1. Neurotransmitters
Domina Petric, MD

2. Neurotransmitters classes
small molecule neurotransmitters
peptide neurotransmitters

3. Receptor classes
Ionotropic receptors: receptors on ligand-gated ion channels.
Metabotropic receptors: activate second-messenger system.

4. Interaction with receptors
Small molecule neurotransmitters can interact with both ionotropic receptors and metabotropic receptors.
Small molecules are associated with quick actions.
Peptide neurotransmitters only interact with metabotropic receptors.
Metabotropic receptors mediate slower and potentially longer lasting effects in postsynaptic neurons.

5. Small molecule neurotransmitters aminoacids:
glutamate
aspartate
GABA
glycine

6. Small molecule neurotransmitters
When they interact with ionotropic receptors, they have quick effect.
Interacting with metabotropic receptors they produce longer lasting effect.

7. Glutamate It is the major excitatory neurotransmitter in the CNS.
It is involved in various aspects of cellular metabolism.
It is also concentrated in synaptic vesicles at the terminals of neurons that use glutamate as neurotransmitter.

8. GABA (gama-aminobutyric acid) and glycine
GABA is a metabolite of glutamate.
GABA and glycine have inhibitory role in mature nervous system.
GABA is the most important transmitter in the brain that mediates synaptic inhibition.
Glycine is very important neurotransmitter in spinal cord especially for synaptic inhibition.
Glycine serves as co-transmitter in synapses that release glutamate: binding of glycine is important for the activity of one type of glutamate receptor.

9. Acetylcholine
It is small molecule neurotransmitter, but not an amino acid.
Outside the CNS it is major excitatory neurotransmitter of human somatic motor neurons.
It is released on muscle fibre leading to the contraction of muscles.
It is also a major excitatory neurotransmitter in autonomic ganglia.
It is the neurotransmitter of many postganglionic parasympathetic fibres.

10. Acetylcholine
Within the brain acetylcholine has an important modulatory role that may be important in various cognitive functions (for example attention).

11. Small molecules neurotransmitters biogenic amines
dopamine
norepinephrine
epinephrine
serotinin
histamine
Biogenic amines modulate the function of neuronal circuits.

12. Biogenic amines
Those are very important in motivation and reward systems.
Dopamine is critical for modulating movement in circuits such as basal ganglia.
Dopamine is involved in activation of circuits in the prefrontal cortex (mediates various aspects of cognition).
Norepinephrine is also very important in cognitive functioning (for example attention).

13. Dopamine
Dopamine is derived from cells with cell bodies in midbrain: substantia nigra (pars compacta) and ventral tegmental areas.
Cells from substantia nigra are sending their axons to the striatum.
Cells from the ventral tegmental areas are sending their axons into medial temporal lobe structures (for example amygdala) and to the ventral and medial aspects of prefrontal cortex.

14. Striatum
Neuroscientificallychallenged.com

15. Ventral tegmental area
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Ventromedial
prefrontal
cortex
Ventral tegmental area
Neuroscientificallychallenged.com
Knowingneurons.com

16. Norepinephrine
Derived from cells with cell bodies in the dorsal part of the pons: locus coeruleus.
These cells are sending their axons everywhere in the CNS including the spinal cord.

17.
Counselheal.com
Locus coeruleus

18. Serotonin
Comes from a group of cells found in different areas of the brainstem: the seam nuclei (Raphe nuclei).
Bethopedia.com

19. Neuropeptides (peptide neurotransmitters)
Larger molecules: usually 3-30 amino acids long, but can be more than 100 amino acids long.
Enkephalins are opioids that have analgesic effects in the brain, they bind to receptors in various places including the spinal cord.
Substance P is very important in modulating the transmission of pain signals in the dorsal horn of the spinal cord.

20. Neuropeptides (peptide neurotransmitters)
Many of hypothalamic releasing hormones are neuropeptides.

21. Unconventional neurotransmitters
Purinergic neurotransmitters: adenosine triphosphate or ATP has some biological activity at synapses in CNS.
ATP can be co-released with small molecule neurotransmitters.
It is metabolised in extracellular space into adenosine.
Adenosine has its own biological activity: binds to various receptors, for example in hypothalamus (adenosine is important trigger that leads to drowsiness).
Caffeinated beverages block adenosine receptors.

22. Unconventional neurotransmitters
Endocannabinoids: tetrahydrocannabinol (THC), hydrophobic molecules.
Endocannabinoids bind to CB1 receptor which is present in high concentrations in structures associated with the brain´s reward system.
CB1 is present throughout the cerebral cortex, in the cerebellum and in the basal ganglia.

23. Unconventional neurotransmitters
Endocannabinoids have role in modulating plasticity, especially plasticity at inhibitory synapses.

24. Nitric oxide
It is a gas which is produced from the metabolism of the amino acid arginine.
Arginine is processed by nitric oxide synthase.
Nitric oxide has ability to diffuse freely from postsynaptic cell to a presynaptic cell: retrograde messenger?
NO is vasodilatator.

25. Synthesis
Small molecule transmitters are synthesized in the presynaptic terminal.
Peptide neurotransmitters are synthesized in the cell body.

26. Vesicles
Small molecule transmitters are packaged into vesicles that are concentrated along the active zones at the presynaptic membrane.
Peptide transmitters are found in vesicles that are diffusing around the presynaptic terminal further away from that active zone.
Peptide transmitters are released only when there is intensive depolarisation of the presynaptic terminal (large calcium influx).

27. Literature
neuroscience/lecture: Leonard E. White, PhD, Duke University
Neuroscientificallychallenged.com
Knowingneurons.com

28. Literature
News.mit.edu
Counselheal.com
Bethopedia.com