3 - Glia

Question 1

What is the most abundant glial cell and what are it’s roles?

Answer 1

Astrocytes

• Structural support
• Nutrition
• Remove neurotransmitters
• Buffer
• BBB

Glial cells are smaller than neurons but are greater in number than nerve cells in the brain. Glial cells do not have axon and dendrites. However, they come into play during neural development or recovery from neural injury and during modulation of synaptic action and propagation of nerve signals.

Question 2

How do astrocytes provide nutrition to neurones?

Answer 2

Glucose-Lactate shuttle

Neurones cannot store or produce glycogen so astrocytes produce lactate from glucose for storage.

Lactate can be converted to to pyruvate when needed

Question 3

How do astrocytes remove neurotransmitters?

Answer 3

• Removes glutamate from synapses to prevent excitotoxicity
• Too much glutamate is toxic to cells due to increased Ca causing increased excitability

Question 4

How do astrocytes act as a buffer for the brain ECF?

Answer 4

• When neurones fire lots of A.Ps there is lots of K movement out of the cell

- Increase in K means neurones depolarise so inappropriate A.P firing so increased excitabilty

• Astrocytes have a slightly negative resting membrane potential so take up lots of potassium with chloride to stop this

Question 5

What is the role of oligodendrocytes?

Answer 5

Myelinate and insulate the neurones in the CNS

Antibodies attack these in MS

Question 6

What is the role of microglia?

Answer 6

Immunocompetent cells

• Become activated into phagocytes when they recognise foreign material
• Can antigen present to T cells

Question 7

What components make the BBB?

Answer 7

• Tight junctions between capillary endothelial cells
• Basement membrane around capillary
• End feet of astrocyte processes

Only substances like water, CO₂ and lipophilic substances can pass through easily

Question 8

How do substances get across the BBB?

Answer 8

• Substances like glucose, AA and potassium are all through transporters to allow ECF to be controlled

Question 9

Why is there a specialised immune response in the CNS?

Answer 9

• Normal inflammatory response would be harmful as skull prevents volume expansion
• T cells enter BBB and microglia antigen present to them.
• CNS inhibits the intiation of the proinflammatory T cell response

Question 10

How are neurotransmitters released from neurones?

Answer 10

• Depolarisation in the terminal opens VOCC so Ca enters
• Calcium causes vesicles with neurotransmitters to fuse with presynaptic membrane and released into cleft to bind with post synaptic membrane
• Response depends on what receptor it is, e.g GPCR or nAchR

Question 11

What are the different chemical classes of neurotransmitters?

Answer 11

• Amino acids
• Biogenic amines
• Peptides

Can be excitatory, inhibitory or modulatory

Question 12

What are the main excitatory and inhibitory amino acid neurotransmitters?

Answer 12

Excitatory: glutamate

Inhibitory: GABA and Glycine

Question 13

What are the different types of glutamate receptors?

Answer 13

• Metabotropic are GPCRs (same with GABA), these have a modulatory role

Question 14

How does a fast excitatory response occur?

Answer 14

- Glutamate causes depolarisation of post synaptic cell by acting on LGIC and causing a EPSP

- AMPA LGIC causes initial fast depolarisation as they are linked to an Na/K channel to allow Na influx to depolarise

• When the cell has been depolarised NMDA LGIC are activated and they are linked to a Ca channel to allow Ca in, which is important for memory and learning

Question 15

How are NMDA receptors activated?

Answer 15

• Cell needs to be depolarised to move Mg from pores and glutamate also needs to be bound
• Glycine can act as co-agonist

Question 16

How are NMDA receptors involved in learning and memory?

Answer 16

• Low levels of glutamate activates AMPA receptors which depolarise the cell and activate NMDA receptors
• Movement of Ca through NMDA induced long term potentiation and upregulation of AMPA receptors so cells are more sensitive to glutamate

ncluding long-term potentiation and long-term depression, which are important cellular correlates for learning and memory function …

Question 17

How is excitoxicity caused? How could dead cells cause this?

Answer 17

• Too much glutamate, lots of calcium uptake through NMDA so toxic
• e.g when patients have a stroke their glutamate levels can be toxic as dead cells release potassium which causes depolarisation and activation of NMDA so increasing Ca

The N-methyl-D-aspartate (NMDA) receptor is a receptor of glutamate, the primary excitatory neurotransmitter in the human brain.

Question 18

How do GABA and glycine act as inhibitory neurotransmitters?

And where specifically?

Answer 18

• GABA mainly in brain, glycine mainly in brainstem and spinal cord
• Receptors have integral Cl- channels so causes hyperpolarisation and IPSP so decreased AP firing

Question 19

How do barbiturates and benzodiazepines work as drugs?

What are they used to treat?

Answer 19

• Bind to GABA receptors to enhance the response to GABA to decrease neuronal activity
• Barbiturates: anti-epileptic drugs and previously sedative/anxiolytic. Risk of fatal OD and dependence

- Benzodiazepenes: treat anxiety, insomnia and epilepsy. have sedative and anxiolytic effect

Question 20

What neurotransmitter is involved in reflexes? Example?

Answer 20

• Glycine at inhibitory interneurones
• e.g released on patella reflex to relax hamstrings

Question 21

What are some neurotransmitters that act as neuromodulators?

Answer 21

Biogenic amines and Ach

Neuromodulators are substances that do not directly activate ion-channel receptors but that, acting together with neurotransmitters, enhance the excitatory or inhibitory responses of the receptors.

Question 22

Where does Ach act as a neurotransmitter?

Answer 22

• Neuromuscular junction (nAchR)
• Ganglion synapse in ANS
• Postganglionic parasympathetic (mAchR)

Mainly excitatory

Question 23

Where is most of the Ach in the CNS released?

Answer 23

• Nucelus Basalis releases Ach diffusely into the cortex and hippocampus
• Involved in arousal, memory and motor control

Question 24

How is the nucleus basalis related to Alzheimer’s?
Where is it in the first place?

Answer 24

• First neurones to die in Alzheimers are here so lack of Ach release leading to memory loss and loss of motor control

- Cholinesterase inhibitors used to help symptoms of Alzheimers as they stop Ach breakdown

Located in basal forebrain

Question 25

Where is most of the dopamine in the CNS released from?

Answer 25

Question 26

How is Parkinson's disease associated with dopamine dysfunction, and how can it be treated?

Answer 26

**- Nigrostriatal pathway** is the first to die so lack of dopamine to this area of the brain and lack of motor control - Give **levodopa**, which is converted to dopamine by DOPA decarboxylase (**AADC**) in the brain. Give with **carbidopa**

Question 27

How does Schizophrenia come about? And how do drugs solve this?

Answer 27

**- Too much dopamine release** - Antipsychotic drugs are **dopamine receptor antagonists** - Drugs like amphetamines can produce schizophreic like behaviour as they cause NA and dopamine release

Question 28

What is the role of noradrenaline in the CNS?

Answer 28

- Outside the CNS it acts at postganglionic sympathetic synapses - In CNS acts on **GPCR alpha and beta receptors** - Release from **locus cerelus** in the brainstem and diffuses through cortex, hypothalamus and cerebellum. **Modulates mood and arousal** as LC not active in sleep

Question 29

What are some conditions that can arise from dysfunction of noradrenaline release ?

Answer 29

**- Depression**: deficiency of NA **- Amphetamines:** increase wakefulness due to the release of NA and dopamine. NA is involved in behavioural arousal

Question 30

What is the function of serotonin (5-HT)?

Answer 30

- Helps with mood and sleep - SSRIs can be used to treat depression and anxiety (MAKE SURE YOU KNOW THE NUCLEI FOR ALL OF THE NEUROTRANSMITTERS PREVIOUSLY MENTIONED)

Question 31

What is a peduncle?

Answer 31

White matter connecting a hemisphere to the brainstem

Question 32

What is the cerebrum?

Answer 32

- Part of the forebrain - Forebrain = cerebrum and thalamus

Question 33

In the midbrain, which structure connects the cerebral hemispheres to the brainstem\>

Answer 33

Crus cerebri (cerebral peduncles)

Question 34

What is the role off the superior colliculi?

Answer 34

Feautures of the dorsal midbrain that deal with reflex actions to visual stimuli

Question 35

What side effects can be caused by administering L-Dopa in Parkinson's disease?

Answer 35

- Increased dopamine by conversion of L-Dopa by AADC can cause GI side effects - Give carbidopa to stop AADC in the peripheries

Question 36

Label the different parts of the midbrain, including their roles. (Mickey Mouse)

Answer 36

**- Ears**: cerebral peduncles (descending motor fibres) **- Eyes**: red nucleus (motor control, pigmented in life) **- Eyebrows:** substantia niagra (dark in life) **- Tears:** medial lemniscus (part of sensory system up to thalamus) **- Mouth:** cerebral aqueduct surrounded by periaqueductal grey matter **- Triangle nose with tendrals:** CNIII nucleus and EdingerWestphal with fibres of CNIII **- Double Chin:** superior colliculus (reflext visual actions. inferior colliculus would be auditory reflex)