Psychiatry Lecture 2 U0

Neurotransmitters The brain should be seen as an information processor. How the brain communicates: Fundamental concepts: o The neuron o The synapse (synaptic cleft) The space between the transmitting neuron (pre-synaptic neuron) and the receiving neuron (post-synaptic neuron). o The production of the electron signal: Electron signal is transmitted down the axon of a neuron and then go down all the terminal synapses of the axon. Loewi discovered the mechanisms of neurotransmitters of the synapses. He believed that a chemical signal is sent between neurons and transformed into electrical signals in the post-synaptic neuron. Performed an experiment: It was known at the time that neurons dont just synapsed on other neurons, but also other organs. Dissects the hearts of two frogs. Put one heart in a saline solution. One heart had the nerves remaining, while the other heart was completely dissected. He stimulated the vagus nerve (a nerve that, when stimulated, will slow down the heart) and viewed a slowed effect. He transferred some of the chemicals diffused in the fluid of the first beaker into the second beaker. The second heart undergone the same effects as the first heart. Won the Nobel Prize in 1936 for this scientific finding. He was an Austrian Jew and was forced to give up his Nobel Prize money for his escape from Germany. o Neurotransmission: When the action potential reaches the terminal region, it causes an influx of calcium to enter the cell. Calcium sits in the fluid that surrounds the neurons. Electrically charged gates allow calcium ions to come into the cell. It binds to the vesicles of the neurons. The vesicles merges with the terminal membrane and allows the transmitters to come out and bind with receptors. Once the transmitter binds with the receptor, the next cell will pass on another electrical charge. o Two types of neuron messages: Short term messages (controlled by the proteins: Ionophores)

Psychiatry Lecture 2 U0
Very simple messages. Tells the receiving neurons to generate its own action potentials or to inhibit the next action potential. Excitatory vs Inhibitory (Binary in nature) Complicated transmissions can be created by grouping numerous neurons together. RESISTENT to misinterpretation! (Yes or No, no maybes) Long term messages (Second messengers) Takes almost days or months to interpret. Messages that tell the neurons to build or shut down manufacturing of receptors and neurons. A building process rather than transmission processes. Metabolic messages o Work more o Work Less Genetic messages: o Activate expressions of one or more genes Message I: Receptors coupled to ionophores: Receptors that, once coupled with ionophores, will permit the flow of ions. Ionophores are the channels through hwhich the ions can flow. Ionophores are specific to each type of ion. Once a neurotransmitter molecule attaches to a receptor, the ionophore channel will open, allowing specific ion spcies to enter or exit the cell. This will cause the inner cellular membrane to change in charge, which may excite or inhibit the axon. Inhibition will make it more difficult to generate an action potential. Important three ions: Aqueous sodium Na+ Aqueous potassium K+ Aqueous chloride Cl Normally in a resting neuron, there are a large quantity of Na+ ions outside the neuron, K+ inside the neuron, Cl- outside the neuron. Action potential at a synapse: When there is no transmitter bound to the ionophore, it is closed When the receptor binds, it opens the ionophore gate. It allows sodium to enter the cell and excites the cell. When a transmitter binds to a receptor, it allows potassium to move outside the cell. When potassium leaves the cell, you get inhibition. When a transmitter binds to a chloride ionophore, chloride can enter the cell and will further inhibit the cell. Excitation: when the inside of the cell becomes more positive.

Psychiatry Lecture 2 U0
When one section of the neuron becomes sufficiently positive, then it opens up (not transmitter related) channels down the axon of the cell. So on and so forth. o Inhibition: when the inside of the cell becomes more negative. o Many toxins in humans work by clogging up the channels of the neurons. Message II: Second Messengers: o Some receptors, instead of being coupled with channels, are coupld with second messengers which are activation/inhibition PROTEINS inside the cell that will alter the functions of the cell. o Once coupled, they will change the sensitivity of the cell, or change gene expression. o This can be down by freeing genetic enzymes/proteins that are bound closely to inactivated receptors. This protein can turn on other components of the cell and activate gene expression. One example of this protein is adenylyl cyclase. This protein can produce cAMP (cyclic adenosine monophosphate) is an example of a second messenger. It can lock other receptors by attaching a phosphate group to a receptor. Alternatively, it can enter the nucleus and activate or inhibit a gene. Inhibition and Excitation Transmitters: o There are multiple receptor types for every transmitter. o Subtypes of receptors will be coupled with specific ionophores/second messenger. o Seratonin has 14 receptors that can have different results in the presence of serotonin. Connected to different ionophores and different second messengers. o Caffeine is a promoter of many second messenger processes, including cAMP. o Theophylline is contained in tea and it is a more potent promoter. Special type of communication: The autoreceptor: o Located on the PRE-synaptic neuron. o Respond to the very transmitter of the own neurons. o They are generally inhibitory. They will cause the neuron that send the signal to slow down their chemical signals. An evolutionary mechanism that acts as a failsafe and prevents neurons from always releasing transmitters. o They prevent the neuron from using all of its transmitter molecules. A determinant of effective communication. o As long as the transmitter is bound to the receptor, the message will be given and the channels will remain open. o Normally, the transmitters will dissociate from the receptors and remain in the synaptic cleft o If left there, it will rebind and unbind repeatedly. The coupling and recoupling problem. o Two mechanisms to terminate the message: Degradation (catabolism)

Psychiatry Lecture 2 U0
Catabolism is the breakdown of neurotransmitters in the synaptic cleft by a chemical enzyme. Deactivated transmitters that are broken are called metabolites. To check for how activate a specific transmitter was, measurements of the metabolites can be helpful. Back in the 1900s, metabolites were measured in the urine. Enzymes all end in the suffix ase. Reuptake Reuptake pump exists on the PRE-synaptic neuron. In the presence of neurotransmitters, it will reuptake the used neurotransmitters and re-envelope the transmitters via vesicles.