This document summarizes neurotransmitters and their functions in the nervous system. It describes two main classes of neurotransmitters - small molecule neurotransmitters like glutamate, GABA, and acetylcholine and peptide neurotransmitters. Small molecules can interact with both ionotropic and metabotropic receptors, while peptides only interact with metabotropic receptors. The document also discusses key neurotransmitters like dopamine, norepinephrine, serotonin, and nitric oxide as well as their roles and where they are produced in the brain.

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

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. Neuroscientificallychallenged.com
Striatum

15. Neuroscientificallychallenged.com
Ventral tegmental area
Knowingneurons.com
news.mit.edu Ventromedial
prefrontal
cortex

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
www.mhhe.com

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
• https://www.coursera.org/learn/medical-
neuroscience/lecture: Leonard E. White, PhD,
Duke University
• Neuroscientificallychallenged.com
• Knowingneurons.com

28. Literature
•News.mit.edu
•Counselheal.com
•www.mhhe.com
•Bethopedia.com