Summary Learning Objectives Hormones and the Nervous System
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Course
Hormones and the Nervous System (311200170Y)
Institution
Universiteit Leiden (UL)
Summary of all lectures, prescribed articles, and concepts from day tests applied to the specific learning outcomes described in the course syllabus. Supportive images are included.
Learning Outcomes Hormones and the Nervous System
Learning Outcomes Hormones and the Nervous System 1
1. Chemical neuroanatomy of the brain 2
2. Glutamate and GABA 4
3. Synaptic Strength 9
4. Autonomic Nervous System 14
5. Neuropeptides 19
6. Trophic Factors CNS 23
7. Nuclear Receptors 26
8. Brain Enhancement 29
9. Leptin and Food Intake Regulation 31
10. Big Data in Neuro-Endocrine Research 34
11. Circadian Rhythms 38
12. Dopamine: Reward and Addiction 42
13. Oxytocin and Vasopressin 47
14. Thyroid Hormone 52
15. Pharmacokinetics 60
16. Serotonin and Dopamine in Psychopathology 69
17. Fertility and Menopausal Women 74
18. Opioids and Pain 81
19. Corticosteroids and Stress 87
20. Growth Hormone 89
21. Aging 94
22. Adrenocortical Diseases 100
1
,1. Chemical neuroanatomy of the brain
The student can describe the different scales and ways of communications within the brain
● Communication within the brain occurs via signal transduction, which is mediated by synapses.
● Synapses can be either electrical or chemical.
● Electrical synapses are formed by gap junctions composed of connexins that facilitate the flow
of ions.
● These gap junctions connect the cytoplasm of two cells allowing for bi-directional passage of
ions and small molecules. As a result, when one neuron induces a postsynaptic potential (PSP)
in the next neuron, this PSP will also generate a PSP in the first neuron.
● Chemical synapses consist of a synapse and pre-and postsynaptic membrane. Dense-core
vesicles containing neurotransmitters (NT) are released from the presynaptic membrane upon
axon terminal depolarization.
● The NT binds to its receptor on the postsynaptic membrane in the region called the postsynaptic
density.
● The postsynaptic membrane can be on the dendrite, soma, dendritic spine, or another axon.
● If the postsynaptic membrane differentiation is thicker the synapse is asymmetrical and usually
results in excitatory signaling, while a similar differentiation thickness gives a symmetrical
synapse and usually results in inhibitory signaling.
The student can define what neurotransmitters are and describe and how they function
● Neurotransmitters are molecules produced in the presynaptic membrane that are released upon
stimulation and elicit a postsynaptic response.
● There are 3 classes of neurotransmitters, including 1) Amino acids such as GABA and glutamate,
2) amines such as acetylcholine and dopamine, and 3) peptides such as the hypothalamic
peptides.
● Most neurons often predominantly release one type of amine or amino acid, yet co-transmitter
release can occur.
● NTs can be directly transported from the synaptic cleft into the cytosol via a membrane
transporter that couples ion transport to NT transport.
● Then, NT are transported into vesicles via pumps that couple ions transport and NT transport via
countertransport mechanisms.
2
, ● Some lipophilic molecules, such as endocannabinoids, can signal from post-to-pre synaptic via
retrograde signaling.
● Certain small molecules such as ATP can also function as neurotransmitters.
● Cholinergic receptors function in signal transduction of the somatic and autonomic nervous
systems.
● The receptors are named because they become activated by the ligand acetylcholine. These
receptors subdivide into nicotinic and muscarinic receptors, which are named secondary to
separate activating ligands that contributed to their study. Nicotinic receptors are responsive to
the agonist nicotine, while muscarinic receptors are responsive to muscarine.
● Nicotinic and muscarinic receptors differ in function as ionotropic ligand-gated and G-protein
coupled receptors, respectively.
● Nicotinic receptors function within the central nervous system and at the neuromuscular
junction.
● While muscarinic receptors function in both the
peripheral and central nervous systems,
mediating innervation to visceral organs.
● The difference in signal transduction of the two
receptor types confers separate physiological
functions upon receptor activation.
● Furthermore, differences in receptor subtypes
create unique implications for pharmacologic
targets and pathogenesis of the disease.
The student can explain how neurotransmitters can be investigated in vivo and in vitro and describe
advantages and disadvantages of each method.
● On the macro level of the scale, both structural and functional connections in the brain can be
investigated using imaging and spectroscopy techniques.
● On the level of groups of cells, the classical tool for chemical neuroanatomy has been
immunohistochemistry (IHC): the staining of cell bodies, axons and dendrites has delineated
many individual projections from one brain area to the other.
● IHC antibodies are usually harvested from an animal by
administering the NT and harvesting the blood wit Abs against
the NT from the animal.
● On the micro level of the scale, immunocytochemistry can
anatomically localize particular molecules within a single cell
and In situ hybridization can be used to confirm if a cell
synthesized a particular protein.
● To study NT release in vitro brain slices can be kept in a
potassium-rich solution to stimulate depolarization.
● Optogenetics in which neurons are genetically modified to have
a light-sensitive protein, so that solely the modified neurons can
be activated with a light flash.
3
, ● Postsynaptic effects of a NT can be determined using microiontophoresis. Herein, a drug can be
applied to a neuron with a micropipette and Vm can be measured. The response can be
compared to synaptic stimulation.
The student can use The Allen Brain Atlas to find neurotransmitter sites of action in both the human
and mouse brain and can reason about the translation between species.
● For the Allen human brain atlas, microarray was used to assess the expression of 19.991 (!)
genes in healthy post-mortem brains from six adults. Over 500 samples per hemisphere across
cerebrum, cerebellum and brainstem were profiled
● If you want to look at the role of a certain brain part in a certain psychological or physiological
process, the activity of a NT known to be associated with that process can be distinguished in
different brain areas.
● To do so, a receptor or key synthetic enzyme gene can be looked up in the atlas to see where it is
highly expressed.
2. Glutamate and GABA
Structure and working mechanism of activation of glutamate and GABA receptors.
● Amino acids glycine and glutamate, as well as the GABA
signal via amino acidergic neurons.
● The main distinction between glutaminergic and
non-glutaminergic neurons is the transporter that loads
synaptic vesicles.
● GABA is only produced by neurons that use it as a NT.
GABA is produced from glutamate by glutamic acid
decarboxylase (GAD), therefore GAD serves as a good
marker for GABAergic neurons.
● Amino acidergic transmitters signal through both
ionotropic and metabotropic receptors, which are
ligand-gated ion channels and GPCRs, respectively.
Glutamate receptors
Ionotropic glutamate receptors
● There are 3 subtypes of glutamate-gated channels: AMPA, NMDA, and kainate channels.
● AMPA and NMDA channels mediate most of the excitatory stimulation.
4
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