Summery Hormones and the nervous
system.
CNS= Central nervous system.
1. Chemical Neuroanatomy of the Brain
Read:
Bear, Connors & Paradiso, Neuroscience 4th Edition, Study material:
- Chapter 5 p110-132: Synaptic transmission, Principles of chemical synaptic transmission.
- Chapter 6 p144-163: Neurotransmitter systems. Study the different techniques that can be used to
study neurotransmitter systems and how these systems can be manipulated with drugs.
- Use the Allen Brain Atlas to assess the localization of glutamatergic and cholinergic receptors in
man and mouse and see if this matched which what is written in the book.
All of the above - including the assignments - is study material for the day-test and exam. Also make sure to
review/re-do the mouse ABA assignment from the course “Introduction to the Neurosciences”.
The special topic is used for illustration purposes only and the contents will not be part of the day-test or
exam.
To review and refresh:
- Chapter 7 The structure of the nervous system p180-184, 188-191, 205-214, 231-240. Review the
different mammalian brain structures and their functions. Note differences and overlap between
humans and rodents.
- Chapter 5 Synaptic transmission, Principles of chemical synaptic transmission p110-132 Review the
difference between electrical and chemical transmission.
- Review what effect drugs can have on the chemical neuroanatomy with the Mouse Party.
Objectives:
1. The student can describe the different scales and ways of communications within the brain.
2. The student can define what neurotransmitters are and describe and how they function.
3. The student can explain how neurotransmitters can be investigated in vivo and in vitro and
describe advantages and disadvantages of each method.
4. 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.
Summery:
Extra:
it would be useful to know where these NTMs are made in the brain, so that we can link function to
localization, this is chemical neuroanatomy. there is also a huge receptor diversity.
Dopamine (like other neurotransmitters) has no gene encoding for it but is formed by enzymes.
Stress can inhibit oxytocin (=hormone neuropeptide).
EPSP (Excitatory postsynaptic potential) and ISPS (Inhibitory postsynaptic potential)> blz 126 Bear
ESPS= is a postsynaptic potential that makes the postsynaptic neuron more likely to fire an action potential
(Wikipedia)
,“name of neurotransmitter”-ergic = if it pertains to (=betrekking op) or affects the specific
neurotransmitter. For example: GABA, a synapse is GABAergic if it uses GABA as its neurotransmitter, and a
GABAergic neuron produces GABA. A substance is GABAergic if it produces its effects via interactions with
the GABA system, such as by stimulating or blocking neurotransmission. All the molecular machinery
associated with GABA is collectively called the GABAergic system (blz 145 Bear).
Student questions, review lesson:
• Beta blockers block the anxiety caused by neuroadrenalin.
• Antidepressant is based on serotonin
• Substantia nigra makes dopamine.
• Negative feedback need receptors, thus you can also see in the co-expression list if the area also
expresses an neurtotansmitter negative feedback receptor (some receptors are pre- and
postsynaptic)
• Stress can inhibit oxytocin.
Day test:
How to show the noradrenalin production best in Allen’s brain atlas: look for TH, DDB and DBH (and an 3th
that makes dopamine into the noradrenalin). Don’t use PNMT because that makes Epinephrine from
noradrenalin (fig 6.13, blz 157 Bear).
Ralph nuclei and hippocampus are stained for a mRNA of a substance in the serotonin pathway. Which
one?.It’s a pre-and postsynaptic receptor, but it could also have been a transporter. It can’t be an serotonin
making enzyme since the hippocampus doesn’t make serotonin (thus then one only the raphe nuclei
should light up).
There is an protein with two RNA splice variants, is Allan’s brain atlas useful when you want to localise the
place of the protein? Splicing only alters a small part of the molecule, thus if you only want to distinguish
then that would be hard since the probes wouldn’t be really able to distinguish them. But if there are
specific probes, then you can distinguish between the two variants.
What extra approaches can you use?
Immunocytochemistry with specific antibodies for specific splice variants or Fluorescence microscopy
(protein> need specific antibody, but for receptor> use an ligand). RNA-sequencing, western blot, etc.
The student can describe the different scales and ways of communications within the brain
Scales?: Functional connectivity> structural connectivity> synaptic communication.
development of physical connectivity:
• grey matter reduces; is pruned
• white matter increases; myelin increases
Both processes change the look of the MRI images
Mechanical energy into neuronal signal: specialised ion channel on the end of the sensory nerve allow
positive charge to enter the axon> depolarisation> depolarisation reaches threshold> action potentials are
generated> signals are send to the next destination.
Neurotransmitter (NTM)(blz 122-130 Bear): neurotransmitter release by the presynaptic neuron activates
due to an action protentional> depolarisation causes the voltage-gated calcium channels to open (in active
zone)> influx of Ca2+(the signal to release neurotransmitter)> neurotransmitters are exocytosed by the
,vesicles (synaptic vesicles: fusion of vesicle membrane and active zone membrane, vesicle is recycled by
endocytosis) (Secretory granules: not at active zones and need a high frequency trains of action potentials)>
neurotransmitters in the synaptic cleft> receptors (see next learning point)> reaction> recovery and
degradation of neurotransmitters in synaptic cleft (how+ desensitization, see blz 130)> end of signal.
The neurotransmitter MUST be cleared from the synaptic cleft to allow another round of synaptic
transmission.
Synaptic transmission= the process of information transfer at the synapse. Types of synapses:
• Electrical synapse (blz 111 Bear)= allow direct transfer of ionic current from cell to the next cell.
Occur at Gab junctions (3nm wide) which are interconnections between cells that allow equal ionic
current in both ways (mostly) and are thus bidirectional (blz 112, fig 5.1 Bear). Gab junction
contains a connexon on each side of the cell> two connexons (1/cell) form a gab junction channel
that can transfer ions directly from the cytoplasm. Gab junction between neurons function as
electrical synapses. Fast and nearly fail-safe. Common in every part of mammal CNS. Variable
functions in different brain sites, often used when the activity of neuron neighbours needs to be
synchronised.
Action protentional presynaptic neuron> small ionic current trough the gab junction channel>
postsynaptic potential (PSP) in the postsynaptic neuron (but bidirectional> also PSP in presynaptic
neuron) > one/multiple PSPs> action protentional postsynaptic neuron> etc.
• Chemical synapse (blz 113 Bear)= transfer of signal via neurotransmitters (blz 115, fig 5.4 Bear).
Most are unidirectional. Most synaptic transfer in the mature human nervous system is chemical.
synapses are separated by an synaptic cleft (20-50nm) filled with matrix (fibrous). The presynaptic
element (presynaptic side of the synapse) contains synaptic vesicles (with neurotransmitters) and
secretory granules (with soluble proteins(neurotransmitters)) and releases them at the active
zones(=protein accumulation on/in the intracellular side of the membrane (tethered, anchored of
embedded)> released neurotransmitters bind the receptors in the postsynaptic density (=protein
accumulation beneath the postsynaptic membrane)> an intracellular signal is generated. The active
zone and the postsynaptic density are membrane differentiations. Types:
o CNS chemical synapses: subtypes based on postsynaptic part of the neuron (blz 115, Bear)
or on appearance of their presynaptic and postsynaptic membrane differentiations (similar
thickness or not)(blz 117, Bear). Synapse sizes and shapes vary.
o Neuromuscular junction= Chemical synapse between motor neuron and skeletal muscle.
One type of the synaptic junctions outside the CNS (pheripheral nervous system).
Neuromuscular junction fast and reliable, many of the CNS structural features. Among the
largest. Motor endplate= the postsynaptic membrane.
The student can define what neurotransmitters are and describe and how they function .
Principles of chemical synaptic transmission (blz 119- 132 Bear):
There must be a mechanism:
• For synthesising and packaging the neurotransmitter.
• That causes the synaptic vesicles to spill their contents into the synaptic cleft (after action
potential).
• For producing an biochemical or electrical response to the neurotransmitter.
• That removes the neurotransmitter from the synaptic cleft.
And all in milliseconds.
Neurotransmitter(NTM)= an substance that conveys signal. 3 chemical categories: amino acids, amines and
peptides (blz 121, table 5.1 Bear).
, Different neurotransmitters are synthesised in different ways, released under different conditions and by
different neurons. Speed differs, amino acids mostly fastest (last 10-100msec), peptide slowest (needs
>50msec). Neurotransmitters are synthesised from various metabolic precursors (GABA and amines) or
synthesised in rough ER (peptides) and stored. Fast neurotransmitters are stored and released upon Ca2+
dependent exocytosis
Neurotransmitters: fast/slow, stimulating/inhibiting, cellular communication (growth, proliferation,
neuronal signalling, and more), different signalling types (ion channels receptors, or G-protein)
Dale’s principle= a neuron releases one type of neurotransmitter. Exception are many peptide containing
neurons: release an amino acid or amine and peptides. Co-transmitters: when two neurotransmitters are
released from one neuron (often GABA and glutamate).
Neurotransmitter function Search in Allain’s brain atlas
Gamma-aminobutyric Main inhibitory transmitter (in mature brain, in immature brain> Enzyme:
acid (GABA) causes depolarisation, see subject 2). -glutamic acid decarboxylase
GABAergic Only in the brain, not used as building protein. (GAD)
Receptor:
Produced by: Lot of
-GABAA
neurons in the brain
-GABAB
Received by:
Made from glutamate. -GABAC
Blz 159 Bear
Glutamate (Glu) Also building block protein (thus not only made by neurons). Main Enzyme:
Amino acids
Glutamatergic excitatory transmitter. Also kills neurons (excitotoxicity, see subject 2) -Glutaminase
Produced by: (almost) all Receptor:
cells -AMPA (GluR1-4)
-Kainate(KA1, KA2, GluR5-7)
Received by:-
Made from either glucose (citric cycle) or glutamine (Astrocytes -NMDA (NMDAR1, 2A-D)
Blz 159 Bear
(glial cells)). -mGluR1-8
Glycine (Gly) Also building block protein (thus not only made by neurons). Inhibits Enzyme:
Glycinergic most that GABA doesn’t. Receptor:
Outside the brain.
Produced by: (almost) all
cells
Received by:-
Blz 159 Bear
Made from glucose.
Acetylcholine (ACh) Found at the neuromuscular junctions. Also in cells that contribute to Enzyme:
cholinergic circuits in PNS and CNS. -Choline acetyltransferase
(ChAT)
Produced by: all Nicotine: does bind skeletal muscle ACh receptors, but no heart ACh -Acetylcholinesterase (AChE)
motor neurons in the receptors. Receptor:
Amines
-Nicotinic ACh receptor:
CNS, also in cells of
in skeletal muscle,
ChAT makes ACh (how> see Bear) in cytosol and ACh transporter brings it into
the PNS. the vessel. For whole circuit> see fig 6.10, Bear. bound by agonist nicotine.
Received by:- AChE degraded ACh into choline and acetic acid. -Muscarinic ACh receptor:
Blz 154 Bear in heart, bound by agonis
Made from acetyl CoA (from mitochondria) and choline muscarine.
(fat metabolism).
Serotonin (5-HT) play an important role in the brain systems that regulate mood, Enzyme:
Serotonergic emotional behaviour, and sleep. -Tryptophan hydroxylase (2)
