1.1-2.1 Intro Flashcards
What do we know about the NS? : Descartes (3)
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That we are thinking
Descartes ““I think, therefore I am” (cogito ergo sum
Thought is a private experience and we are aware that we exist.
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What ELSE do we know about the NS? (3) 1.1
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- We are embedded actors in an ““externum”” (environment)
- Capacity for action
- Attributes about ourselves (internal state/how we are feeling
All of these are products of operation of the NS
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Ancient Egyptians view of NS? (3)
Cardio-centric view
- Health of body and mind related to flow of fluid (Like viability of land - River Nile).
- Problems result from too little/too much flow.
- Heart = Mind’s Centre = Centre of flow
Ancient Greece: Hippocrates view of NS?
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450BC Hippocrates: Brain-centric view
"”from nothing else but the brain comes joy, delights, laughter and sports, and sorrows, griefs despondency and lamentations””
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Aristotle’s View of NS? (1)
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300BC. Cardio-centric view, despite growing accepting of brain as seat of the mind
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Roman Empire? (3) - 200AD Galen and Others
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200AD Galen: Both cardio-centric and brain-centric. Tripartite view (Brain, Liver, heart) Accepted the classical explanation of humours of the body
- Brain: Intellect
- Liver: Animalistic/Instinctive functions
- Heart: Passion; ““Growing and Living”
Synthesis of a corpus of anatomy found a ‘3rd system’ (Nervous system), supplying tissue and connecting brain and spinal cord. Therefore, while the renaissance reinstated the importance of detailed observation and question, primacy of humours as mechanistic explanation prevailed
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Reasons for adopting a cardio-centric view of the mind? (6)
- Heart moves, brain sits there
- Simple animals can move and react without brain
- Warmth (= life) emanates from body’s core (heart)
- All known civilisations held heart to be centre of conscious being
- Language contains references to heart as locus of mental experience (e.g., learning by heart)
- Observations that more sophisticated animals have bigger, more convoluted brain can be explained that more heat is generated from heart so more cooling of blood is needed
In NS history, who appreciated the role of the brain (And caveat)
What did others think?
Hippocrates in Ancient Greece then Galan in Ancient Rome appreciated the role of brain but saw its function in terms of 4 humours of the body
Others early views, From ancient Egypt to Aristotle to enlightmenet, ascribed functions to heart
Late Renaissance/Early Modern? (2)
1660AD Descartes
- Mechanical machine: Mechanism of fluid, tubes, and chambers gland
- Inspired by hydraulics
- However, the mind was immaterial, not a mechanical device (Pineal gland). Pineal gland integrates outcomes of physical structures
- Pineal gland controls fluids
Modern Neuroscience view of NS? (2)
What is the implication?
AD 1861 Paul Broca
- Right hemiplegic patient (Damage to right temporal lobe) was unable to produce speech, but can understand language
- Demonstrated localisation of function (Modularity)
Rise of Neurology allowed structured analysis of brain disease
Functions of the NS? (3) 1.3-1.5
- 3 Function of NS 1 - Capacity for Action
- 4 Function of NS 2 - Egocentric External Universe
- 5 Function of NS 3? - Monitor and Control Bodily Functions
1.3 Function of NS 1 - Capacity for Action
Relationship between Genes and NS
Not all complex organisms have a nervous system. An animals’ genome does not inform much about the NS
Arabidopsis thaliana
Complex organism (27,000 genes) but no nervous system. Does not move
Corynactis californica
A “nervous system” comprising a network of nerve cells. Able to move a bit
1..4 Function of NS 2 - Egocentric External Universe
Properties of external/ real world are conscious experiences generated by actions of the nervous system
What do we still not know about NS? (1)
Despite the increasing recognition of the brain as the origin of our mental existence, an understanding of the mind as a function of the brain, i.e., how the mind is generated by the brain, has not emerged. (How the brain produces consciousness)
What are the 3 repugnant ideas of how the NS worked in 1700s? (3)
- Sprits running through hollow nerve fibres, conveying impressions to the brain and activating muscles Descartes’ fluid mechanical model)
- Mini explosions, caused by fermentation from mixing of fluid droplets from the nerve ends and blood, activating muscles (Chemistry): Nerves release some chemical which causes a chemical explosion which activates the next nerve (or muscle)
- Vibrations, light of different energies transferred vibrations to nerves, conveying sensations to the brain (Physics): Nerves vibrate and signal is transmitted from brain to muscles
Evidence against the 3 repugnant ideas of how the NS worked in 1700s? (4)
- Limbs do not increase volume when muscles are activated (Displacement of water does not go up because of increased bulk of muscles, suggesting there is no transfer of fluid)
- Nerves cut underwater did not result in bubbling (No pressure in the system)
- Ligation (Cutting) of nerves didn’t cause accumulation of fluid (No fluid coming out)
- Fluid could not move fast enough to explain NS speed
17th Century: Huge interest in Electricity: Background as to how this was sparked
Relationship between electricity and biology is mainly conferred from electric animals like electric eels - Could see nerves running into those modified muscles that conduct electricity; thus, it was conveying a signal that release stored animal electricity
17th Century and Electricity
Evidences that nerves were related to electricity (2)? Galvani and Aldini
(1780)
- Galvani discovered that electrical stimuli where much more effective in contracting a muscle if they are applied to the muscle’s nerve rather than directly to the muscle, and postulated that nerves contain or conduct “animal electricity”
- Aldini managed to activate facial muscles by stimulating the brain of severed heads (But failed to produce any results by stimulating spinal cord)
Limitations of evidences in the 1700s: Resolution (1) and When do we know about electricity? (1)
Lacked cellular resolution
Only in 1850s, with the detection of tiny currents produced by nerves, could we confirm that nerve signals via. electrical impulses.
The potential difference during electrical stimulation? (Image)
Define Resting; Passive Response; AP
Resting: -65mV
Passive Response: Hyperpolarisation/Depolarisation (Not threshold)
AP: All or Nothing (Intensity reflected in frequency, not amplitude)
How is the resting membrane potential established
Potassium dominates the ionic flux at rest.
At electrochemical equilibrium, there is an exact balance between two opposing forces:
- Concentration gradient that causes K+ to move from A to B, taking along the positive charges
- Opposing electrical gradient that increasingly tends to stop K+ from moving across the membrane (K+ repels one another)
Properties of Ion Transporters:
- What kind of proteins are they?
- Energy and Concentration Gradient
- Importance
- Usually multimeric proteins in plasma membrane of the neuron
- Actively move ions against concentration gradient (Uses ATP). Called electrogenic pump
- Important for thousands of AP and maintaining the potential difference (e.g., if the difference starts to decline) does not have a role in the setting up the initial potential difference.
How do we know ion transporters are only important in maintaining MP difference? Experiment that inhibits ion transporters
- When ouabain, an ATPase inhibitor is applied, stimulating still gave muscle twitch. However, after a number of rapid stimulations, there was a decline in the twitch response
- The decline was because ion transporters were not able to maintain the -65 RMP; RMP slowly increased, and the gap between the peak and the bottom decreased
- This suggests we only need ATPase to maintain the RMP, and the cell can actually passively move to RMP without their intervention
What are ion channels? (3)
- Concentration gradient (And Energy)
- Properties (Permeability and Direction)
- Importance
- Allows ions to diffuse down concentration gradient (No ATP)
- Some:
- Selective permeability to certain ions such as only allowing Na+ or K+
- Non-selective (e.g., non-selective cation channels)
- Rectifying: Only allows one direction of transport
- This selective permeability is the key to how resting membrane potential sets up (initial setup)
What happens if a channel is non-selective? (1)
If channel is non-selective, both positive and negative ion will diffuse, leading to net zero movements.
What is the key to generating and modulating action potentials? What does myelination do?
- Electrical impulse travels along the neuron as a result of voltage-gated Na+ and K+ ion channels opening and activating adjacent voltage-gated Na+ and K+ ion channels
- Myelination increases conduction velocity, where the electrical impulse jumps from node to node
End of 19th Century: What was the main contribution of microscopy
By the end of the 19th Century, Neuron doctrine had prevailed: Neurons were made of discrete cells and not a reticular network (vs Reticular theory)
Unanswered question before Microscopy
We know that nerve tissues are excitable and generate electrical impulses; however, the nature of the nerve cells themselves and their interrelationship was unclear: Are nerves a continuous connection or discrete elements signalling to one another?
Researchers involved in microscopy/cell theory: Schwann, Leeuwenhoeks, and Robert Hooke
Proponents of Cell Theory, though it was thought to inapplicable to the NS
Who was the first to suggest that NS, like other tissues, were composed of discrete cells
Purkinje
Golgi (1840s)
Silver staining of single nerve cells in tissue showed neurons were cells in the nervous system.
Cajal (End of 19th Century) (2)
Further refined silver staining technique
Discovered growth cones and dynamic morphology of growing neurons - Raising the question of whether the same plasticity occurred in adult brains
Unanswered question despite Microscopy (1)
Despite higher resolution microscopy, it is still unclear how signals, travelling along neural process as electrical events, pass from one neuron to the next
This is one of the reasons why people argued that NS wasn’t cellular
What is the Cytoarchitecture Map
Showed different brain regions to have different neuronal organizations (i.e., Broadmann areas)
Studying synaptic transmission: Where did most evidence come from and why?
Much evidence came from studies of how nerves affect peripheral targets; how motor nerves signalled to skeletal muscle and how the sympathetic and parasympathetic nerves affected target organs in the body
This is because looking at synapses out in the periphery is relatively easier to examine compared to the brain
Sherrington’s View (2)
- Supported the Neuron doctrine even before Cajal’s evidence
- Proposed a junction between neurons, synapse. This synapse was a purely hypothetical entity as electron microscopes were not invented yet
Sherrington’s Observations (Which led to his view)? (3)
- Degeneration of the NS always resulted in a discrete, demarcated pattern of loss, rather than diffuse loss (neuronal death only caused death of a single neuron, not the entire network)
- Reflex responses were slower than expected by the speed of nerve conduction (there was a delay somewhere)
- Reflex conduction unidirectional
How are transistors related to the CNS? (3)
- Transistors, acting as switches, can perform Boolean (true/false) logic
- Synapses have the capacity to perform logical computation
- Synapse = Transistors
- e.g., If A comes down, pass along. If A + B comes down, do not pass along
- Hence, synapses act as points of control over information transmission.
First evidence of chemical transmission: George Oliver and Hendry Dale (1)
George Oliver and Hendry Dale found a number of naturally occurring substances (from plants and funguses) that mimic effects of nerve stimulation on peripheral structures
Second evidence of chemical transmission: Unnamed (1)
Applying crushed up adrenal glands to blood vessels caused vasoconstriction. This suggests there’s a substance made by the body in the adrenal gland that is a potent vasoconstrictor.
Third evidence of chemical transmission: Ottoe Leowi
Ottoe Leowi mimiked the effects of sympathetic and parasympathetic nerve stimulation by applying the fluid collected during the stimulation to another non-stimulated heart
Both direct nervous stimulation and indirect chemical stimulation caused slowing of HR
What are the criteria that define a neurotransmitter? (3)
Be present (in form of vesicles): NT present
Released under the right circumstances (VGCa2+ opens): NT released
Activate NT receptors on postsynaptic membrane
Chemical Synapses: Variety; Speed; Energy
Variety (1)
- Over 100 NTs; Huge variety of receptors
Energy Required (1)
- Energy-dependent processes (synthesis release, reuptake)
Speed (1)
- Slow, due to complex energy-dependent release machinery, diffusion, and post synaptic receptor activation.
Electrical Synapses
Direction (2)
Energy Required (1)
Speed (1)
Utility (1)
Direction (2)
- Typically bidirectional (effects depend on recent or concurrent activity)
- Always excitatory
Energy Required (1)
- Passive transmission, no complex energy-dependent release machinery
Speed (1)
- Fast, no long latency due to complex energy-dependent release machinery, diffusion, and post-synaptic receptor activation (Might be important for survival)
Utility (1)
- Good for synchronisation of neuronal groups
What can be inferred about post-synaptic effect of a particular NT based on its chemical nature and structure? (1)
Nothing. Post-synaptic effect (excitatory/inhibitory) depends on receptors, not NTs.
What are the four kinds of receptors? (4)
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Channel-linked/Ion channels (Can tell effects based on what ion goes in)
Enzyme-linked receptors
G-protein-coupled receptor (2nd messenger)
Intracellular receptor
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Important feature of chemical synapses: Relating to neural plasticity?
Efficacy of chemical synapses can be ______
Efficacy can be modulated in proportion to how active they are and the precise timing of that activation, and this can be related to other synaptic inputs to the same neurons.
This capacity for changing influence in relation to activity is a form of neural plasticity
The experiment of LTP?
Stimulate either CA3 and CA1 and investigated changes
Pathway 1: Baseline EPSP measured > 100 stimulation > increased EPSP for subsequent single electrical stimulus (twice as big after tetanus)
Pathway 2: Baseline EPSP measured > no increase in EPSP for subsequent single electrical stimulus
Types of plasticity? (2 + 2)
Specific
- Continuous stimulation of 1 synapse strengthens that synaptic connection
- No other synaptic connections on that post-synaptic neuron are strengthened
Associative
- Continuous stimulation of 1 synapse strengthens that synaptic connection
- Other synaptic connections on that post-synaptic neuron are also strengthened
Mechanisms of LTP: Is it pre or post-synaptic?
Compare resting potential vs depolarisation
Mechanism of LTP is Post-Synaptic
At resting potential (3)
- Glutamate released and binds to receptors
- AMPA receptors open (Na+ enters)
- NMDA receptor do not open as Mg2+ blocks
At postsynaptic depolarisation (3)
- Glutamate released and binds to receptors
- AMPA receptors open (Na+ enters)
- NMDA receptor opens as Mg2+ is expelled, allowing Ca2+ influx
What are the effects of Ca2+ entering the cell?
Effects of Ca2+ is large, such as:
- Increase the number of AMPA receptors, making the cell more excitable (Key)
- Alter gene expression, changing the structure of the synapse
Role of protein synthesis in LTP?
In the LTP experiment in the presence of a protein synthesis inhibitor, we get a much reduced EPSP enhancement (so production of new protein is important in LTP)
Before high resolution methods, how do we deduce neural disorders? (2)
- Correlation between neural structure and function was deduced from clinical examinations (Examination of spinal and cranial nerve function is still part of neurological examination)
- Neurological diagnoses can localise sites of NS dysfunction by examining site-specific functions
Comparing resolutions (Eyes, Light Microscope, Electron Microscope)
- Eye
- Light Microscope (Thickness of hair, Cell, Bacterium)
- Electron Microscope (Cell, Bacterium, Virus, Macromolecule, Atom)
Light Microscope: What dictates resolution? (1)
Wavelength of visible light (250nm)
Light Microscope: What limits the resolution? (3)
Diffraction of Light.
- Light acts as a wave; when it meets refractory boundary, it interferes with itself, forming diffraction/interference patterns.
- Single point of light coming through the lens spreads to create a point-spread function (PSF) or airy disc
- In an image, each point has a PSF, limiting resolution
Electron microscope: What dictates resolution? (1)
Wavelength of the electron beam
How do electron microscopes work? (1)
How does it relate to the PSF (1)
It controls activation and deactivation of fluorescent molecules
Electron microscope looks in the PSF peak (High resolution point), and combines millions of them to build an image
Examples of electron microscopes?
Stimulated emission depletion (STED)
Stochastic optical reconstruction (STORM)
What is Stimulated emission depletion (STED)
Use a laser to precisely deactivate the outmost portion of the diffraction disc (airy disc) while leaving the centre focal spot active to emit fluorescence, thereby narrowing the disc’s point spread function
Stochastic optical reconstruction (STORM)
Single-molecule imaging: Random switching of fluorescence of individual molecules allows single molecules to be imaged. Repeat for many cycles to construct image from millions of locations.
Advantage of light microscope over electron microscope
Ability to use fluorescence to glow different colour, despite the narrow visible spectrum, whereas electron microscopes can only look at where the heavy metal stains have been
Advantages of Patch Clamp Electrodes? (2)
- Resolution
- What does it measure
- High spatial and temporal resolution
- Allows us to measure voltage inside the cell, and activity of a specific ion channel in isolation (Single channel)
Overview (2) EEG
Surface electrodes to measure the electrical activity of the brain
Neurons in the cerebral cortex are aligned (apical dendrites in the same orientation) and behave together, firing synchronously, allowing us to record their activity from the scalp
EEG:
Resolutions and Utility
Pros (2)
High temporal resolution
Useful for measuring brain activity in different states of consciousness
Cons (1)
Low spatial resolution
Overview (1) MEG
Measures the normal (but very small) magnetic fields associated with brain activity
Pros and Cons MEG
Pros (1)
High temporal resolution
Cons (1)
Poor spatial resolution (Difficult to localise origin of signal)
Define Tomographic Techniques
Measure the activity or structure of a slice of the brain using non-visible electromagnetic radiation spectrum (Can be either non-damaging like RF or damaging like gamma)
What are non-damaging vs damaging EM Radiation waves
Ionizing radiations
- Gamma
- X-ray
Non-ionizing
- UV
- Visible
- IR
- Microwave
- RF
Overview (1) CAT
Beam of X-ray passes through brain and X-ray detectors compare difference in densities from different angles. Computer reconstructs an image of each slice.
Pros (1) CAT
Non-damaging (X-rays are damaging to tissue, but CAT scans use relatively small doses)
Cheap
Overview (1) PET
Injects radio-labelled compounds and detect photon emissions
Pros (1) and Cons (2) PET
Pros
- Activity-related measure based on oxygen and glucose (Does not give structural-related data like CAT scan)
Cons
- Low resolutions (spatial and temporal)
- Uses ionising radiation which are harmful in large doses (limit scans)
Overview (4) MRI
- Placed in large magnetic field where protons absorb electromagnetic energy
- After absorbing, the nuclei release this energy so that they return to their equilibrium state
- MRI signal picks up this transmission of RF energy by the nuclei as they return to their equilibrium state
- Great majority of the protons are water molecules, producing a significant signal (Hence, MRI actually measures density of water - Not so much water in white matter, more so in grey matter)
Pros (3) MRI
- Uses radio waves (not harmful)
- Gives both structural (like CT) and functional (like PET) data
- High spatial resolution
Cons (1) MRI
Poor temporal resolution
fMRI BOLD overview
Active area has more oxygen, increased blood flow, and increased signal, decreased [Hbr] (decreased deoxygenated haemoglobin).
Since properties of protons in oxygenated and deoxygenated differs, BOLD exploits signal decay of de-oxygenated blood, rather than measure blood flow.
fMRI Pros
High spatial resolution
fMRI cons (3)
Cons (3)
- Poor temporal resolution as there’s a delay for increased blood flow (autonomic response)
- Doesn’t measure neuronal activity
- Signal can be difficult to extract from noise from routine changes in blood flow
Patch Clamp, EEG &MEG, PET, fMRI
- Compare them via. spatial resolutions and temporal resolutions (General comparison)
Spatial
High: Patch Clamp, fMRI
Low: PET, EEG & MEG
Temporal
High: Patch Clamp, EEG & MEG
Low: PET, fMRI
