Module 2 Continued

Question 1

Receptors may be what?

Answer 1

Pre and Postsynaptic, Extra-synaptic, Perisynaptic , Excitatory and Inhibitory or Fast and Slow

Question 2

What are the Ligands of GPCR’s?

Answer 2

Neurotransmitters (GABA, Acetylcholine, Dopamine), Hormones and Sensory signals (Light, Odours and Taste, Many others

Question 3

What type of receptors are GPCR’s?

Answer 3

Metabotropic receptors with 7 Transmembrane domains.

Question 4

In GPCR’s what are Ligand-Receptor interactions mediated by?

Answer 4

G proteins, Trimeric GTP-binding proteins, Dissociation into two components upon activation, act as Dimers

Question 5

G protein activation leads to the activation of what membrane bound enzymes and the regulation of what secondary messengers?

Answer 5

Adenylyl Cyclase’s (Generates cAMP-activates protein kinase A), Phosphodiesterase’s (Hydrolysis of cAMP-negative regulation), Phospholipases (Hydrolysis of membrane phospholipids, generation of DAG and IP3-relase of Ca from internal stores)

Question 6

What do D1 type (D1 and D5) receptors do?

Answer 6

are coupled to GPCR’s and stimulate adenylate cyclase to generate excitatory neurotransmission

Question 7

What do D2 type (D2, D2 and D4) receptors do?

Answer 7

Coupled to Gi/Go GPCR subunits and inhibit adenylate cyclase to mediate inhibitory neurotransmission

Question 8

What is an example of Enzyme linked receptors?

Answer 8

Receptor Tyrosine Kinases

Question 9

What are properties of Enzyme Linked Receptors?

Answer 9

Cytosolic domain with intrinsic enzyme activity or Direct association with an enzyme

Question 10

What is TrkB (Tropomyosin Receptor Kinase B)?

Answer 10

It is a Enzyme Linked Receptor found in Glia, Neuronal Cell Bodies, Presynaptic terminals and Dendrites

Question 11

What is one TrkB’s ligands?

Answer 11

Brain Derived Neurotrophic Brain Factor (BDNF)

Question 12

What is BDNF?

Answer 12

Binds to TrkB receptors, Is packaged in LDCV’s and is a neurotrophin, Neuropeptide and a neuromodulator

Question 13

BDNF is process into what?

Answer 13

proBDNF (signalling molecule associated with Apoptosis and LTP), and matureBDNF (signalling molecule associated with cell survival and LTP)

Question 14

Are enzyme linked receptors slow or fast?

Answer 14

slow

Question 15

What do enzymes linked receptors act on?

Answer 15

second messenger pathways, ligan and voltage gated ion channels (indirectly), local protein synthesis and gene expression

Question 16

What is the synthesis process of GABA?

Answer 16

GABA is an amino acid but isn’t found in proteins, synthesized in gabaminergic neurons glutamic acid decarboxylades (GADs),

Question 17

GABAa Receptors are found where?

Answer 17

Limbic system, Eye, Amygdala, Neurons, Oligodendrocytes, Schwann cells and neuromuscular Junction

Question 18

What is the Structure of GABAa receptors?

Answer 18

multiple possible subunits form pentameric chloride ions.

Question 19

The activation of GABAa receptors causes what?

Answer 19

The activation of GABA or Glycine gated ion channels generate IPSP via the opening of Cl ions causing a Cl influx at the pre and postsynaptic sites resulting in the inhibition of target cells.

Question 20

What forms of inhibition results from GABAa activation?

Answer 20

Tonic Inhibition: ambient extracellular GABA binds to extra synaptic GABAaRs and modulates resting membrane potentials and cell excitability

Question 21

What are drugs that enhance GABA action are known as what?

Answer 21

Anxiolytics

Question 22

Where are acetylcholine receptors found?

Answer 22

Neuromuscular Junction, Autonomic ganglia, postganglionic parasympathetic synapses, interneurons in striatum and cortex, Midbrain, cortex, hippocampus and amygdala

Question 23

What are the two forms of acetylcholine receptors?

Answer 23

Muscarinic Ach (Metabotropic) and Nicotinic Ach (Ionotropic)

Question 24

What are the properties of Muscarinic Ach Receptors?

Answer 24

Sensitive to mAchR, G Protein Coupled, Metabotropic and found in e.g. Glia, Heart muscles and Salivary Glands

Question 25

What are the Properties of Nicotinic AchR?

Answer 25

Sensitive to Nicotine, Ligand Gated ion channel, Mediates fast synaptic transmission, occur at high density at neuromuscular junction

Question 26

What is the synthesis and Degradation process of Ach?

Answer 26

Choline taken up in nerve terminal, Ach synthesized by choline acetyltransferase, Ach transported into vesicles, following synaptic release Ach degraded by Acetylcholinesterase.

Question 27

What are common invertebrate models in neuroscience?

Answer 27

Drosophila melanogaster and Aplysia Californica

Question 28

What are the advantages of the Drosophila melanogaster model?

Answer 28

Small genome and rapid life cycle, small nervous system, easy to identify and circuits

Question 29

what are the advantages of the Aplysia Californica model?

Answer 29

Small nervous system, Large neurons, Easy to identify individual neurons and circuits

Question 30

What is the Siphon-gill-withdrawal reflex?

Answer 30

Tactile stimulus to siphon causes gill withdrawal, Reflex undergoes habituation of sensitization when a noxious stimuli is applied

Question 31

What is the difference between habituation and sensitization?

Answer 31

Habituation: learning to ignore a stimulus that lacks meaning, Sensitization: enhanced response to stimuli

Question 32

Presynaptic Facilitation results in what?

Answer 32

stimuli results in increased sensitivity of the gill-withdrawal response, Noxious stimuli activate interneuron L29, this enhances neurotransmitter release from the sensory neuron presynaptic terminal but with sufficient stimuli can alter gene expression

Question 33

What effect does Protein Kinase A have in Presynaptic facilitation?

Answer 33

increases phosphorylation of K+ channels, increased mobilisation of synaptic vesicles, increased phosphorylation of Ca channels.

Question 34

What are long lasting changes as a result of Presynaptic Facilitation?

Answer 34

Higher levels of cAMP, Activates PKA, which moves to the nucleus causing altered gene expression, new proteins stimulate synapse growth, created a strengthened network

Question 35

What does the hippocampus play an important role in?

Answer 35

memory and learning

Question 36

What is the trisynaptic circuit of the hippocampus?

Answer 36

Entorhinal cortex -> Dentate gyrus synapses -> CA3 synapses -> CA1 Synapses

Question 37

What is long term Potentiation?

Answer 37

Elicited in regions of the brain associated with long term memory, synaptically located, specific to active synapses, associative and persistent

Question 38

What is in vitro?

Answer 38

Studying cells in a culture, Acute brain slices (e.g. hippocampal slices), organotypic brain slices

Question 39

What are properties of Ligand gated ion channels?

Answer 39

fast, excitatory, can open to allow influx or efflux of ions.

Question 40

what are two types of ionotropic glutamate receptors?

Answer 40

AMPA receptors and NMDA receptors

Question 41

What are AMPA receptor properties?

Answer 41

Ligand Gated, Mediates fast depolarization, Na+ channel

Question 42

What are NMDA receptor properties?

Answer 42

Ligand and Ion gated, bind glutamate, require depolarization to remove Mg from channel, slightly slower response, Ca or Na channel

Question 43

What is the AMPA subtype receptor?

Answer 43

AMPAR - GluA1-4, Assemble as dimer to dimer to form hetero-tetrameric receptors or homomeric receptors

Question 44

How are AMPAR receptors regulated?

Answer 44

GluA2 subunits undergo RNA editing (Glutamine-arginine prevents Ca influx, GluA2 containing AMPAR's are Ca impermeable GluA2 lacking AMPAR's are Ca permeable (GluA1 homomeric receptors). Phosphorylation of GluA1 by CaMKll (Serine 831 enhances single channel conductance). Phosphorylation GluA1 by PKA (Serine 845 enhances retention at plasma membrane).

Question 45

What are the four types of Neurotransmitters?

Answer 45

Type 1:Classical (Amino acids) - Glutamate (excitatory), GABA and Glycine (Inhibitory) found in SSV's. Type 2 amines and purines: Acetylcholine, Catecholines, histamine and serotonin, found in SSV's. Type 3 Neuropeptides: Opioids, Substance P neuropeptide Y, found in LDCV's. Type 4 Gases: NO and CO.

Question 46

What are the properties of NO as a neurotransmitter and modulator?

Answer 46

Control of the synthesis of NO is important to regulating its activity. NO is synthesized on demand. NO diffuses from nerve terminals and diffuses into cells. Activates secondary messengers, Inactivated by interaction with substrate.

Question 47

How are AMPAR's dynamic?

Answer 47

AMPAR's shuttle in and out of synapses and are laterally mobile along the cell surface between synaptic and extra synaptic regions. Increased retention and trafficking to PSD.

Question 48

What is the local protein synthesis process of AMPAR's?

Answer 48

Polyribosomes are found in spines, Polyribosomes translocate from dendritic shafts to spines in response to activity. mRNA is found in dendrites and is translated in response to activity

Question 49

How is synaptic strengthening achieved?

Answer 49

Phosphorylation of GluA1. Increased trafficking and retention to PSD. Increased association with regulatory molecules. Retrograde messengers. Glutamate receptors are synthesized locally from pre existing mRNA. Altered gene expression.

Question 50

What is Alzheimer's disease?

Answer 50

A slow developing neurodegenerative disease. Manifests as progressive loss of memory, cognition and language. Characterised by phosphorylation of intracellular hyper-phosphorylated tau and extracellular amyloid-beta plaques.

Question 51

What are the four possible side effects of amyloid beta phosphorylation inf Alzheimer's?

Answer 51

1. A-beta causes an initial hyperexcitability of neurons. 2. A-beta disrupts actin dynamics 3. A-beta interacts with adhesion molecules 4. A-beta induced endocytosis of the AMPA-type glutamate receptors.