S2: the environment of the brain

Question 1

List different types of glial cells

Answer 1

Astrocytes – most abundant type of giant cell, supporters
Oligodendrocytes – insulators
Microglia – immune response

Question 2

List different roles of astrocytes

Answer 2

Structural support 
Help to provide nutrition for neurones 
Remove neurotransmitters 
Maintain ionic environment 
Help to form the BBB

Question 3

How do astrocytes help provide energy for neurones?

Answer 3

Neurones do not store or produce glycogen
Astrocytes produce lactate which can be transferred to neurones
-supplements their supply of glucose
-via the glucose lactate shuttle

Question 4

How do astrocytes help to remove neurotransmitters?

Answer 4

Astrocytes have transporters for transmitters such as glutamate
Re-uptake of transmitters, which helps to keep the extracellular concentration low

Question 5

Describe how astrocytes maintain the ionic environment

Answer 5

High levels of neuronal activity could lead to a rise in K+ in brain ECF
Astrocytes take up K+ to prevent this

Question 6

What is the role of oligodendrocytes?

Answer 6

Responsible for myelinating axons in CNS

(NB: in PNS, Schwann cells are responsible for myelination

Question 7

Describe the function of microglia

Answer 7

Immunocompetent cells
Recognise foreign material
Phagocytosis to remove debris and foreign material – brain’s main defence system

Question 8

Describe the blood brain barrier

Answer 8

Limits diffusion of substances from the blood to the brain ECF
Maintains the correct environment
Brain capillaries have: tight junctions between endothelial cells, basement membrane surrounding capillary & end feet of astrocyte processes

Question 9

Describe the ‘immune privilege’ of the CNS

Answer 9

Constant surveillance of the CNS by immune cells, however their activity is tightly regulated
Tight regulation is essential = strong inflammatory response in the brain would lead to swelling and hence raised ICP

Question 10

List the four main sections of a neurone

Answer 10

Cell soma
Dendrites
Axon
Terminals

Question 11

Describe neurotransmitter release from the synapse

Answer 11

Depolarisation in the terminal opens voltage-gated Ca2+ channels
Ca2+ ions enter the terminal
Vesicles fuse and release transmitter
Neurotransmitter diffuses across the synaptic cleft and binds to receptors on the postsynaptic membrane

Question 12

What does the postsynaptic response depend on?

Answer 12

Response depends on:

1) Nature of transmitter
2) Nature of receptor (ligand-gated or GPCR)

Question 13

Describe the three chemical classes of neurotransmitters

Answer 13

Amino acids – glutamate, GABA, glycine
Biogenic amines – acetylcholine, noradrenaline, dopamine, serotonin, histamine
Peptides – dynorphin, enkephalins, substance P, somatostatin, CCK, neuropeptide Y

Question 14

Describe amino acid neurotransmitters

Answer 14

Excitatory amino acids – mainly glutamate
-major excitatory neurotransmitter (over 70% of all CNS synapses are glutamatergic)
-present throughout the CNS
Inhibitory amino acids – GABA and glycine

Question 15

Describe ionotropic glutamate receptors

Answer 15

AMPA receptors – Na+/K+
Kainite receptors – Na+/K+
NMDA receptors – Na+/K+ and Ca2+
Ion channel – permeable to Na+ and K+ (and in some cases Ca2+ too)
Activation causes depolarisation – increased excitability

Question 16

Describe metabotropic glutamate receptors

Answer 16

mGluR1-7 (GPCR)
Linked to either:
- Changes in IP3 and Ca2+ mobilisation
- Or inhibition of adenylate cyclase and decreased cAMP levels

Question 17

Describe fast excitatory responses

Answer 17

Excitatory neurotransmitters cause depolarisation of the postsynaptic cell by acting on ligand-gated ion channels

• Excitatory postsynaptic potential
• Depolarisation causes more action potentials

Question 18

Describe glutamatergic synapses

Answer 18

Have both AMPA and NDMA receptors
AMPA receptors mediate the initial fast depolarisation
NDMA receptors are permeable to Ca2+
NDMA receptors need glutamate to bind and the cell to be depolarised to allow ion flow through the channel (glycine acts as a co-agonist)

Question 19

Describe the role of glutamate receptors in learning and memory

Answer 19

Activation of NMDA receptors can up-regulate AMPA receptors
Strong, high frequency stimulation causes long term potentiation (LTP)
Ca2+ entry through NMDA receptors important for induction of LTP
Too main Ca2+ entry through NMDA receptors causes excitotoxicity

Question 20

What is long term potentiation?

Answer 20

If the synapse is activated strongly and a lot of glutamate is released, then additional AMPA receptors are inserted into the postsynaptic membrane
Mediated by the entry of Ca2+ through NMDA receptors
Extra AMPA receptors means that the synapse will transmit more readily
This is the process of LTP – molecular basis for learning and memory

Question 21

Describe inhibitory amino acids

Answer 21

GABA – main inhibitory transmitter in the brain

Glycine – inhibitory neurotransmitter mostly in the brainstem and spinal cord

Question 22

Describe GABA and glycine receptors

Answer 22

GABA and glycine receptors have integral Cl- channels
Opening the Cl- channel causes hyperpolarisation
-inhibitory post-synaptic potential = decreased action potential

Question 23

Describe the action of barbiturates and benzodiazepines when they bind to GABA receptors

Answer 23

Barbiturates – anxiolytic and sedative actions, but not used for this now
-risk of fatal overdose, also dependence and tolerance
-sometimes used as anti-epileptic drugs
Benzodiazepines – sedative and anxiolytic effects
-used to treat anxiety, insomnia and epilepsy

Question 24

Describe acetylcholine as a neurotransmitter

Answer 24

ACh – neuromuscular junction, postganglionic parasympathetic in ANS
Also a central neurotransmitter – acts at both nicotinic and muscarinic receptors in the brain (mainly excitatory)
-receptors often present on presynaptic terminals to enhance the release of other transmitters

Question 25

Describe the cholinergic pathways in the CNS

Answer 25

Neurones originate in basal forebrain and brainstem
Give diffuse projections to many parts of cortex and hippocampus
Also local cholinergic interneurons (corpus striatum)
Involved in arousal, learning, memory and motor control
Cholinesterase inhibitors are used to alleviate symptoms of Alzheimer’s disease (degeneration of cholinergic neurones in the nucleus basalis are seen in this disease)

Question 26

Describe the key dopaminergic pathways

Answer 26

Nigrostriatal – motor control
Neocortical – mood, arousal and reward
Mesolimbic – mood, arousal and reward

Question 27

Describe conditions associated with dopamine dysfunction

Answer 27

Parkinson’s disease – associated with loss of dopaminergic neurones (substantia nigra input to corpus striatum)
Schizophrenia – may be due to release of too much dopamine (overactivity of mesolimbic pathway)
-amphetamine releases dopamine & noradrenaline -> produces schizophrenic like behaviour
-antipsychotic drugs are antagonists at D2 receptors

Question 28

Describe treatment for Parkinson’s

Answer 28

Commonly given drug is L-DOPA, converted to dopamine in the brain by the enzyme AADC
L-DOPA crosses the BBB readily via the LNAA
Problem: L-DOPA can also be converted to dopamine in periphery (causes side effects affecting the heart, GI and urinary systems)
Coadministration of carbidopa – inhibits the conversion in the periphery & doesn’t cross the BBB, hence action of L-DOPA in brain is unaffected

Question 29

Describe noradrenaline as a neurotransmitter

Answer 29

Transmitter at postganglionic – effector synapse in ANS
Also acts as a neurotransmitter in the CNS
Operates through GPCR alpha and beta-adrenoreceptors (receptors to NA in the brain are the same as in the periphery)

Question 30

Describe noradrenergic pathways in the CNS

Answer 30

Cell bodies of NA containing neurones are located in the brainstem (pons and medulla)
Diffuse release of NA throughout cortex, hypothalamus, amygdala and cerebellum

Question 31

Describe the relationship between noradrenaline and behaviour arousal

Answer 31

Most NA in the brain comes from a group of neurones in the locus coeruleus
-inactive during sleep
-activity increases during behaviour arousal
-amphetamines increases release of NA and dopamine and increase wakefulness
Depression may be associated with a deficiency of NA

Question 32

Describe serotonergic pathways in the CNS

Answer 32

Similar distribution to noradrenergic neurones
Functions: sleep/wakefulness, mood
SSRIs = treatment of depression and anxiety disorders