Education: Neurotransmitters

We have been talking about the Human Connectome Project which aims map the nerve connections of the human brain. But to understand what they do we have also to be aware what each nerve does. Is it a stimulatory (excitatory) nerve? an inhibitor nerve? or a dis-inhibitory nerve?-inhibits a negative signal and so is excitatory) this is determined by the Neurotransmitters that they make and respond to. This adds to the complexity of understanding of the network of nerves

Neurotransmitters are natural chemicals that transmit signals from a neuron (nerve foot process) to a target nerve (head process=dendrite) across a synapse (gap between nerves) Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane in the axon terminal (nerve foot process), on the pre-synaptic side(nerve before the synapse) of a synapse. They are released into and diffuse across the synaptic cleft (space between the nerves) , where they bind to specific receptors in the membrane on the post-synaptic side (nerve on the other side of the synapse) of the synapse. Release of neurotransmitters usually follows arrival of an action potential (nerve impulse) Neurotransmitters are synthesized from plentiful and simple precursors, which are readily available from the diet and which require only a small number of biosynthetic steps to convert.

There are many different neurotransmitters and includes some amino acids such as glutamate, aspartate, D-serine, gamma-aminobutyric acid (GABA), glycine. There are  over fifty different neuroactive peptides and there are monoamines and other biogenic amines such as dopamine, noradrenaline(American=norepinephrine); adrenaline (American=epinephrine), histamine, serotonin. Other neurotransmitters included molecules such as acetylcholine (ACh). 

The action of a neurotransmitter is to activate a receptor. Therefore, the effects of a neurotransmitter system depend on the connections of the neurons that use the transmitter, and the chemical properties of the receptors that the transmitter binds to.

Glutamate is used at the great majority (~90%) of fast excitatory synapses in the brain and spinal cord. It is also used at most synapses that are "modifiable", i.e. capable of increasing or decreasing in strength. Modifiable synapses are thought to be the main memory-storage elements in the brain. Excessive glutamate release can lead to excitotoxicity causing cell death. 

GABA is used at the great majority of fast inhibitory synapses in virtually every part of the brain. Many sedative/tranquilizing drugs act by enhancing the effects of GABA such as baclofen. Correspondingly glycine is the inhibitory transmitter in the spinal cord. 

Acetylcholine is distinguished as the transmitter at the neuromuscular junction connecting motor nerves to muscles. Acetylcholine also operates in many regions of the brain, but using different types of receptors

Dopamine has a number of important functions in the brain. It plays a critical role in the reward system, and control of motor co-ordination in the basal ganglia

Serotonin is a monoamine neurotransmitter. Most is produced by and found in the intestine (approximately 90%), and the remainder in central nervous system neurons. It functions to regulate appetite, sleep, memory and learning, temperature, mood, behaviour, muscle contraction, and function of the cardiovascular system and endocrine (Hormone) system 

Substance P is a neuropeptide responsible for transmission of pain from certain sensory neurons in the peripheral nervous system to the central nervous system.
Neurons expressing certain types of neurotransmitters sometimes form distinct systems, where activation of the system affects large parts of the brain, called volume transmission. Major neurotransmitter systems include the noradrenaline (norepinephrine) system, the dopamine system, the serotonin system and the cholinergic system.

I don't understand the complexity of all this and so don't worry if you don't understand it too!The take-home message is that this is all very complex and unravelling it, means that there is a difficult task ahead.

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