Week 3-Brain Communication

Question 1

Where does the term synapse derive from?

Answer 1

-“Synapse” from Greek “synaptein”-“syn” (“together”) and “haptein” (“to clasp”)

-Introduced by Charles Sherrington (1857-1952) English neurophysiologist and histologist, Nobel Laureate 1932

-University of Liverpool 1895-1913

Question 2

How are post-synaptic potentials generated?

Answer 2

-Postsynaptic cell membrane is polarised- resting potential of approx -70mV (electrostatic pressure)

-NTs in the synaptic cleft bind to receptors on the postsynaptic membrane and open channels. This allows sodium, potassium and calcium (+), and chloride (-) ions to enter the cell changing the charge of the membrane

-Ions flow from extracellular space to intercellular space and vice versa

-This changes the degree of positive or negative charge inside the cell

Question 3

Define resting potential

Answer 3

The difference in voltage (electrical charge) across the membrane while the neuron is at rest (internally and externally aka electrostatic pressure)

Question 4

Postsynaptic Potentials Generation: What is the effect if positive ions?

Answer 4

-They increase the likelihood that a signal will be sent by the neuron by making the charge on the postsynaptic membrane more positive (e.g., -70mV to -67mV nudged towards neutrality)

-Therefore, it depolarises (nudging towards neutrality and excitation i.e., more likely to fire) the neuron in the postsynaptic cell (called excitatory postsynaptic potentials aka EPSPs)

Question 5

Postsynaptic Potentials Generation: What is the effect of negative ions?

Answer 5

-They make it less likely that a signal will be sent/fired by making the charge on the postsynaptic membrane more negative and polarised (e.g., -70mV to -72mV moving away from neutrality by using chloride ions)

-Therefore, it hyperpolarises the neuron (Called inhibitory postsynaptic potentials aka IPSPs)

Question 6

Postsynaptic Potentials Generation: How are changes in the post-synaptic potential graded?

Answer 6

-Stronger signals from communicating neurones will result in greater depolarisation (excitation) or hyperpolarisation (inhibition)

-This can be either a small or huge nudge

Question 7

Postsynaptic Potentials: What is Conduction and its 2 main characteristics?

Answer 7

-The potential conducts passively from the site of origin

1.Rapid-instantaneous movement of signal
2.Decremental-they get smaller as they travel (signals are graded)

-PSPs do not travel more than a couple of mm from their site of generation before they degrade

Question 8

Postsynaptic Potentials: How do PSNs cope with signals to determine an action potential firing?

Answer 8

-Typical postsynaptic neuron receives signals from many presynaptic neurones at the same time (thousands of synaptic connections)

-The balance between excitatory and inhibitory PSPs (aka the net effect) determines whether an action potential fires

-Integration: Combining a number of signals into one signal

-Threshold of excitation: Approx -55mV. net sum of signals reaches the ‘axon initial segment’ where then, the axon hillock (where the soma joins the axon) depolarises the membrane to this level, causing an action potential will fire

Question 9

Integration: What’s Spatial Summation?

Answer 9

Integrating multiple incoming signals over several spaces around the area of interest

Question 10

Integration: What’s Temporal summation?

Answer 10

Integrating incoming signals over time

Question 11

What causes an action potential to fire?

Answer 11

When the integration of post-synaptic potentials conducts and surpasses the Threshold of excitation at the axonal hillock

-Threshold occurs close to the axon hillock

Question 12

What are some characteristics of action potentials?

Answer 12

-The membrane potential is reversed (from negative to positively charged within our postsynaptic cell)

-Very quick (~1msec)

-Action potentials are all-or-nothing-responses

Question 13

What are the steps of an action potential generating relating to its Ionic Basis?

Answer 13

1.Resting Potential: Voltage gated ion channels are largely closed

2.Depolarisation: Na+ channels open, causing a rapid influx of Na+ into the cell (once threshold of excitation, internal cell becomes more positive)

3.Peak: Na+ channels begin to close, K+ channels open and flood as rapidly out the cell as the Na+ in

4.Repolarisation: Na+ stops entering the cell, K+ ions move out

5.Hyperpolarisation: K+ channels start to close but some K+ ions continue to move out of the cell (even more negative than the resting potential)

Question 14

Define the Refractory Period

Answer 14

The potential after the signal has been sent (like the period where you can’t flush a toilet aka generate an action potential)

Question 15

Define the Absolute Refractory Period

Answer 15

A brief period when it is impossible to generate an action potential (like the period where you can’t flush a toilet)

Question 16

Define Relative Refractory Period

Answer 16

Higher than normal levels of stimulation required to generate an action potential (extra force to flush toilet e.g.,)
(Neurones need higher levels of excitatory stimulation)

Question 17

What 2 things are the Refractory Period responsible for?

Answer 17

1.Direction of travel-ensuring signal from soma to axon
-prevents action potential from travelling backwards)

2.Rate of firing-indicating the strength of the stimulus
-A strong stimulus will allow neurones to fire quickly after absolute refractory period
-Weak stimulus will not generate an action potential quickly until relative refractory period has ended

Question 18

Action Potentials: How is the action potential conducted along the axon (aka propogation)?

Answer 18

-Travels along the axon of the neuron depolarising (more +) the axon as it goes (as previous section returning to resting potential drags the current section to the threshold excitation which becomes a chain reaction)

-In grey matter - active process (requires energy + Na+ channels opening): none-decremental

-As with AP generation, the conduction of AP along the axon occurs due to the influx of sodium

Question 19

True or False: Action Potentials travel faster when the axon is myelinated e.g., in the brains white matter

Answer 19

True! It also prevents decrementation due to its insulation (if from A to B)

Question 20

Action Potential Conduction: Define Saltatory Conduction

Answer 20

Within the myelinated of the axon the signal is conducted passively (therefore decrementally), without requiring opening of channels. This has an augmenting effect on efficiency and speed of transmission

Question 21

How are neurotransmitters categorised?

Answer 21

Categorised based on size and number of constituent parts:
1. Small
2. Large

Question 22

What are Small-molecule Neurotransmitters?

Answer 22

NTs with few components e.g., single amine components (monoamines) or short chains (amino acids e.g., glutamate and GABA)

Question 23

What are Large-molecule Neurotransmitters?

Answer 23

NTs which contain between 3-36 amino acid molecules:

-Often structurally in the form of peptides (strings of amino acids) ‘neuropeptides’.
-+100 identified, categorised into functional groups e.g., pituitary peptides, opioids or brain-gut peptides (new ones identified all the time)

-Brain-gut peptides=peptides which affect the brain and/or gut (this is what is meant by functional impact/groups)

Question 24

Define amino acids and give 2 examples

Answer 24

Amino acids are short chain molecules which come together to build peptides:

1. GABA, the brain principle inhibitory NT (PSP less likely to fire)
2. Glutamate, the most prevalent excitatory transmitter (PSP more likely to fire)

Question 25

Define Monoamines and name two types of Monoamines

Answer 25

Monoamines are made up of singular components (not short chain)

1.Catecholamines:
-Dopamine
-Norepinephrine -(noradrenaline)
-Epinephrine - (adrenaline)

2.Indolamines:
-Serotonin - 5-HT

Question 26

What is meant by modulatory neurotransmitters?

Answer 26

They can have both excitatory and inhibitory effects varying by receptor (at least 5 dopamine subtype receptors AND at least 14 serotonin receptor types BUT likely more)

-The prevalence of receptors governing various function can form patterns in the brain sometimes described as “pathways” (can travel longer distances and bring regional locations of the brain together for function) which are very visible in the brain when stained green

Question 27

What are the 4 Major Dopaminergic Pathways?

Answer 27

1. Nigrostriatral: Substantia Nigra (base of basal ganglia) –> Striatum [Motor control/ movement] (Parkinsons has dopaminergic deficiency here causes motor problems)
2. Mesolimbic: VTA –> limbic system [Reward/ Reinforcement - Addiction] VTA=ventral tegmental area
3. Mesocortical: VTA –> prefrontal cortex [Working memory and planning]
4. Tuberoinfundibular tract (hypothalamus –> pituitary) [Neuroendocrine regulation]

Question 28

What are the 2 Major Serotonergic Pathways?

Answer 28

1. Dorsal Raphe Nuclei –> Cortex, Striatum
2. Medial Raphe Nuclei –> Cortex, Hippocampus

-They travel throughout the brain through the cerebellum (serotonin is an extensive NT)

Question 29

What do the Major Serotonergic Pathways have a role in?

Answer 29

-Mood (SSRIs)

-Eating

-Sleep and dreaming

-Arousal

-Pain

-Aggression

Hard to find right combination in antidepressants due to varying side effects e.g., old tricyclic antidepressants had overeating as its most common side effect

Question 30

How are Neurotransmitters produced?

Answer 30

1. Synthesised in the cell body or terminals
2. Packaged into ‘vesicles’
3. Vesicles are released into synaptic cleft once action potential has reached the dendritic button

Release-ready pool vesicles=Docked against the inside of the pre-synaptic membrane less than 1% of the total stored in the cell (1% NTs ready to go)

Question 31

How are neurotransmitters released?

Answer 31

-Via Exocytosis

-Action potential reaches the terminal of the neuron

-Calcium ions enter the terminal

-Vesicles nearest to membrane (release ready pool) fuses with the membrane

-The vesicles then release the NTs into the synaptic cleft

-NTs will travel across the cell and bind to the postsynaptic membrane

-Large NTs are released more slowly than smaller ones

Question 32

Postsynaptic Receptor Binding: What is Fischer’s ‘Lock & Key’ Hypothesis (1890)

Answer 32

-Receptors on the postsynaptic membrane will only accept particular NTs (like a lock and key)

-Therefore NTs can only effect specific neurones

-Anything that binds to a receptor is called a ligand

-Therefore any NT is a ligand of its receptor

Question 33

Postsynaptic signal: What are receptor subtypes?

Answer 33

-Receptor subtypes vary in location and response e.g., Dopaminergic receptors - D1, D2, D3, D4, D5 (differ in their frequency with different parts of the brain)

Dopamine can bind with several of these different Dopamine receptors:
-Like a key that unlocks several different locks
-Different effect depending on the receptor/location (helps govern specific pathways and specific links to function)

-Certain areas of the brain may have more subtypes than others e.g., parts of the brain will have a lot of D1, others D5
-The same exists for the other receptor types e.g., at least 14 for serotonin

Question 34

Changing the Postsynaptic signal: What is an Ionotropic receptor?

Answer 34

-It’s a direct method

-Associated with Ligand-gated ion channels

-NT binds on the ion channel causing it to open and allowing ions to flow in

Question 35

Changing the Postsynaptic signal: What is the Metabotropic receptor?

Answer 35

-An indirect method more common than Ionotropic

-Has a slower response requiring more energy and is more varied (i.e., different types)

-The receptor on the surface of the brain is not directly the ion channel itself

-Receptor will receive the ligand and activate the G protein receptor causing a chain reaction (different in different cells/brain areas)

-Will send a message to the ion channel causing it to open and allow ions in to the postsynaptic cell (returns to a new cycle of action potential generation like at the start of flashcards)

Question 36

What can be 2 fates of the neurotransmitter to allow communication to cycle?

Answer 36

1. Reuptake: Presynaptic neuron will absorb the NT back in repackaging it as vesicles (not common)
2. Enzymatic degradation: Acetylcholinesterase
   Acectylcholine –> choline + acetate (more common method)
   -NT is broken down into its constituent parts by a deactivating enzyme
   -These parts are reabsorbed by the presynaptic neuron to be made into NTs again and repackaged into vesicles
   -Means it won’t float around and have an impact after the AP has hit the dendritic button (and instead increases specificity)

Question 37

What are Autoreceptors?

Answer 37

-Receptors located on the presynaptic neurone

-They bind to their neurone’s own NT and they are located in the presynaptic membrane

-Autoreceptors do NOT control ion channels and are ALWAYS metabotropic (indirect)

-Autoreceptors control internal processes including the synthesis and releasing of NTs (decides whether to upregulate or downregulate e.g.,)

-Important for plasticity

Question 38

How do drugs affect neurotransmission?

Answer 38

Drugs (therapeutic or recreational) broadly alter neurotransmitter functioning in one of two ways:

-Agonists: Mimics NTs to similarly fit our receptor to cause activation

-Antagonists: Makes something to fit receptor to block NT from binding (not mimic it) to stop activation

Question 39

What is Brain Plasticity?

Answer 39

Refers to changes in the micro (cellular e.g., connection of one neuron synapsing with another) and macro (global e.g., gyri of the brain) structures of the brain (can also be known as neural plasticity/neuroplasticity)

-Changes result from alterations in neural pathways and synapses

Brain plasticity changes are a natural part of our growth and development. But they also occur:
-In response to learning
-Changes in our behaviour or the environment
-May arise following brain or bodily injury

Question 40

Plasticity: What is some Historical Perspective of the immutable (unchanging) brain?

Answer 40

-Traditional view (until 70’s) of medical science was that brain structure remained relatively immutable (unchangeable) after a critical period of development during early childhood.

-Now research evidence supports the theory that many aspects of brain structure and function are plastic and alterable in adulthood

The degree of plasticity is the subject of considerable research:
-Differs across individuals (genetics?)
-Across the lifespan
-From brain region to region etc.,

Question 41

Who first discovered “Brain Plasticity”?

Answer 41

-William James (1842-1910) N American psychologist and philosopher wrote Principles of Psychology textboox

-Believed brain functions are not fixed throughout life (Principles of Psychology, 1890)

-Backed this up with anecdotal evidence e.g., people in their 40s who uptook piano learning (throws out the immutable brain hypothesis)

Question 42

What reasons may necessitate brain plasticity? Why might this lead to varied mechanisms?

Answer 42

-Brain development (start of lifespan)
-Degeneration (end of lifespan)
-Brain or body injury
-Learning (change in structure as a result of changing functional demand)

-Brain plasticity likely utilises some distinct and overlapping mechanisms to elicit these various changes in brain structure

Question 43

What is the Hebbian Theory? (also can be known as Hebb’s Law or Hebbian Learning)

Answer 43

-Donald Hebb (1904-1985), Canadian Psychologist

-He postulated that brain structure could be adapted as a result of its function (i.e., the physical properties of the brain would change due to functional demand)

-“…two cells or systems of cells that are repeatedly active at the same time will tend to become ‘associated’ so that activity in one facilitates activity in the other.” (1949)
Hebb, D. O. (1949). The organization of behavior: a
neurophyscological theory. New York: Wiley. Science,
173, 652–654.

-“Neurons that fire together, wire together. Those out of sync fail to link” (hijacked 1949 paper more recently and is overly simplistic) (Hebb was actually saying that things become associated so that one facilitates activity in the other)

-Importantly, this refers to SYSTEMS as well as CELLS (systems or cells that work together become associated)

Question 44

Brain Development: What are some structural changes in the ‘growing’ brain?

Answer 44

-Neuroplasticity is any change in neuronal form or function

-Foetal brains contain 30-60% more axons than adult brains

-Research using structural and MRI scanning shows going chronologically and as the brain matures, our brains become less dense with grey matter

Question 45

What is Synaptic Pruning?

Answer 45

-At birth each neuron in the babies cerebral cortex has approximately 2500 synapses per neuron

-This number rapidly expands in a period of post-natal development as babies brain is flooded with sensory information. Peaking in young children (roughly 5-7) up to 15,000 synapses per neuron

-As we progress towards adulthood the number of synaptic connections are steadily reduced

-The resulting synaptic connections are more efficient

-Pruning may represent the learning process and can occur (to a lesser extent than childhood) throughout the lifespan

-Following Hebb’s theory: Synapses that are frequently used have strong connections whereas those that are rarely used are eliminated

Question 46

What is Synaptic Sprouting?

Answer 46

-The creation of new synapses requires growth of new pathways

-For example, after the death of cell A, cell B generates new dendrites to foster a connection with the isolated neuron in place of cell A (this particular example is dendritic sprouting)

-This is useful when we need to forge new brain pathways e.g.,following a lesion in the brain caused by a stroke (additionally, function of old cell can be maintained as other cell can now communicate with it)

Question 47

How do Glial cells play an important role in neuroplasticity?

Answer 47

-Research compared activity of neurones

-Yellow dots signify synapses Glial cells provide the ‘scaffolding’ to promote formation of new synapses as a critical building block (See Todd et al., 2006 J Physiol. Paris)

-Experiments involve using a specific agent to wash glia from a slide so we can stain the slide for synapses

-Glial cells also play a similar role in synaptic pruning

Question 48

What is Synaptic Plasticity?

Answer 48

It’s the changes in the strength of connections between synapses (i.e., changing its performance):
-Long-term potentiation (LTP)
-Long-term depression (LTD)

-Increased or decreased activity leads to changes in synaptic transmission to potentiate (upregulate, LTP) or depress (down-regulate, LTD) the synapse depending on the frequency of use

The ways this may happen includes:
-Altering the number of receptors in membranes and number of vesicles active
-Changes in which proteins are expressed inside the cell

-It is affected by autoreceptors

Question 49

How is the brain reorganised?

Answer 49

-Synaptic plasticity, sprouting and pruning occur at the cellular level of the neuron

-However, cellular changes can have far reaching consequences

-The brain is also organised into functional systems e.g., sensory information from certain parts of the body projects to specific regions of the cerebral cortex (the post central gyrus aka the somatosensory cortex)

-This leads to a cortical representation of the body resembling a map of our body (or Penfield’s homunculus)

-Drastic functional changes (e.g., post amputation) causes re-organisation of homunculi (this questions is the degree of neuroplasticity a good or bad thing?)

Question 50

What evidence is there for plasticity in relation to learning and memory?

Answer 50

Maguire et al (2000):
-Experienced taxi drivers found to have larger hippocampi than novices and controls (fantastic spatial awareness in London)

-The knowledge exam dictates a taxi driver being qualified and they would do better compared to controls (Maguire, Gadian et al., 2000 have a correlation showing the longer they spent in the job the bigger the hippocampus with the more knowledge required)

-This area is associated with memory and grew as they spent more time in the job, but shrunk when they retired

-This study is unlikely to be replicated as we now have Google Maps and Smartphones so less knowledge needed

Question 51

What evidence is there to demonstrate that learning modulates brain plasticity changes?

Answer 51

-Musicianship requires motor learning and improved brain communication, e.g., somatomotor + auditory processing to play in time

Piano expertise requires:
-Bimanual coordination
-Integration of information from separate brain networks

-MRI research to compare experts and novices, or to evaluate people as they learn a skill

-Expert pianists have increased grey matter density in somatomotor hand and motor area both post and pre-central gyrus and auditory cortices (Gaser & Schlaug, 2003)

Question 52

Learning modulates brain plasticity changes: What changes in the brain was found in Expert Pianists?

Answer 52

-They demonstrate increased corpus callosum (CC) volume (i.e., is thicker due to greater bimanual coordination needed)

CC represents the white matter bundle that supports fast transmission of information between the hemispheres:
-Fine-tuned transfer between hemispheres
-Faster conduction speed

-This has been replicated many times (Since Schlaug 1995)

-Interestingly, musicians who begin learning before the age of 7 have the greatest volumes

Question 53

What evidence is there for functional development?

Answer 53

Pascual-Leone et al’s (1993) Braille readers:
-Mapped motor cortex representations of reading finger using EEG and electrical simulation to tip of finger to look at your electrode to where the stimulation is registered on the scalp and how big that signal is (Braille readers and controls)

-Cortical representation of reading finger sensitivity is significantly enlarged in the homunculus at the expense of other fingers in Braille readers

-Can even observe changes within a day when Braille is practised for 4-6 hours (Pascual-Leone et al., 1995)

Question 54

Clinical Implications: What are Phantom Limbs?

Answer 54

-A phenomena experienced by people who have undergone limb amputations

-Cortical reorganisation appears to play an important role in phantom limb sensation (face area tends to start expanding from dormant area)

-Sensations differ between amputees e.g., feelings of a little hand, long hand etc.,

Question 55

Clinical Implications: How prevalent is Phantom Limb pain and what may be the origin of it?

Answer 55

-Phantom limbs are commonly associated with severe chronic pain which does not respond well to standard treatments as it’s driven by neural plastic processes within their brain

-It occurs in at LEAST 90% of limb amputees

Pain following amputation may have a central origin:
-It stems from within the CNS
-Maybe as a result of extreme plastic changes post-amputation
-This is a form of maladaptive plasticity (i.e., hard to treat)

Question 56

Clinical Implications: What is Mirror Box Therapy? (V.S. Ramachandran et al., 1996, 2009)

Answer 56

-The patient places good limb into one side of the box and the amputated limb is obscured on the other side

-The patient sees a reflection of the good hand where the missing limb would be

-The patient receives artificial visual feedback that the absent limb is now moving and obeying commands when they move the ‘good limb’ in synchrony e.g., clench unclench

-This renewed autonomy can reduce maladaptive neuroplastic changes and result in pain relief and is a low tech solution

Question 57

Clinical Implications: What is Maladaptive Plasticity and Central Sensitisation?

Answer 57

MP-it describes plastic changes in the brain that can have negative behavioural or clinical outcomes e.g., Chronic Pain

CS-Prolonged activation of pain pathways can lead to the system becoming overly sensitive and hyperactive and could cause long-term potentiation in the spinal cord. Eventually, this activity will maintain itself and prolong sensations of pain after the original source of pain has gone.

Question 58

Clinical Implications: What is a stroke and what effects can it have?

Answer 58

-It is a blockage which caused reduced blood and oxygen supply resulting in cell death in a part of the brain (aka a lesion)

-A lesion will block neuronal pathways resulting in functional deficits

-The symptoms depend on the function relevant to the area

-Muscle weakness, motor disorders (apraxia), speech (dysarthia), language (aphasia’s) or cognitive deficits are all common (pain is common for thalamic stroke too)

Question 59

Clinical Implications: How can our brain form Secondary Neural Pathways after a Stroke?

Answer 59

-After a lesion in the CNS, neuronal pathways are either blocked or destroyed

1.We can develop secondary neuronal pathways to send neuronal signals around the blockage to maintain function (e.g., sprouting) (like a road blockage)

2.Secondary neuronal pathways pre-exist the lesion, but become “unmasked” in the acute phase (e.g., synaptic plasticity - upregulation)

-It accords with Hebb’s Law, the desired changes in synaptic efficiency, new synapses and sprouting are dependent on activity

Question 60

Clinical Implications: How can we promote the development of good secondary neural pathways post-stroke?

Answer 60

Taub et al (1993) studied patients with strokes leading to poor function of one upper limb

Aims:
-To foster adaptive plastic changes in line with recovery
-To minimise maladaptive changes which could prevent recovery of function

Method:
-Discourage patients from using their good limb
-Therefore, encourage practised uses of dysfunctional limbs

Results:
-Significant improvement in motor function after 2 weeks lasting up to 2 years

Question 61

Clinical Implications: What us Constraint-Induced Movement Therapy (CIMT)?

Answer 61

-This therapy builds on Taub’s theory

-Restrain the unaffected limb and promote intensive use of the affected limb to maintain function after the lesion

-Types of restraints include sling, triangular bandage, splint and mitt

-CIMT is done for 90% of patient waking hours

-Receiving CIMT early (3-9 months post-stroke) results in greater functional gains than receiving delayed treatment (15-21 months post-stroke)

-CIMT brings about benefits by promoting adaptive plasticity in the affected brain hemisphere - more effective when adopted earlier in the recovery process