Table of Contents

Neurotransmitters

Brain cells communicate by signals transferred through chemicals released at one end of the connection and received at the other end. Brain cells are separated by a tiny gap between the endings of brancj of the neuron and the body or terminal of another neuron.

such chemicals are produced or synthesised from basic components in the brain itself and soon after doing their jobs, they are broken down to their components which are re-used for producing the same chemical again. In this way the constituent ingredients are not wasted unnecessarily.

there are many such chemicals in the brain and ouside it in the nervous system. they are called Neurotransmitters, as they are transmit the signal between neurons.

Four of these Neurotransmitters are widespread across the nervous system and play a major part in functions of the nervous system:

  • Dopamine
  • Serotonin
  • Acetycholine
  • Noradrenaline

Another important neurotransmitter is glutamate. Some of these neurotransmitter also act by controlling the release of another neurotransmitter as in the case of Dopamine controlling the release of Acetycholine and Serotonin controlling the release of Dopamine.

Dopamine

Dopamine is produced in specific dopaminergic neurons from its precursor tyrosine. tyrosine is transported into the neuron by an active transport pump and then converted into Dopamine by enzymes. tyrosine hydroxylase (TOH) produces DOPA (dihydroxyphenylanine) followed by DOPA decarboxylase which produce Dopamine.

Dopamine is destroyed by mono amine oxidase (MAO) and catechol-Of-methyl transferase (COMT). the enzymes involved in the synthesis and breakdown of Dopamine are also the same enzymes producing Noradrenaline and breaking it down.

Dopamine act on receptors at the cell body or axons of the neuroand. there are many types of Dopamine receptors, including at least five sub types and several different molecular isoforms.

There are four Dopamine pathways in the brain. the nigrostrial Dopamine pathway sends axons (projections) from substantia nigra to the basal ganglia and is involved in the movement control. the mesolimbic Dopamine pathway projects from midbrain ventral tegmental area to the nucleus accumbens, which is part of the limbic system of the brain, involved in behaviour, pleasurable sensations and both drug addiction and psychosis.

another pathway arise from the midbrain ventral tegmental area but send axons to the limbic cortex. this mesolimbic Dopamine pathway may have a role in psychosis and emotions.

the fourth Dopamine pathway is the tubero-infundibular pathway which is the projection from the hypothalamus tof the anterior pituitary gland and controls prolactin secretion.

Summary:

tyrosine —> tyrosine transporter –> inside the cell \ tyrosine —> tyrosine hydroxylase–> DOPA \ DOPA —> DOPA decarboxylase –> Dopamine \ Dopamine —→ MAO+COMT —>

Dopamine receptors : D1, D2, D3, D4, D5 \ Dopamine pathways : \ - Substantia nigra —> Basal ganglia (EPSE) \ - midbrain ventral tegmental area —>Nucleus accumbens \ - midbrain ventral tegmental area —>limbic cortex (psychosis) \ - Hypothalamus pathway —> anterior pituitary (Prolactin)

Serotonin

serotonin (5-hydroxytrytamine, 5-HT) is produced from the amino acid tryptophan which is transported to the neuron via a transport pump. tryptophan is converted into 5-hydroxytryptophan (5-HTP) by the enzyme tryptophan hydroxylase. tryptophan is then converted into 5-hydroxytrytamine by the enzyme aromatic amino acid decarboxylase. finally, serotonin is stored in synaptic vesicles until released by neuronal impulse by a selective transport pump. serotonin is destroyed by the enzyme mono amine oxidase.

serotonin receptors are subtyped depending on pharmacologic and molecular properties. the principal pre synaptic serotonin receptor is 5ht1d and there are several post synaptic serotonin receptors (5ht1a, 5ht2a, 5ht2c, 5ht3, 5ht4). \ there are at least five serotonin pathways in the central nervous system. serotonin pathways in the central nervous system starts from raphe nuclues in the midbrain. one pathway goes to the prefrontal cortex mediates cognitive effects, another pathway to basal ganglia mediates regulatory actions on movements and repetitive actions (OCD). the pathway from raphe to limbic cortex may mediate regulatory functions upon emotions, memory and anxiety. a pathway from raphe to the hypothalamus mediates eating behaviour and appetite. the pathway that projects down the spinal cord mediates sexual functioning. other pathways mediate control of serotonin at the sleep-wake cycle.

serotonin-dopamine projection to the basal ganglia:

serotonin neurons project to the basal ganglia from raphe nucleus in the midbrain. dopamine neurons from substatia nigra also project to basal ganglia. serotonin and dopamine neurons interact in the basal ganglia. serotonin neurons inhibit dopamine release in an axo-axonal synapses. 5HT receptors on pre synaptic dopamine axons terminals interact with serotonin which diffuse there from serotonin axons without a synapse.

acetycholine (ach) is a prominent neurotransmitter which is formed in cholinergic neurons from choline and acetyl co-enzyme A. choline is derived from dietary sources and acetyl co-enzyme A is made from glucose in the mitochondria of the neuron. choline acetyl transferase (CAT) is the enzyme which produce acetycholine. \ acetycholine is destroyed by acetycholine esterase ([[:wiki:psychiatry:ache|AChE]]) which convert acetycholine into choline which can be pumped back into the neuron by pre synaptic choline transporter.

there are two types of acetycholine receptors: nicotinic (N) and muscarinic (M) cholinergic receptors. muscarinic receptors include different sub types such as M1 M2 and Mx. M1 post synaptic receptors mediates the memory functions. there is a reciprocal relationship between dopamine and acetycholine in the nigrostrial dopamine pathway. dopamine normally suppresses acetycholine activity.

Glutamate:

glutamate or glutamic acid (Glu) is an amino acid which acts as a neurotransmitter, and also in protein synthesis. it is synthesised from glutamine by an enzyme in the mitochondria called glutaminase. glutamine itself can be obtained from glial cells adjacent to neurons. glial cells have structurally and metabolically. glutamate from metabolic pools in the glia is converted first to glutamine in the glial cells by the enzyme glutamatine synthetase, then glutamine is transported into the neuron for conversion into glutamate.

glutamate's actions are stopped by removal by two transport pumps. the first is a pre synaptic transporter and the second transporter pump is located on nearby glial cells. there is enzymatic breakdown.

there are several types of glutamate receptors including three that are linked to ion channels:NMDA (N-methyl-D-Aspartate), AMPA (Alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid) and Kainate. they are named after the agonists that selectively bind to them. another glutamate receptor is a G-protein linked receptor, which mediate long lasting electrical signals in the brain called "long-term potentiation" which have keyrole in the memory functions.

five sites on the NMDA (N-methyl-D-Aspartate) receptor modulate the NMDA-glutamate-calcium channel complex. the multiple receptors in and around such complex act together as allosteric modulatory sites. three of these are located around the NMDA (N-methyl-D-Aspartate) receptor : one is for the neurotransmitter glycine, another for polyamines and another for zinc. two of the modulatory sites are located inside or near the ion channel itself. magnesium can block the calcium channel at one of the these modulatory sites. the other inhibitory modulatory sites located inside the ion channel is sometimes called the pcp (phenycyclidine) binding sites.

normal excitatory functions of glutamate receptor NMDA (N-methyl-D-Aspartate) is ligand-gated ion channel. the glutamate causes the calcium channels to open and the neuron to be excited for neurotransmission.