Once a neurotransmitter is released it will continue to activate receptors until it is scavenged either through active re-uptake or enzymatic degradation. While the brain is a pretty efficient scavenger of neurotransmitters it isn't perfect and neurotransmitters that aren't scavenged continue to randomly activate receptors and diffuse out of the synaptic cleft. A neurotransmitter that is part of an pulse is called phasic while a neurotransmitter that is awaiting degradation is called tonic.
It was surprising to me that these tonic neurotransmitters have an active role in the brain. Their random activation of receptors on the receiving neuron make it more sensitive, putting it on a hair trigger if you will. The random activation of auto-receptors on the sending neuron inhibit further neurotransmitter release. And when these tonic neurotransmitters diffuse out of the synaptic cleft they can sensitize other neurons nearby or even trigger cell death (in the case of glutamate)
The way that I like to think of it is that a phasic neurotransmitter carries an immediate signal while a tonic neurotransmitter carries a longer term record of phasic activity.
MAO and COMT are two important enzymatic pathways for enzymatic degradation. MAO degrades norepinephrine, serotonin and dopamine while COMT degrades norepinephrine and dopamine. COMT operates by attaching a methyl-donor to the neurotransmitter which is donated by SAM-E. With some consumer grade genetic testing I discovered that I had a defect in betaine homocysteine S-methyltransferase (BHMT) which is one pathway to recycle SAM-E. Supplemental TMG, also called betaine, simulated more BHMT activity for me.
My guess is that lower levels of SAM-E had the effect of elevating tonic dopamine and norepinephrine relative to serotonin by plugging one of the drains.
It was surprising to me that these tonic neurotransmitters have an active role in the brain. Their random activation of receptors on the receiving neuron make it more sensitive, putting it on a hair trigger if you will. The random activation of auto-receptors on the sending neuron inhibit further neurotransmitter release. And when these tonic neurotransmitters diffuse out of the synaptic cleft they can sensitize other neurons nearby or even trigger cell death (in the case of glutamate)
The way that I like to think of it is that a phasic neurotransmitter carries an immediate signal while a tonic neurotransmitter carries a longer term record of phasic activity.
MAO and COMT are two important enzymatic pathways for enzymatic degradation. MAO degrades norepinephrine, serotonin and dopamine while COMT degrades norepinephrine and dopamine. COMT operates by attaching a methyl-donor to the neurotransmitter which is donated by SAM-E. With some consumer grade genetic testing I discovered that I had a defect in betaine homocysteine S-methyltransferase (BHMT) which is one pathway to recycle SAM-E. Supplemental TMG, also called betaine, simulated more BHMT activity for me.
My guess is that lower levels of SAM-E had the effect of elevating tonic dopamine and norepinephrine relative to serotonin by plugging one of the drains.