The process begins when a population of synaptic vesicles become “docked” against the presynaptic membrane, ready to release their neurotransmitter into the synaptic cleft

Docking is accomplished when clusters of protein molecules attach to other protein molecules located in the presynaptic membrane.

The release zone of the presynaptic membrane contains voltage-dependent calcium channels. When the membrane of the terminal button is depolarized by an arriving action potential, the calcium channels open.

Ca is located in highest concentration in the extracellular fluid. Thus, when the voltage-dependent calcium channels open, Ca flows into the cell, propelled by electrostatic pressure and the force of diffusion.

The entry of Ca is an essential step; if neurons are placed in a solution that contains no calcium ions, an action potential no longer causes the release of the neurotransmitter.

Calcium ions that enter the terminal button bind with the clusters of protein molecules that join the membrane of the synaptic vesicles with the presynaptic membrane.

This event makes the segments of the clusters of protein molecules move apart, producing a fusion pore—a hole through both membranes that enables them to fuse together.

There are three distinct pools of synaptic vesicles

1. Release-ready vesicles are docked against the inside of the presynaptic membrane, ready to release their contents when an action potential arrives. These vesicles constitute less than 1 percent of the total number found in the terminal.

2. Recycling pool vesicles constitute 10–15 percent of the total pool of vesicles

3. Reserve pool vesicles make up the remaining 85–90 percent

Low rate of axon fire = Only release of ready vesicles

High rate of axon fire = Vesicles from the recycling pool and reserve pool will release their contents.

After the release of neurotransmitter, the vesicles in the

1. Ready-release pool use a process known as kiss and run. These synaptic vesicles release most or all of their neurotransmitter, the fusion pore closes, and the vesicles break away from the presynaptic membrane and get filled with neurotransmitter again.

2. Recycling pool vesicles merge and recycle and consequently lose their identity. The membranes of these vesicles merge with the presynaptic membrane. Little buds of membrane then pinch off into the cytoplasm and become synaptic vesicles. The appropriate proteins are inserted into the membrane of these vesicles, and the vesicles are filled with molecules of the neurotransmitter.

3. Reserve pool vesicles are recycled through a process of bulk endocytosis. Large pieces of the membrane of the terminal button fold inward, break off, and enter the cytoplasm. New vesicles are formed from small buds that break off of these pieces of membrane.

The neurotransmitters start by diffusing across the synaptic cleft and attaching to the binding sites of special protein molecules located in the postsynaptic membrane, called postsynaptic receptors.

Once binding occurs, the postsynaptic receptors open neurotransmitter-dependent ion channels, which permit the passage of specific ions into or out of the cell.

2 ways neurotransmitters open ion gates

1. Direct/ Ionotrophic Receptor: When a molecule of the appropriate neurotransmitter attaches to it, the ion channel opens. The are faster than metabotrophic receptors.

2. Indirect/ Metabotrophic Receptors: Involve steps that require the cell expend metabolic energy. Metabotropic receptors are located in close proximity to another protein attached to the membrane—a G protein. When a molecule of the neurotransmitter binds with the receptor, the receptor activates a G protein situated inside the membrane next to the receptor. When activated, the G protein activates an enzyme that stimulates the production of a chemical called a second messenger. Molecules of the second messenger travel through the cytoplasm, attach themselves to nearby ion channels, and cause them to open

There are four major types of neurotransmitter-dependent ion channels are found in the postsynaptic membrane: sodium (Na+), potassium (K+), chloride (Cl-), and calcium (Ca+).

The neurotransmitter-dependent sodium channel is the most important source of excitatory postsynaptic potentials.

• The sodium–potassium transporters keep sodium outside the cell, waiting for the forces of diffusion and electrostatic pressure to push it in. Obviously, when sodium channels are opened, the result is a depolarization—an excitatory postsynaptic potential (EPSP).

K+ is positively charged, its efflux will hyperpolarize the membrane, producing an inhibitory postsynaptic potential (IPSP).

• The sodium–potassium transporters maintain a small surplus of potassium ions inside the cell. If potassium channels open, some of these cations will follow this gradient and leave the cell.

The effect of opening chloride channels depends on the membrane potential of the neuron.

• At many synapses, inhibitory neurotransmitters open the chloride channels, instead of (or in addition to) potassium channels.

• If the membrane is at the resting potential, nothing happens, because the forces of diffusion and electrostatic pressure balance perfectly for the chloride ion.

• However, if the membrane potential has already been depolarized by the activity of excitatory synapses located nearby, then the opening of chloride channels will permit Cl2 to enter the cell. The influx of anions will bring the membrane potential back to its normal resting condition. Thus, the opening of chloride channels serves to neutralize EPSPs.

• Calcium ions (Ca2+), being positively charged depolarizes the membrane, producing EPSPs

Postsynaptic potentials are brief depolarizations or hyper polarizations caused by the activation of postsynaptic receptors with molecules of a neurotransmitter.

They are kept brief by two mechanisms: Reuptake and Enzymatic deactivation. The postsynaptic potentials produced by most neurotransmitters are terminated by reuptake.

Reuptake is the re-entry of a neurotransmitter just liberated by a terminal button back through its membrane, thus terminating the postsynaptic potential.

This process is simply an extremely rapid removal of neurotransmitter from the synaptic cleft by the terminal button.

The membrane contains special transporter molecules that draw on the cell’s energy reserves to force molecules of the neurotransmitter from the synaptic cleft directly into the cytoplasm.

When an action potential arrives, the terminal button releases a small amount of neurotransmitter into the synaptic cleft and then takes it back, giving the postsynaptic receptors only a brief exposure to the neurotransmitter.

Enzymatic deactivation is accomplished by an enzyme that destroys molecules of the neurotransmitter.

Postsynaptic potentials are terminated in this way for acetylcholine (ACh) and for neurotransmitters that consist of peptide molecules.

Transmission at synapses on muscle fibers and at some synapses between neurons in the central nervous system is mediated by ACh.

Postsynaptic potentials produced by ACh are short lived because the postsynaptic membrane at these synapses contains an enzyme called acetylcholinesterase (AChE). AChE destroys ACh by cleaving it into its constituents: choline and acetate. Because neither of these substances is capable of activating postsynaptic receptors, the postsynaptic potential is terminated once the molecules of ACh are broken.

Excitatory postsynaptic potentials increase the likelihood that the postsynaptic neuron will fire; inhibitory postsynaptic potentials decrease this likelihood.

“Firing” refers to the occurrence of an action potential.

The rate at which an axon fires is determined by the relative activity of the excitatory and inhibitory synapses on the soma and dendrites of that cell.

If there are no active excitatory synapses or if the activity of inhibitory synapses is particularly high, that rate could be close to zero.

The interaction of the effects of excitatory and inhibitory synapses on a particular neuron is called neural integration. (Integration means “to make whole,” in the sense of combining two or more functions.)

The process when several excitatory synapses become active:

• The release of the neurotransmitter produces depolarizing EPSPs in the dendrites of the neuron.

• These EPSPs (represented in red) are then transmitted down the dendrites, across the soma, to the axon hillock located at the base of the axon.

• If the depolarization is still strong enough when it reaches this point, the axon will fire.

The process when inhibitory synapses become active at the same time:

• Inhibitory postsynaptic potentials are hyperpolarizing, they bring the membrane potential away from the threshold of excitation.

• They tend to cancel the effects of excitatory postsynaptic potentials.

If the activity of excitatory synapses goes up, the rate of firing will go up. If the activity of inhibitory synapses goes up, the rate of firing will go down.

Neurotransmitters are released by terminal buttons of neurons and bind with receptors in the membrane of another cell located a very short distance away.

Neuromodulators are chemicals released by neurons that travel farther and are dispersed more widely than are neurotransmitters.

Neuromodulators are secreted in larger amounts and diffuse for longer distances, modulating the activity of many neurons in a particular part of the brain.

Neuromodulators affect general behavioral states such as vigilance, fearfulness, and sensitivity to pain.

Neuromodulators can be packaged into vesicles and released by neurons, secreted as hormones and delivered through the circulatory system.

Hormones are secreted by cells of endocrine glands or by cells located in various organs, such as the stomach, the intestines, the kidneys, and the brain.

Cells that secrete hormones release these chemicals into the extracellular fluid. The hormones are then distributed to the rest of the body through the blood stream.

Hormones affect the activity of cells that contain specialized receptors located either on the surface of their membrane or deep within their nuclei.

Cells that contain receptors for a particular hormone are referred to as target cells for that hormone; only these cells respond to its presence.

Many neurons contain hormone receptors, and hormones are able to affect behavior by stimulating the receptors and changing the activity of these neurons. (Testosterone, increases the aggressiveness of most male mammals.

Steroid hormones:

• They consist of very small fat-soluble molecules.

• Steroid hormones include the sex hormones secreted by the ovaries and testes and the hormones secreted by the adrenal cortex.

• Steroid hormones are soluble in lipids, they pass easily through the cell membrane.

• They travel to the nucleus, where they attach themselves to receptors located there. The receptors, stimulated by the hormone, then direct the machinery of the cell to alter its protein production.

• Investigators have discovered the presence of steroid receptors in terminal buttons and around the postsynaptic membrane of some neurons.

• These steroid receptors influence synaptic transmission, and they do so rapidly.