Neuro Transmitter

What is a synapsis

Neurons have specialized projections called dendrites and axons. Dendrites bring information to the cell body and axons take information away from the cell body. Information from one neuron flows to another neuron across a synapse. The synapse is a small gap separating 2 neurons. The synapse consists of: 1. a presynaptic ending that contains neurotransmitters, mitochondria and other cell organelles, 2. a postsynaptic ending that contains receptor sites for neurotransmitters and, 3. the synaptic cleft: a space between the presynaptic and postsynaptic endings

The Synapse

Junction between two cells Site where action potentials in one cell cause action potentials in another cell Types Presynaptic Postsynaptic

Electrical Synapses Gap junctions that allow local current to flow between adjacent cells Found in cardiac muscle and many types of smooth

Chemical Synapses

Components Presynaptic terminal Synaptic cleft Postsynaptic membrane Neurotransmitters released by action potentials in presynaptic terminal Synaptic vesicles Diffusion Postsynaptic membrane Neurotransmitter removal

More about synapsis For communication between neurons to occur, an electrical impulse must first travel down an axon to the synaptic terminal

Neurotransmitter Mobilization and Release Here at the synaptic terminal (the presynaptic ending), the electrical impulse will trigger the migration of vesicles (the red dots in the figure to the left) containing neurotransmitters toward the presynaptic membrane. The vesicle membrane will fuse with the presynaptic membrane releasing the neurotransmitters into the synaptic cleft. Until recently, it was thought that a neuron produced and released only one type of neurotransmitter. This was called "Dale's Law." However, there is now evidence that neurons can contain and release more than one kind of neurotransmitter.

Synapsis Diffusion of Neurotransmitters Across the Synaptic Cleft The neurotransmitter molecules then diffuse across the synaptic cleft where they can bind with receptor sites on the postsynaptic ending to influence the electrical response in the postsynaptic neuron. In the figure on the right, the postsynaptic ending is a dendrite (axodendritic synapse), but synapses can occur on axons (axoaxonic synapse) and cell bodies (axosomatic synapse). When a neurotransmitter binds to a receptor on the postsynaptic side of the synapse, it results in a change of the postsynaptic cell's excitability: it makes the postsynaptic cell either more or less likely to fire an action potential. If the number of excitatory postsynaptic events are large enough, they will add to cause an action potential in the postsynaptic cell and a continuation of the "message." Many psychoactive drugs and neurotoxins can change the properties of neurotransmitter release, neurotransmitter reuptake and the availability of receptor binding sites.

Neurotransmitters and neuropeptides Communication of information between neurons is accomplished by movement of chemicals across a small gap called the synapse. Chemicals, called neurotransmitters, are released from one neuron at the presynaptic nerve terminal. Neurotransmitters then cross the synapse where they may be accepted by the next neuron at a specialized site called a receptor. The action that follows activation of a receptor site may be either depolarization (an excitatory postsynaptic potential) or hyperpolarization (an inhibitory postsynaptic potential). A depolarization makes it MORE likely that an action potential will fire; a hyerpolarization makes it LESS likely that an action potential will fire.

Postsynaptic Potentials

Excitatory postsynaptic potential (EPSP) Depolarization occurs and response is stimulatory Depolarization might reach threshold producing an action potential and cell response Inhibitory postsynaptic potential (IPSP) Hyperpolarization and response is inhibitory Decrease action potentials by moving membrane potential farther from threshold

Nerotransmitters and Neuromodulators Neurotransmitter ….Any specific chemical agent released by a presynaptic cell on excitation that crosses the synaptic cleft and stimulates or inhibits the postsynaptic cell some neurons can secrete more than one type of neurotransmitter Neuromodulators ….Are chemical substances released from neurons that can presynaptically or postsynaptically influence the likelihood that an action potential in the presynaptic terminal wall result in the production of action potential in the postsynaptic cell.

Neurotransmitters etc. Discovery of Neurotransmitters Back in 1921, an Austrian scientist named Otto Loewi discovered the first neurotransmitter. In his experiment (which came to him in a dream), he used two frog hearts. One heart (heart #1) was still connected to the vagus nerve. Heart #1 was placed in a chamber that was filled with saline. This chamber was connected to a second chamber that contained heart #2. So, fluid from chamber #1 was allowed to flow into chamber #2. Electrical stimulation of the vagus nerve (which was attached to heart #1) caused heart #1 to slow down. Loewi also observed that after a delay, heart #2 also slowed down. From this experiment, Loewi hypothesized that electrical stimulation of the vagus nerve released a chemical into the fluid of chamber #1 that flowed into chamber #2. He called this chemical "Vagusstoff". We now know this chemical as the neurotransmitter called acetylcholine.

Criteria for neurotransmitters Neuroscientists have set up a few guidelines or criteria to prove that a chemical is really a neurotransmitter. Not all of the neurotransmitters that you have heard about may actually meet every one of these criteria. •The chemical must be produced within a neuron. •The chemical must be found within a neuron. •When a neuron is stimulated (depolarized), a neuron must release the chemical. •When a chemical is released, it must act on a post-synaptic receptor and cause a biological effect. •After a chemical is released, it must be inactivated. Inactivation can be through a reuptake mechanism or by an enzyme that stops the action of the chemical. •If the chemical is applied on the post-synaptic membrane, it should have the same effect as when it is released by a neuron.

Types of neurotransmitters There are many types of chemicals that act as neurotransmitter substances. Below is a list of some of them. •Small Molecule Neurotransmitter Substances Acetylcholine (ACh) Serotonin (5-HT)

Dopamine (DA)

Histamine

Norepinephrine (NE)

Epinephrine

•Amino Acids Gamma-aminobutyric acid (GABA) Aspartate

Glycine Glutamate

Types of neurotransmitters •Neuroactive Peptides - partial list!! bradykinin

beta-endorphin

bombesin calcitonin

cholecystokinin

enkephalin

dynorphin

gastrin

substance P

secretin somatostatin

neurotensin motilin

oxytocin prolactin thyrotropin

insulin

glucagon

vasopressin angiotensin II

sleep peptides galanin neuropeptide Y thyrotropin-releasing hormone gonadotropnin-releasing hormone growth hormone-releasing hormone luteinizing hormone vasoactive intestinal peptide •Soluble Gases Nitric Oxide (NO) Carbon Monoxide

Transport and release of neurotransmitters Neurotransmitters are made in the cell body of the neuron and then transported down the axon to the axon terminal. Molecules of neurotransmitters are stored in small "packages" called vesicles (see the picture on the right). Neurotransmitters are released from the axon terminal when their vesicles "fuse" with the membrane of the axon terminal, spilling the neurotransmitter into the synaptic cleft.

Unlike other neurotransmitters, nitric oxide (NO) is not stored in synaptic vesicles. Rather, NO is released soon after it is produced and diffuses out of the neuron. NO then enters another cell where it activates enzymes for the production of "second messengers."

Binding and inactivation of neurotransmitters Receptor Binding Neurotransmitters will bind only to specific receptors on the postsynaptic membrane that recognize them Inactivation of Neurotransmitters The action of neurotransmitters can be stopped by four different mechanisms 1. Diffusion: the neurotransmitter drifts away, out of the synaptic cleft where it can no longer act on a receptor.

Inactivation of neurotransmitters 2. Enzymatic degradation (deactivation): a specific enzyme changes the structure of the neurotransmitter so it is not recognized by the receptor. For example, acetylcholinesterase is the enzyme that breaks acetylcholine into choline and acetate. 3. Glial cells: astrocytes remove neurotransmitters from the synaptic cleft 4. Reuptake: the whole neurotransmitter molecule is taken back into the axon terminal that released it. This is a common way the action of norepinephrine, dopamine and serotonin is stopped...these neurotransmitters are removed from the synaptic cleft so they cannot bind to receptors

Neurotransmitter Removal

Spatial and Temporal Summation Spatial summation ….Summation of the local potentials in which two or more action potentials arrive simultaneously at two different presynaptic terminals that synapse with the same postsynaptic neuron Temporal summation …Summation of the local potential that results when two or more action potentials arrive in very close succession at a single presynaptic terminal

Summation Spatial Summation Combination of spatial and temporal summation

Temporal Summation