Session 2 - The Environment of the Brain

Question 1

What are the two main consitutients of the CNS?

Answer 1

Neruones and Glial cells

Question 2

What are the two main roles of neurones?

Answer 2

Sense changes

Communicate with other neurones

Question 3

Give the five roles of glial cells

Answer 3

Support
Nourish
Insulate neurones
Remove waste

Question 4

What are the three main types of glial cell?

Answer 4

Astrocytes
Oligodendrocytes
Microglia

Question 5

What are the four main roles of astrocytes?

Answer 5

Offer structural support
Help to provide nutrition for neurones
Help to remove neurotransmitters
Help to buffer K+ in brain ECF

Question 6

Why is it necessary that astrocytes provide nutrition for neurones?

Answer 6

Neurones cannot store glycogen, and thus get most of their glucose from blood. This causes issues when they need a LARGER supply of energy

Question 7

How do astrocytes provide nutrition for neurones?

Answer 7

Act as a store of glycogen

Produce lactate, which can be transferred to neurones to supplement their supply of glucose

Question 8

How do astrocytes help to remove neurotransmitters?

Answer 8

Uptake spare neurotransmitters from synaptic cleft, removing them from functional circulation.

Question 9

Why is it important astrocytes remove neurotransmitters?

Answer 9

• Helps to stop transmitter spilling over to neighbouring cells
• helps terminate the synaptic response
• Helps to recycle transmitters or breakdown product back to terminal
• Also keeps glutamate levels down, as too much is toxic to neurones

Question 10

HOw is glutmate toxic to neurones?

Answer 10

Causes opening of NMDA receptors, leading to calcium entry - excessive glutamate causes excessive opening and excessive activation

Question 11

How do astrocytes help to buffer K+ in the brain?

Answer 11

K+ ions move out of neurones during repolarisation after an action potential, an event which occurs a huge amount in the brain.
Astrocytes take up K+ via action of Na-K-ATPase

Question 12

What is the role of oligodendrocytes?

Answer 12

Responsible for myelination of axons in the CNS

Question 13

What do microglia do?

Answer 13

o The macrophages of the brain - immunocompetent cells, which recognise foreign material. When activated they phagocytose foreign material and debris.
o Can also act as an antigen presenting cell to T cells.

Question 14

What is the blood brain barrier?

Answer 14

A theoretical dividing walls which exists to maintain the environment of the brain in a steady state, protecting it from extracelluar ion changes, peripheral hormones and drugs. Also prevents circulation neurotransmittes from entering CNS.

Question 15

Outline the structure of th eblood brain barrier

Answer 15

o Endothelial cells of cerebral capillaries have very high resistance tight junctions between them
 Even small ions cannot permeate between the cells
 Also basement membrane of capillaries
o Astrocytes have foot processes that adhere to the capillary endothelial cells, so they are entirely enclosed.
 Also secrete factors that help to maintain the endothelial cell tight junctions

Question 16

What molecules can simply diffuse across the BBB?

Answer 16

Water and lipid soluble molecules can diffuse across

Sustances such as glucose, amino acids and potassium are transported across (conc can be controlled)

Question 17

What is mean by stating that the CNS is immunopriveledged?

Answer 17

Less vulnerable to the vagaries of the immune system

Question 18

Why does the CNS have to be immune privileged?

Answer 18

Rigid skull will not tolerate volume expansion, so too mcuh inflammatory response would be harmful

Question 19

How do immune reactions occur in the CNS?

Answer 19

o Microglia act as antigen presenting cells to T cells, which can enter the CNS via post-capillary venules
o CNS inhibits the initiation of the pro-inflammatory T-cell response

Question 20

Give four main structural features of a neurone

Answer 20

o Cell body (Soma)
o Dendrites
o Axon
o Terminals

Question 21

Outline the course of neurotransmitter release

Answer 21

Opening of Voltage gated Ca2+ channels
The action potential arrives at the presynaptic membrane. This causes the opening of voltage-gated Ca2+ channels and the subsequent influx of calcium ions down their concentration gradient.

Formation of Snare Complex and Neurotransmitter Release
This increase in intracellular calcium concentration leads to Ca2+ binding to Synaptotagmin, leading to the formation of the Snare Complex and Ach release.

Question 22

Give three different classes of CNS neurotransmitters

Answer 22

Amino acids
Biogenic amines
Peptides

Question 23

Give an excitatory amino acid based neurotrasmitter

Answer 23

Glutamate

Question 24

Give an inhibitory amino acid neurotransmitter

Answer 24

GABA (brain) and glycine (Brainstem and Spinal Cord)

Question 25

Give three biogenic amines NTs

Answer 25

 Acetylcholine, Noradrenaline, Dopamine, Serotonin (5-HT), Histamine

Question 26

Give three pepitde NTs

Answer 26

 Dynorphin, enkephalins, Substance P, somatostatin, Cholecystokinin, Neuropeptide Y

Question 27

Give three glutamate receptors

Answer 27

o AMPA Receptor – Ion channel is Na+ and K+ permeable o NMDA Receptor – Ion channel is Ca2+ permeable o Kainate receptor

Question 28

What makes up 70% of CNS synapses?

Answer 28

o Over 70% of CNS synapses o Have both AMPA and NMDA receptors o NMDA receptors need glutamate to bind and the cell to be depolarised to allow Ca2+ entry (and subsequent neurotransmitter release)

Question 29

What is synaptic plasciticity?

Answer 29

Glutamate receptors are thought to have an important role in learning and memory o Activation of NMDA receptors and mGluRs can lead to up regulation of AMPA o Strong, high frequency stimulation can cause Long Term Potentiation (LTP)  This is thought to be the basis of long time synapse strengthening and learning

Question 30

What is excitotoxicity?

Answer 30

o Ca2+ entry through NMDA receptors is important in Excitotoxicity. o Too much Glutamate  Excitotoxicity o Astrocytes take up glutamate from the synaptic cleft to prevent this (see above)

Question 31

What causes inhibition of GABA and glycine receptors?

Answer 31

have integral Cl- ion channels. The opening of these channels causes hyperpolarisation, decreasing action potential firing (inhibitory post-synaptic potential IPSP). o GABAA is the main inhibitory neurotransmitter in the brain, and is bound by barbiturates, benzodiazepines. Both of these enhance channel response to GABA. o Glycine is present in high concentrations in the spinal cord and brainstem

Question 32

Name four biogenic amines

Answer 32

o Acetylcholine, Noradrenaline, Dopamine, Serotonin (5-HT)

Question 33

What do biogenic amines do?

Answer 33

o Mostly act as neuromodulators | o Confined to specific pathways

Question 34

Give three places in which acetylcholine is a neurotransmitter

Answer 34

o Neurotransmitter at neuromuscular junction, ganglion synapse in autonomic nervous system, postganglionic in parasympathetic nervous system

Question 35

What does acetylcholine act on in the CNS?

Answer 35

o In CNS acts on both nicotinic and muscarinic receptors in the brain  Mainly excitatory  Receptors often on presynaptic terminals to enhance the release of other transmitters  Main functions are arousal, learning and memory and motor control

Question 36

Where are the chlinergic pathways in the CNS located?

Answer 36

o Neurones originate in the basal forebrain and brainstem o Diffuse projections to many parts of the cortex and hippocampus o Also local cholinergic interneurons (e.g. corpus striatum)

Question 37

What is the pathology of alzhermiers disease?

Answer 37

o Degeneration of cholinergic neurones in the nucleus basalis of Meynert is associated with Alzheimer’s disease o Cholinesterase inhibitors are used to alleviate symptoms of Alzheimer’s disease

Question 38

Give three pathways in brain involving dopamine

Answer 38

o Nigrostriatal Pathway  Motor control o Mesocortical and Mesolimbic Pathways  Mood, arousal, reward

Question 39

What is parkinson's disease associated with?

Answer 39

The loss of dopaminergic neurones in the substantia nigra

Question 40

How can parkinsons be treated?

Answer 40

With L-DOPA (converted to dopamine by DOPA decarboxylase)

Question 41

What is a possible aeitology of schizopherenia? Back up with example

Answer 41

May be due to release of too much dopamine | - Amphetamines release dopamine and noradrenaline, which produces a schizophrnic like behaviour

Question 42

What do anti-psychotic drugs target?

Answer 42

Dopa,mine D2 receptors

Question 43

Where does noradrenaline in the brain come from?

Answer 43

Lcus ceruleus

Question 44

When are locus ceruleus active (and not)?

Answer 44

 Locus Ceruleus neurones inactive during sleep  Activity increases during behavioural arousal - Amphetamines increase release of noradrenaline and dopamine and increase waefulness

Question 45

What is the relationship between mood and state of arousal?

Answer 45

Depression may be associated with a deficiency of NA

Question 46

What are the functions of serotnin?

Answer 46

o Functions include sleep/wakefulness, mood, vomiting centre in brainstem

Question 47

What do SSRIs do?

Answer 47

o Selective Serotonin Reuptake Inhibitors (SSRIs) increase the concentration of serotonin in synapses, treating depression and anxiety