Neurotransmitters Domina Petric, MD

Neurotransmitters classes small molecule neurotransmitters peptide neurotransmitters

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

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.

Small molecule neurotransmitters aminoacids: glutamate aspartate GABA glycine

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

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.

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.

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.

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

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

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).

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.

Striatum Neuroscientificallychallenged.com

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

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.

www.mhhe.com Counselheal.com Locus coeruleus

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

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.

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

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.

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.

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

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.

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

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).

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

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