes from
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highly concentrated sodium ions at each node that charge the action potential.
How do these speeds differ? In actuality, about ~150 ms for unmyelinated axons compared to ~0.5-10 ms for myelinated axons. As an analogy, though, you can think about action potentials casually walking down a sidewalk for unmyelinated axons, and action potentials hoping down a long trampoline for myelinated axons. Saltatory conduction leads to faster and more reliable transmission, making them great for sending info long distances! . **technically not jumping, but very speedy travel under myelin gives the signal a jumping appearance.
 Bear, Connors, & Paradisio (2015). In Neuroscience: Exploring the Brain (4th edition)
 Banich & Compton (2018). In Cognitive Neuroscience (4th edition)
 Lovinger, D. M. (2008). Communication networks in the brain: neurons, receptors, neurotransmitters, and alcohol. Alcohol Research & Health.
 Alexander, S. P. H., Mathie, A., & Peters, J. A. (2011). Ligand‐gated ion channels. British Journal of Pharmacology, 164, S115-S135.
 Smrcka, A. V. (2008). G protein βγ subunits: central mediators of G protein-coupled receptor signaling. Cellular and molecular life sciences, 65(14), 2191-2214.
 González-Espinosa, C., & Guzmán-Mejía, F. (2014). Basic Elements of Signal Transduction Pathways Involved in Chemical Neurotransmission. In Identification of Neural Markers Accompanying Memory (pp. 121-133).
 Serezani, C. H., Ballinger, M. N., Aronoff, D. M., & Peters-Golden, M. (2008). Cyclic AMP: master regulator of innate immune cell function. American journal of respiratory cell and molecular biology, 39(2), 127-132.
 Siegel, G. J. (1999). Basic neurochemistry: molecular, cellular and medical aspects (No. V360 SIEb).
 Neishabouri, A., & Faisal, A. A. (2014). Saltatory conduction in unmyelinated axons: clustering of Na+ channels on lipid rafts enables micro-saltatory conduction in C-fibers. Frontiers in neuroanatomy, 8, 109.
 Wen, Q., & Chklovskii, D. B. (2005). Segregation of the brain into gray and white matter: a design minimizing conduction delays. PLoS computational biology, 1(7), e78.
 Purves, D., Augustine, G. J., Fitzpatrick, D., Katz, L. C., LaMantia, A. S., McNamara, J. O., & Williams, S. M. (2001). Increased conduction velocity as a result of myelination. Neuroscience.
 Kuriscak, E., Trojan, S., and Wunsch, Z. (2002). Model of spike propagation reliability along the myelinated axon corrupted by axonal intrinsic noise sources. Physiol. Res. 51, 205–215.
 Hodgkin, A. L., and Huxley, A. F. (1952). A quantitative description of membrane current and its application to conduction and excitation in nerve. J. Physiol. 117, 500–544.