Lecture 1: Intro

Question 1

What is resting membrane potential?

Answer 1

The difference in electrical charge between the inside and outside of a cell (neuron)

Question 2

How is resting membrane potential measured?

Answer 2

Electrodes placed in and out of the cell.

• both electrode tips in extracellular fluid, voltage difference 0
• insert tip of intracellular electrode in neuron difference is -70mV

(potential inside neuron is 70mV less than outside)

Question 3

What is a neurons resting potential?

What does this mean

Answer 3

-70mv

The potential inside neuron is 70mV less than outside/ extracellular fluid - the neuron is polarised during this resting state

Question 4

How big are the electrodes used to measure potential of neurons…

Answer 4

Microelectrodes

tips are less than one thousandth of a millimetre in diameter (too small for human eye to see)

must be fine enough to pierce the neural membrane without severely damaging it

Question 5

Ionic basis of resting potential

Answer 5

Salts in neural tissue separate into positively and negatively charged particles (ions)

• Resting potential results from the ratio of negative to positive charges being greater inside neuron than outside

Question 6

What are the factors acting on the equal distribution of ions throughout intracellular and extracellular fluids?

Answer 6

2 factors act to distribute ions evenly between intracellular and extracellular fluid, and 2 features of the neural membrane counteracts these homogenising effects

Question 7

What are homogenising effects?

Answer 7

blending - factors acting to equally distribute ions throughout intracellular and extracellular fluids

Random motion and electrostatic pressure

Question 8

What is random motion?

Answer 8

Random motion:

Ions in neural tissue are in constant random motion, tend to become evenly distributed, are more likely to move from areas of high concentration to low (and vice versa), down concentration gradients

Question 9

What is electrostatic pressure?

Answer 9

Electrostatic Pressure:

Any accumulation of charges in one area tends to be dispersed by the repulsion among the like charges in the vicinity and the attraction of opposite charges in concentrated areas

Question 10

Despite homogenising effects of random motion and electrostatic pressure…

Answer 10

no single class of ions is distributed equally on the two sides of the neural membrane

Question 11

4 kinds of ions contributing to resting potential (-70mv)

Answer 11

Na+, K+, Cl- and various negatively charged protein ions

Question 12

Which ions are more concentrated outside the neuron than inside?

Answer 12

Na+ and Cl- concentrations are greater outside a resting neuron than inside

Question 13

Which molecules are more concentrated inside the neuron than outside?

Answer 13

K+ ions are more concentrated inside

Negatively charged protein ions are synthesised inside neuron and mostly stay there

Question 14

What are the neural membrane properties that counteract homogenising effects of random motion and electrostatic pressure?

Answer 14

Differential permeability to ions

Sodium-Potassium Pump Transporter

Question 15

Differential permeability to ions…

Which ions can fit through the membrane?

Answer 15

Differential permeability to ions:

• K+ and Cl- ions pass readily through neural membrane
• Na+ ions pass through it with difficulty
• negatively charged proteins do not pass through

ions pass through specialised ion channels

Question 16

Sodium-Potassium pump transporter…

Answer 16

Sodium-Potassium Pump Transporter:

Transport of Na+ ions OUT of neurons and transport of K+ ions IN is an energy-consuming mechanism in cell membrane

continually exchanges 3 Na+ inside neuron for 2 K+ outside

• Pump only plays a minor role in the reestablishment of the resting potential

Question 17

Alan Hodgkin and Andrew Huxley

Answer 17

In 1950’s provided first evidence that an energy-consuming process is involved in the maintenance of the resting potential

• Calculated for each ion the electrostatic charge that would be required to offset the tendency for them to move down their concentration gradients
• Found K+ ions are continuously driven out of resting neuron by 20mV pressure and that despite high resistance off the cell membrane to the passage of Na+ ions, they are continuously driven in by 120mV of pressure –> Active mechanisms in cell membrane counteract influx of Na+ ions by pumping Na+ ions out as rapidly as they pass in and to counteract the efflux of K+ ions by pumping K+ ions in as rapidly as they pass out

Question 18

What are transporters?

Answer 18

Transporters: Mechanisms in the membrane of a cell that actively transport ions or molecules across the membrane

Question 19

Factors responsible for maintaining the differences in intracellular and extracellular concentrations in resting neurons

Na+

Answer 19

• Driven into neurons by high conc of Na+ ions outside neuron and negative internal resting potential of -70mV
• Membrane is resistant to passive diffusion of Na+, sodium-potassium pump able to maintain high external conc of Na+ ions by pumping them out at same slow rate as they move in

Question 20

Factors responsible for maintaining the differences in intracellular and extracellular concentrations in resting neurons

K+

Answer 20

• K+ ions move out neuron because of high internal conc, tendency partially offset by internal negative potential
• Leave neuron at substantial rate as membrane offers little resistance to passage
• To maintain high internal concentration of K+ ions sodium-potassium pump pumps K+ ions into neurons at same rate as they move out

Question 21

Factors responsible for maintaining the differences in intracellular and extracellular concentrations in resting neurons

Cl-

Answer 21

• Little resistance in neural membrane to passage, readily forced out neuron by negative internal potential
• Accumulate on outside, increased moving down conc gradient back into neuron
• When electrostatic pressure for Cl- ions to move out is equal to tendency for them to move back in, distribution is at equilibrium, which occurs at -70mV

Question 22

Generation of postsynaptic potentials

Answer 22

When neurotransmitter molecules bind to postsynaptic receptors, depending on the structure of both neurotransmitter and the receptor they may depolarise the receptive membrane (decrease the resting membrane potential from -70 to -67mV for example) or they may hyperpolarise it (increase the resting membrane potential from -70 to -72mV for example)

Question 23

What is an ESPS?

Answer 23

Excitatory Postsynaptic Potentials (Postsynaptic Depolarisation)
- Increase likelihood neuron will fire

Question 24

what is a IPSP?

Answer 24

Inhibitory Postsynaptic Potentials (Postsynaptic Hyperpolarisations)
- Decrease likelihood neuron will fire

Question 25

Features of ESPS and ISPSs

Answer 25

Both are graded responses; amplitudes are proportional to the intensity of the signals that elicit them
- Weak signals elicit small postsynaptic potentials, strong elicit large ones

Both travel passively from sites of generation at synapses, transmission is rapid (assumed instantaneous), duration of each can vary considerably

Transmission is decremental, both decrease in amplitude as they travel through the neuron

Most of both do not travel more than a couple of mm from their site of generation before they fade out (never travel far along axon)

Question 26

Integration of Postsynaptic Potentials and Generation of Action Potentials

Answer 26

• Postsynaptic potentials created at a single synapse typically have little effect on the firing of the postsynaptic neuron
• Whether or not a neuron fires depends on the balance between the excitatory and inhibitory signals reaching its axon
• EPSP’s and IPSP’s travel to the axon hillock (decrementally and instantly) and are generated in the adjacent section of the axon
• If the sum of depolarisation and hyperpolarisations is sufficient to depolarise the membrane to a level of excitation (-65mV) an action potential is generated near the axon hillock
• Action potential lasts 1 millisecond (reversal of membrane potential from -70 to +50mV)
• Action potentials are not graded responses; magnitude is not related to the intensity of the stimuli that elicit them
• They are all or non-responses, either elicit occur to their full extent or do not occur at all
• ->Each multipolar neuron adds together all the graded excitatory and inhibitory postsynaptic potentials reaching its axon and decides to fire or not on the basis of their sum

Question 27

Integration:

Answer 27

Adding or combining a number of individual signals into one overall signal

Question 28

Spatial Summation:

Answer 28

Local postsynaptic potentials produced simultaneously on different parts of the receptive membrane sum to form a greater potential, simultaneous ESPSs and IPSPs sum to cancel each other out

Question 29

Temporal Summation:

Answer 29

postsynaptic potentials produced in rapid succession at the same synapse sum to form a greater signal

Stimulations of a neuron can add together over time, effect of the second stimulus will be superimposed on the lingering postsynaptic potential produced by the first

-Possible for a brief subthreshold excitatory stimulus to fire a neuron if it is administered twice in rapid succession, possible for IPSP activated twice in rapid succession to produce a greater IPSP than that produced by a single stimulation

Question 30

Ionic Basis of Action Potentials:

Answer 30

1. Voltage-activated sodium channels in the axon membrane open wide, Na+ ions rush in suddenly, membrane potentials change from –70mV to +50mV
2. Rapid change triggers opening of voltage activated potassium channels
3. K+ ions near membrane are driven out of cell through potassium channels first by high internal conc then when action potential is near its peak by the positive internal charge
4. After 1 millisecond sodium channels close, marks end of rising phase of AP and beginning of repolarisation by continued efflux of K+ ions
5. Once repolarisation has been achieved the potassium channels gradually close meaning too many K+ ions flow out of neuron, it is left hyperpolarised for a brief period of time
6. AP involves only ions right next to membrane, single action potential has little effect on relative concentrations of ions inside and outside neuron, any effect is also rapidly re-established by random movement of ions

Question 31

Refractory Periods:

Answer 31

• Brief period 1-2ms after initiation of AP during which it is impossible to elicit a second one until it has been repolarised
• Absolute refractory period is followed by relative refractory period (period during which it is possible to fire the neuron again but only by applying higher than normal levels of stimulation)
• End of the relative refractory period is point at which amount of stimulation necessary to fire a neuron returns to baseline
• Refractory period is responsible for the fact that APs normally travel along axons in only one direction (portions of axon over which an AP has just travelled are left momentarily refractory, AP cannot reverse direction)
• Refractory period also responsible for the fact that the rate or neural firing is related to the intensity of the stimulation
• If level of stimulation is of intensity just sufficient to fire neuron when it is at rest, neuron does not fire again until both the absolute and relative refractory periods have run their course
• Intermediate levels of stimulation produce intermediate rates of neural firing
• High level of continual stimulation, neuron fires again as soon as its absolute refractory period is over

Question 32

Axonal Conductance of Action Potentials:

Answer 32

Conduction of APs along an axon differs from conduction of EPSPs and IPSPs

• Conduction is nondecremental, do not grow weaker as they travel along axonal membrane
• APs are conducted more slowly than postsynaptic potentials

Reasoning: Conduction of ESPSs and IPSPs is passive whereas axonal conduction of action potentials is active (ion process)

Question 33

Antidromic Conduction:

anti - opposed to or against

Answer 33

If electrical stimulation of sufficient intensity is applied to the terminal end of an axon an AP will be generated and travel along the axon back to the cell body

(Conduction along the axon away from the axon terminals towards the soma, often induced experimentally - in reverse direction)

Question 34

Orthodromic Conduction:

ortho - right or correct

Answer 34

Axonal conduction in the natural direction from cell body to terminal buttons

Question 35

Conduction in Myelinated Axons:

Answer 35

• Ions can pass through the axonal membrane only at nodes of Ranvier- gaps between adjacent myelin segments
• Axonal sodium channels are concentrated at the nodes of Ranvier, when an AP is generated in a myelinated axon the signal is conducted passively (instantly and decrementally) along the first segment of myelin to the next node of Ranvier
• Signal is somewhat diminished by the time it reaches the node but it is still strong enough to open the voltage-activated sodium channels at the node to generate another full-blown action potential
• Myelination increases speed of axonal conduction, signal jumps from node to node in passive instantaneous action –> Saltatory Conduction
• There is a slight delay at each node whilst AP is actively generated but conduction is still faster than in unmyelinated axons in which passive conduction has less prominent role
• Neurodegenerative diseases that attack myelin effect neural activity e.g. multiple sclerosis

Question 36

Velocity of Axonal Conduction:

Answer 36

• Conduction is faster in large-diameter axons and is faster in myelinated axons e.g. mammalian motor neurons (synapse on skeletal muscles, some can conduct 100meters/second, 224 miles an hour CATS)
• Small unmyelinated axons conduct APs at 1 meter/second
• Maximum velocity of conduction in human motor neurons is 60 meters/second

Question 37

Conduction in Neurons without Axons:

Answer 37

Neurons in the brain have no or very short axons

• Conduction in interneurons is passive and decremental, many do not display action potentials

Question 38

Hodgkin-Huxley Model in Perspective:

Answer 38

• Advanced understanding of neural conduction
• Does not represent variety, complexity and plasticity of many neurons in mammalian brain
• Study was based on squid motor neurons
• Motor neurons are simple, large and readily accessible in PNS, squid motor neurons are particularly large making it difficult to directly apply to mammalian brain
• Model must be applied to cerebral neurons with caution

Properties of cerebral neurons not shared by motor neurons:
• Many cerebral neurons fire continually even when they receive no input
• Axons of some cerebral neurons can actively conduct both graded signals and APs
• APs of all motor neurons are the same but APs of different classes of cerebral neurons vary greatly in duration amplitude and frequency
• Many cerebral neurons have no axons and do not display action potentials
–> Cerebral neurons are more complex than motor neurons

Question 39

Synaptic Transmission: Chemical Transmission of Signals among Neurons

Structure of Synapses:

Answer 39

Neurotransmitter molecules are released from terminal buttons into synaptic clefts where they induce EPSPs or IPSPs in other neurons by binding to receptors on their postsynaptic membranes

Look at a diagram bro

1. Axodendritic Synapses: synapses of axon terminal buttons on dendrites, many terminate on dendritic spines (nodules of various shapes that are located on the surfaces of many dendrites)
2. Axosomatic Synapses: synapses of axon terminal buttons on somas

^^Both are most common synaptic arrangements but there are also…

3. Dendrodendritic Synapses: capable of transmission in either direction
4. Axoaxonic Synapses: mediate presynaptic facilitation and inhibition, an axoaxonic synapse on or near a terminal button can selectively facilitate or inhibit the effects of that button on the postsynaptic neuron, advantage is that they can selectively influence one particular synapse rather than the entire presynaptic neuron

Question 40

2 most common structures of synapses…

Answer 40

1. Axodendritic Synapses: synapses of axon terminal buttons on dendrites, many terminate on dendritic spines (nodules of various shapes that are located on the surfaces of many dendrites)
2. Axosomatic Synapses: synapses of axon terminal buttons on somas

Question 41

2 less common structures of synapses…

Answer 41

3. Dendrodendritic Synapses: capable of transmission in either direction
4. Axoaxonic Synapses: mediate presynaptic facilitation and inhibition, an axoaxonic synapse on or near a terminal button can selectively facilitate or inhibit the effects of that button on the postsynaptic neuron, advantage is that they can selectively influence one particular synapse rather than the entire presynaptic neuron

Question 42

Directed Synapses:

Answer 42

Synapses at which the site of neurotransmitter release and the site of neurotransmitter reception are in close proximity

Question 43

Nondirected Synapses:

Answer 43

Synapses at which the site of release is at some distance from the site of reception, neurotransmitter molecules are release from a series of varicosities (bulges or swellings) along axon and its branches therefore are widely dispersed to surrounding targets.

Due to appearance, synapses are often referred to as string-of-beads synapses

Question 44

Synthesis, Packaging and Transport of Neurotransmitter Molecules:

Answer 44

2 categories of neurotransmitter molecules (small and large)

• Small neurotransmitters are synthesised in cytoplasm of terminal button and packaged in synaptic vesicles by button’s Golgi Complex, once filled with neurotransmitter vesicles are stored in clusters next to presynaptic membrane
• Large neurotransmitters (neuropeptides, short amino acid chains comprising of 36 amino acids, effectively small proteins) are assembled in the cytoplasm of the cell body on ribosomes, are then packaged in vesicles by cell body’s Golgi Complex and transported by microtubules to the terminal buttons at a rate of 40cm/day
• Vesicles containing neuropeptides are larger than those containing small molecule neurotransmitters, do not usually congregate as closely to presynaptic membrane as other vesicles do
• Many neurons contain two types of neurotransmitter (coexistence) most cases involve one small molecule neurotransmitter and one neuropeptide

Question 45

Release of Neurotransmitter Molecules:

Answer 45

Exocytosis: Process of neurotransmitter release

• When neuron is at rest synaptic vesicles containing small molecule neurotransmitters congregate near sections of presynaptic membrane particularly rich in voltage-activated calcium channels, when stimulated by action potentials calcium ion channels open, calcium ions enter causing synaptic vesicles to fuse with the presynaptic membrane and empty their contents into the synaptic cleft
• At many but not all, one AP causes the release of neurotransmitter molecules from one vesicle
• In contrast, neuropeptides are released gradually in response to general increases in the level of intracellular calcium ions, this might occur during a general increase in the rate of neuron firing

Question 46

What is exocytosis?

Answer 46

Process of neurotransmitter release

Question 47

Activation of Receptors by Neurotransmitter Molecules:

Answer 47

Once released, neurotransmitter molecules produce signals in postsynaptic neurons by binding to receptors in the postsynaptic membrane

• Each receptor is a protein that contains binding sites for only particular neurotransmitters
• Neurotransmitter can influence only those cells that have receptors for it
• Any molecule that binds to another is referred to as its Ligand, a neurotransmitter is therefore a ligand of its receptor
• Most neurotransmitters bind to several different types of receptors
• Different types of receptors to which a particular neurotransmitter can bind are called Receptor Subtypes
• Different receptor subtypes are located typically in different brain areas, respond to neurotransmitter in different ways
• Advantage of this is they enable one neurotransmitter to transmit different kinds of messages to different parts of the brain
• Binding can influence postsynaptic neuron depending on whether receptor is ionotropic or metabotropic

Ionotropic Receptors: Receptors associated with ligand-activated ion channels

• When a neurotransmitter binds to an ionotropic receptor, associated ion channel opens or closes immediately inducing an immediate postsynaptic potential e.g. EPSPs (depolarisations) occur because neurotransmitter opens sodium channels, increasing influx of Na+ into neuron and IPSPs (hyperpolarisations) occur because neurotransmitter opens potassium channels or chloride channels increasing efflux of K+ ions or influx of Cl-

Question 48

What is a ligand?

Answer 48

Any molecule that binds to another, a neurotransmitter is therefore a ligand of its receptor

Question 49

What is a receptor subtype?

Answer 49

Different types of receptors to which a particular neurotransmitter can bind

Question 50

What is an ionotropic receptor?

Answer 50

Receptor associated with ligand-activated ion channels

Question 51

What is a metabotropic receptor?

Answer 51

Receptors associated with signal proteins and G proteins

• More prevalent than ionotropic receptors
• Effects are slower to develop, longer lasting, more diffuse and varied
• Many kinds of metabotropic receptors each attached to serpentine signal protein that goes back and forth in cell membrane 7 times
• Metabotropic receptor is attached to a portion of the signal protein outside the neuron, G protein is attached to portion of signal protein inside neuron
• When neurotransmitter binds subunit of associated G protein breaks away
• Depending on particular G protein, subunit may move along inside surface of membrane and bind to a nearby ion channel thereby inducing an EPSP or IPSP, or it may trigger the synthesis is a second messenger (neurotransmitters are considered to be the first messengers). Once created, a second messenger diffuses through cytoplasm and may influence activities of neuron
• May enter the nucleus and bind to DNA influencing genetic expression, neurotransmitter binding to metabotropic receptor can therefore have radical long lasting effects

Autoreceptors: Metabotropic receptors that have 2 unconventional characteristics,
> bind to their neurons own neurotransmitter molecule located on the presynaptic rather than postsynaptic membrane
>usual function - monitor the number of neurotransmitter molecules in the synapse to reduce subsequent release when they are low

Question 52

Summary of small-molecule neurotransmitters and neuropeptides

Answer 52

Differences between small molecule and peptide neurotransmitters in patterns of release and receptor binding suggest that they serve different functions

• Small-molecule neurotransmitters are released into directed synapses and to activate either ionotropic receptors or metabotropic receptors that act directly on ion channels
• Neuropeptides tend to be released diffusely and virtually all bind to metabotropic receptors that act through second messengers
• Function of small-molecule neurotransmitters appears to be the transmission of rapid, brief excitatory or inhibitory signals to adjacent cells
• Function of neuropeptides appears to be the transmission of slow, diffuse, long lasting signals

Question 53

Reuptake, Enzymatic Degradation and Recycling:

Answer 53

If nothing intervened neurotransmitters would remain active in synapse clogging channel of communication
- Reuptake and Enzymatic Degradation are terminating mechanisms

Reuptake: Most common, majority of neurotransmitters once released are drawn back into presynaptic buttons by transporter mechanisms

Enzymatic Degradation: Neurotransmitters are broken apart in the synapse by enzymes (proteins that stimulate or inhibit biochemical reactions without being affected by them) e.g. Acetylcholine is broken down by acetylcholinesterase

-Regardless of mechanism of their deactivation, products of neurotransmitter breakdown are drawn back into button and recycled as are vesicles which are used to create new vesicles

Question 54

Glial Function and Synaptic Transmission:

Answer 54

Glial cells surround neurons and provide support for and insulation between them.

Importance of Glial cells suggested by greater prevalence of these cells in intelligent organisms

• Astrocytes (star shaped glial cell in CNS) release chemical transmitters to contain receptors for neurotransmitters to conduct signals and participate in neurotransmitter uptake
• Brain function is not just neuron-neuron connection

Question 55

Gap Junctions:

Answer 55

Gap junctions are narrow spaces between adjacent neurons that are bridged by fine tubular channels (connexins) that contain cytoplasm

• Cytoplasm of 2 neurons is continuous allowing electrical signals and small molecules to pass from one neuron to the next
• Gap junctions are sometimes called electrical synapses
• They are common in invertebrate nervous systems and mammalian brain, are an integral feature of local neural inhibitory circuits
• Astrocytes have been shown to communicate with each other, neurons and other cells through gap junctions
• Gap junctions are less selective than synapses, communication across them is very fast because it does not involve active mechanisms and gap junctions permit communication in either direction

Question 56

Neurotransmitters:

Small molecule neurotransmitters

Amino acid neurotransmitters:

Answer 56

Neurotransmitters in majority of fast-acting directed synapses in CNS are amino acids

4 most widely studied: GABA, Glutamate, Aspartate and Glycine

• Last 3 are common in proteins we consume; GABA is synthesised by modification of structure of glutamate
• Glutamate is most prevalent excitatory neurotransmitter in mammalian CNS
• GABA is most prevalent inhibitory neurotransmitter however it has excitatory effects at some synapses

Question 57

Small molecule neurotransmitters

Monamine Neurotransmitters:

Answer 57

• Another class of small molecule neurotransmitters
• Each synthesised from single amino acid
• Slightly larger than amino acid neurotransmitters and effects are more diffuse
• Present in small groups of neurons whose cell bodies are located in brain stem
• These neurons have highly branched axons with many varicosities (string of beads synapses) from which monoamine neurotransmitters are diffusely released into extracellular fluid

4 monamine neurotransmitters, Dopamine, Epinephrine, Norepinephrine and Serotonin
> Subdivided into 2 groups, Catecholamines and Indolamines on the basis of their structures

Catecholamines:
- Dopamine, Norepinephrine and Epinephrine are Catecholamines, each synthesised from amino acid tyrosine
> Tyrosine is converted to L-dopa which is converted to dopamine
> Neurons that release norepinephrine have extra enzyme that is not present in dopaminergic neurons which converts dopamine in them to norepinephrine
> Neurons that release epinephrine have all the enzymes present in neurons that release norepinephrine along with an extra enzyme that converts norepinephrine to epinephrine

• Neurons that release norepinephrine are noradrenergic
• Neurons that release epinephrine are adrenergic
• Epinephrine and Norepinephrine were adrenaline and noradrenaline

Indolamines:
- Serotonin (5-hydroxytryptamine, 5-HT) is synthesised from amino acid tryptophan and is classified as indolamine

Question 58

Steps in the synthesis of catecholamines from tyrosine

Answer 58

Tyrosine -> L-dopa -> dopamine -> norepinephrine -> epinephrine

Question 59

Small molecule neurotransmitters

Acetylcholine:

Answer 59

(Ach)

• Small molecule neurotransmitter
• Created by adding acetyl group to a choline molecule
• Neurotransmitter at neuromuscular junctions at many synapses of ANS and CNS

Question 60

Small molecule neurotransmitters

Unconventional Neurotransmitters:

• Soluble-gas neurotransmitters (nitric oxide, carbon monoxide)

Answer 60

(nitric oxide, carbon monoxide)

• Produced in neural cytoplasm, immediately diffuse through cell membrane into extracellular fluid then into nearby cells
• Easily passed through cell membranes as they are soluble in lipids
• Once inside another cell, stimulate production of a second messenger in few seconds and are deactivated by being converted into other molecules
• Difficult to study as only exist for few seconds
• Soluble-gas neurotransmitters are involved in retrograde transmission
• At some synapses, transmit feedback signals from the postsynaptic neuron back to the presynaptic neuron
• Function seems to be to regulate activity of presynaptic neurons

Question 61

Small molecule neurotransmitters

Unconventional Neurotransmitters:

• Endocannabinoids

Answer 61

• Neurotransmitters that are similar to delta-9-tetrahydrocannabinol (THC), the main psychoactive constituent of marijuana
• 2 types, Anandamide is most widely studied (Ananda, eternal bliss)
• Produced immediately before they are released
• Synthesised from fatty compounds in cell membrane
• Released from dendrites and cell body
• Have most effects on presynaptic neurons inhibiting subsequent synaptic transmission

Question 62

Large molecule neurotransmitters

Neuropeptides:

Answer 62

• Over 100 identified
• Actions depend on amino acid sequence
• Group into 5 categories, 3 of which acknowledge neuropeptides function in multiple capacities not just as neurotransmitters

> Pituitary Peptides: Contains neuropeptides that were first identified as hormones released by the pituitary gland

> Hypothalamic Peptides: Contains neuropeptides first identified as hormones released by the hypothalamus

> Brain-gut Peptides: Contains neuropeptides hat were first discovered in the gut

• Opioid Peptides: Contains neuropeptides similar in structure to active ingredients of opium
• Miscellaneous Peptides: Catch all category containing all the neuropeptide transmitters that do not fit into one of the other 4 categories

Question 63

What are the 5 categories of neuropeptide neurostransmitters?

Answer 63

1. Pituitary Peptides
2. Hypothalamic Peptides
3. Brain-gut Peptides
4. Opioid Peptides
5. Misc. peptides

First 3 acknowledge neuropeptides function in multiple capacities not just as neurotransmitters

Question 64

Pharmacology of Synaptic Transmission and Behaviour:

Answer 64

• Drugs facilitate or inhibit synaptic transmission
• Drugs that facilitate are agonists, drugs that inhibit are antagonists
• Agonists of a particular neurotransmitter bind to postsynaptic receptors and activate them whereas some antagonistic drugs (receptor blockers) bind to postsynaptic receptors without activating them and block access of usual neurotransmitter

Question 65

How Drugs Influence Synaptic Transmission:

Answer 65

7 general common steps of neurotransmitters:

1. synthesis of neurotransmitter
2. storage of vesicle
3. breakdown in cytoplasm of any neurotransmitter that leaks from vesicles
4. exocytosis
5. inhibitory feedback via Autoreceptors
6. activation of postsynaptic receptors and deactivation

Question 66

Behavioural Pharmacology: 3 Influential Lines of Research

Wrinkles and Darts – Discovery of Receptor Subtypes:

Answer 66

**Atropine (main active ingredient in belladonna/ deadly nighshade) is a receptor blocker that exerts antagonistic effect by binding muscarinic receptors thereby blocking effects of acetylcholine on them
> Has pupil dilating effects which are mediated by antagonistic actions on muscarinic receptors in PNS
> Large doses of atropine on memory is mediated by antagonistic effect on muscarinic preceptors in the CNS, earliest clue that cholinergic mechanisms play a role in memory

**Curare used on tips of darts to kill, is a receptor blocker at cholinergic synapses but acts at nicotinic receptors, binds and blocks transmission at neuromuscular junction, paralysing recipients and killing them by blocking respiration
> Sometimes administered to humans during surgery to ensure muscles do not contact during incision, patients breathing must be maintained by respirator

**Botox (Botulinium toxin) is a neurotoxin released by bacterium found in spoiled food, is another nicotinic antagonist but it blocks the release of acetylcholine at neuromuscular junction and is a deadly poison
> Injected at specific sites however it has applications in medicine (reduction of tremors) and cosmetic (reduction of wrinkles)

Question 67

Behavioural Pharmacology: 3 Influential Lines of Research

Pleasure and Pain - Discovery of Endogenous Opioids:

Answer 67

**Morphine (major psychoactive ingredient) is highly addictive but is an effective analgesic (painkiller)
> Morphine bind effectively to receptors in the brain
> Receptors generally found in hypothalamus and other limbic areas, most concentrated in area of brain stem around cerebral aqueduct which connects the third and fourth ventricles (periaqueductal gray PAG)
>Microinjection of morphine into PAG or electrical stimulation of PAG produces strong analgesia
> Existence of selective opiate receptors in brain suggest that opioid (opiate like) chemicals occur naturally in the brain

-Several families of endogenous (occurring naturally within the body) opioids have been discovered.

• *Enkephalins (meaning in the head) and Endorphins (endogenous morphine)
• All endogenous opioid neurotransmitters are neuropeptides and their receptors are metabotropic

Question 68

Behavioural Pharmacology: 3 Influential Lines of Research

Tremors and Insanity – Discovery of Anti-Schizophrenic Drugs:

Answer 68

Development in treatment for mental illness

Parkinson’s disease played role in discovery, 2 drugs were discovered to have anti-schizophrenic effects
-Took about 3 weeks to take effect at which point patients displayed mild Parkinson’s symptoms (tremor at rest)

• Researchers discovered that Parkinson’s disease is associated with the degeneration of the main dopamine pathway of the brain and that dopamine agonists (cocaine, amphetamines) produce a temporary disorder that resembles schizophrenia
• Suggested schizophrenia is caused by excessive activity at dopamine synapses and that potent dopamine antagonists would be effective in its treatment
• D2 receptor plays key role in schizophrenia and drugs that most effectively block it are most effective anti-schizophrenic drugs
• Can help many patients making hospitalisation unnecessary