Summary Introduction to Neuroscience

Summary Introduction to Neuroscience


Lecture 1 – Neuropharmacology
Basic information of synaptic transmission:
 Synaptic transmission:
- 1. Neurotransmitter molecules are synthesized and packaged in vesicles
- 2. An action potential arrives at the presynaptic terminal
- 3. Voltage-gated Ca2+ channels open. Ca2+ enters.
- 4. A rise in Ca2+ triggers fusion of synaptic vesicles with the presynaptic membrane
- 5. Transmitter molecules diffuse across the synaptic cleft and bind to specific
receptors on the postsynaptic cell
- 6. Bound receptors activate the postsynaptic cell
- 7. A neurotransmitter breaks down, is taken up by the presynaptic terminal or other
cells, or diffuses away from the synapse
 Neuron always overshoots and takes back, in order to see the end of a signal
 Cannabinoids: We have cannabis-like neurotransmitters (opioids: endorphins) that bind
to the same receptors as cannabis itself
 Neurons’ trick:
- The neuron has a way to excite membrane
- Neurotransmitters cause small changes in postsynaptic membrane potential (PSP)
- Size of change depends on type of transmitter
 Excitatory Post Synaptic Potential (EPSP)
 Glutamate, Glycine, Acetylcholine, (Nor)epinephrine, Serotonin
 Inhibitory Post Synaptic Potential (IPSP)
 Gamma-aminobutyric acid, Dopamine
- Textbook neuron: Can stop any decision of the dendrite/cell body by blocking its
axon terminals
- Signaling molecules can affect neuron activity at different areas
 Dendrites, Soma and Axon
- Receptors:
 One synapse has many receptors (in cell membrane)
 Neurotransmitter binds to receptor
 Ion channels or channel blocker (beta blocker)
 Neurotransmitters:
- Serotonin: Nuclei raphes (only place where serotonin is made)
- Diffuse neuromodulatory system: One compound can affect whole brain
- Transmitter binds > receptor becomes active
 Channel opens up OR it blocks the channel
- Neurotransmitters have different effects on different receptors (genes/(sub)types)
 (Avoiding) contradiction
 There are differences in sensitivity of receptors
- Global vs. local synthesis:
1. Dopamine: 5 receptor genes
2. GABA: 3 types + many subtypes
 Most prominent inhibitory transmitter
3. Serotonin: 15 receptor genes

, 4. Glutamate: 4 types + subtypes
 Most prominent excitatory transmitter
 Impossible to say where GABA and glutamate are for, as they are
involved in literally anything
5. Acetylcholine: 2 types + many subtypes
- Receptor type influences the response of the receptor
 E.g. serotonin can make something more active but could also make something
less active
 E.g. adrenalin has 2 types of receptors: Some vasoconstrict (higher blood-
pressure = more energy for muscles) and some dilate (around the face to lose heat)
 Neuropeptides:
- E.g. Vasopressin, Oxytocin, Substance P, Endorphin etc.
- Linked to specific behavioral effects
- Almost direct response

General neuropharmacology:
 Knowledge of neuropharmacology:
- How do neurotransmitters act at receptors (and what of other neuroactive
molecules?)
- How can we use this with drugs we choose to deliver to people and other animals?
 Pharmacology = dynamics & kinetics
- Dynamics: What does a drug do to the body?
 Consequences of receptor activation
- Kinetics: What does the body do to a drug?
 Absorption, distribution, elimination
 Receptors:
- Human cellular targets
 Proteins: Receptors, enzymes, ion channels
- Four receptor classes:
1. Ion channels (milliseconds): Direct effect on firing
 Change the charge of a neuron (positive ions go in; negative go out)
which causes it to fire
 Ligand-gated ion channels
 Glutamate, GABA, Acetylcholine, Serotonin
2. G-protein coupled receptors (seconds): “Domino effect” with certain
outcome that gets kicked in place (open and close)
 They sit in a membrane (stick out of a cell to probe the external
environment; “antenna”) and they kick proteins towards places
 Many transmitters (and peptides)
 Effect mechanism = G-protein
 Stimulate or inhibit (opposite physiological effects)
3. Receptor Tyrosine Kinases (minutes)
 Also stick out of the membrane of the cell; These are often related
to growth (insulin); Important for development of the NS
 Growth factors: Nerve Growth Factor & BDNF
 Cognition (learning/memory)
4. Nuclear receptor (hours)

,  They are behind the membrane, so it does not probe at all; The
hormone has to enter the cell by itself; They are relatively rare
 Effector mechanism = mRNA synthesis
 Long-term effects (changes cell and response of cell to other stimuli)
- Targets other than actual (signaling) receptors:
 Enzymes (e.g. aspirine/paracetamol)
 Pumps (e.g. antidepressant targets)
 DNA (e.g. chemotherapy)
 Structural proteins (e.g. antibiotics > bind to bacterial cell wall)
 Early “pharmaca”:
- Exogenous:
 Natural products: Natural resources used medicinally
 Phytotherapy (“forever”) & Purified (opium; 1805)
 Synthetic drugs: Reproducing natural resources (e.g. aspirin from willow
bark)
 Aspirin & Penicillin
- Endogenous:
 Neurotransmitters (networks > local effects)
 Hormones from other human/mammal products (blood > global effects)
 Testis extract (1848) & Neurotransmitters (Vagusstoff (1921))
 Drug action: From molecule to “population”:
- Agonists & antagonists:
 Agonists: Activate receptors (not necessarily the tissue!)
 Stimulate the nerve to the heart (n. vagus) > heart rate gets lower >
acetylcholine is released > binds to its receptor (GPCR) > delays contraction
 Add acetylcholine-R agonist > heart beats slower
 Like the endogenous transmitter; it activates the receptor
 Then add acetylcholine-R antagonist > heart beats faster
 Blocks the agonist effect by binding to the same receptors (= channel
blocker)
 Agonists have higher affinity > harder for antagonist to have an effect

, Lecture 2 – Introduction & History
History
(Not exam material)



Methodologies
 Hans Berger (1873-1941): Electroencephalogram (EEG)
 Rontgen (1845-1923)
- Skull X-ray
 Ventriculography
 Angiography
 Computed (Axial) Tomography
- Hounsfield (1959): EMIDEC 1100 > first large all transistor computer
- Cormack (1963): Mathematical equations for axial tomography
- Hounsfield (1971): First CAT scanner (head only)
 Magnetic Resonance Imaging (MRI) in medicine
- Edward Purcell + Paul Lauterbur + Raymond Damadian + Peter Mansfield
- Series of inventions starting in 40’s
- Culminating in medical MRI in 70’s
- Lawrence Minkoff (1970): First human MRI (heart + ribcage)
- MRI Scanner:
 Harmless
 Many possibilities: Morphology + Functional imaging + Arterial spin labelling
+ Spectroscopy + Diffusion Tensor Imaging (movement of water) + Tract
tracing + Blood flow
- Resolution still improving!
- Saturation imaging: Active brain tissue uses oxygen
- fMRI (functional): Medicine + Moods + Disorders
- Many questions regarding cognitive functioning of our brain will be resolved in near
future using (f)MRI!



LUMC
 Leiden Institute for Brain and Cognition: Interdisciplinary + State of the art
 Gorter Institute: 7T MRI scanner + Highest field in Netherlands