Summary of Neurotransmitters

The excitatory NT’s create a local depolarization (EPSP) and they activate it by opening ligand gated sodium ion channels. In the nervous system, however, there are other neurons that are inhibitory NT’s (IPSP) and when they activate a receptor site, instead of opening up a ligand gated sodium ion channel, it opens either a potassium ion channel or calcium ion channel and the inside of the cell becomes more negative (hyperpolarization).

We just went over ACh, glutamic acid and the catecholamines.

These catecholamines are all derived from the same amino acid tyrosine. When the catecholamine NT’s activate the receptor site, they don’t directly cause an opening of ligand-gated ion channels. They actually trigger adenylyl cyclase which converts ATP to cyclic AMP which increases the permeability of the ligand-gated sodium ion channels which leads to increased electrical activity in the cell. Cyclic AMP acts as a second messenger (intracellular messenger) and of course there must be an enzyme that breaks down this AMP otherwise it would continue to activate whatever it is doing for the rest of your life.

MAO breaks down the catecholamine neurotransmitters, however, since it’s the c-AMP that opens up the sodium ion channels, there is an enzyme called phosphodiesterase which breaks down the cyclic-AMP.

In summarizing, there are 3 different ways of mimicking the action of catecholamines:

• One is to give a mimetic (amphetamine and ephedrine),
• A second way is to use a drug called a MAO inhibitor which would prevent the catecholamines from breaking down and their effects would be prolonged or exaggerated.
• The third thing you could do is to give a drug called a phosphodiesterase inhibitor, such as caffeine, which prevents the cyclic-AMP from being broken down. These all have excitatory effects.

Nitric Oxide, a gas released from the synaptic knobs of some neurons causes blood vessels to dilate.

It’s obvious why we have excitatory NT’s, if we didn’t, nothing would happen. So why do we need inhibitory ones?

The first one is sleeping. We need inhibitory NT’s to ignore sensory input. When you go to sleep do your ears stop working and the answer is no, all your sensory neurons are continuously sending info to your brain and the only way you could go into this sleep state is to ignore all this information through the release of inhibitory neurotransmitters. It appears all vertebrate animals need sleep. The higher the level the more sleep they get. Which would make cats the most intelligence because they sleep 30 hours in 24 hours in a day.

Second role of inhibitory NT’s: it permits sensory discrimination and attention. Sensory overload leads to seizures. Epilepsy is due to over-excitation/stimulation of the brain. So if we don’t have inhibitory NT’s we go into seizures. This also comes up in the subject of ADD. So in ADD, a child or adult has trouble focusing on what’s important because they easily get distracted by other stimuli. They have no way of inhibiting the sensory input signals. They commonly could take medication and curiously they are stimulants. The stimulant drugs in your brain stimulate your brain to release inhibitory neurotransmitters.

A third reason why we have inhibitory NT’s is to give us fine motor control. In order for somebody to be a surgeon, dancer, musician, anything that involves precision, we not only activate somatic motor neurons, but simultaneously inhibit motor neurons to OTHER skeletal muscles. If somebody doesn’t have these inhibitory motor neurons their movements will be gross and exaggerated. An over stimulation of somatic motorneurons leads to convulsions. This is an over-excitation of skeletal muscles and is associated with epilepsy again.

We must clarify that there is a difference between convulsions and epilepsy.

• A seizure is too much input signal (no way of ignoring what’s coming in).
• A convulsion is too much motor output (too much excitation occurring going to the skeletal muscles).
• All epilepsy is associated with seizures but not all epilepsy is associated with convulsions.

As the brain develops as you go from an infant to a child to an adolescent to an adult, the brain develops and one of the things it’s developing is the release of inhibitory NT, so concentration and attention improves as we grow older. It’s not very important for a 3 year old to stay focused. Developmentally, movements of a child exhibit gross motor movements. As we grow we develop better fine motor movements. This kind of explains why ADD is developmentally related.

Another clinical considerations: Tetanus

Tetanus is caused by a bacterial infections (c. tetani; gram negative; produces exotoxins). These exotoxins interfere with inhibitory neurotransmitters and the result is seizures and convulsions. The reason tetanus is called “lock jaw” is because the muscles of the face are the ones that constrict first and when someone dies from it, it looks like a convulsion.