Session 2 - Lecture 1: Cellular Physiology of the Brain

Question 1

What is the general function of a CNS glial cell and name the different types?

Answer 1

Support, nourish and insulate neurones and remove waste.
Astrocytes (most abundant) = supporters
Oligodendrocytes = insulators
Microglia = immune response

Question 2

What are the specific roles for astrocytes?

Answer 2

Structural support, helps to provide nutrition for neurones via glucose-lactate shuttle, removes neurotransmitters to control their concentration within synapse (e.g. glutamate can be neurotoxic), maintains ionic environment (especially K+ buffering) and helps to form BBB.

Question 3

Why do astrocytes help provide energy for neurones, describe the pathways?

Answer 3

Neurones themselves cannot store or produce glycogen, astrocytes must produce lactate which they transfer to neurones via the glucose-lactate shuffle.
TRANSASTROCYTE PATHWAY = Glucose (blood) –> BBB endothelium (GLUT1) –> glycogen (astrocyte) –> lactate –> MCT1 –> MCT2 –> pyruvate (neurone)
OR
DIRECT PATHWAY = Glucose (blood) –> BBB endothelium (GLUT1) –> glucose (GLUT3, neurone)

Question 4

How do astrocytes aid with neurotransmitter re-uptake?

Answer 4

Astrocytes contain transporters for transmitters such as glutamate to help keep the extracellular concentration low.

Question 5

How do astrocytes help to buffer K+ in the brain extracellular fluid and why?

Answer 5

High neuronal levels can lead to K+ build up within the ECF which would lead to inappropriate AP firing, astrocytes act as buffers and take up K+ to prevent this (dependent on Cl- uptake as well).

Question 6

Describe the role of oligodendrocytes.

Answer 6

Responsible for the myelination of axons within the CNS, one oligodendrocyte can myelinated multiple axons. Therefore their role involves support and insulation of CNS axons.

Question 7

Describe the role of microglia within the CNS and why is this role important.

Answer 7

Microglia are immunocompetent cells that recognise foreign material and become activated when they do. Once activated, they phagocytose the foreign material to remove it. This is the brain’s main defence system.

Question 8

What are the main roles of the blood brain barrier?

Answer 8

Limits diffusion of substances from the blood to the brain ECF and maintains the correct environment for neurones.

Question 9

What makes up the main components of the blood brain barrier in terms of brain capillaries?

Answer 9

Tight junctions between endothelial cells
Basement membrane surrounding capillaries
End feet of astrocyte processes.

Question 10

What substances need to be transported across the BBB?

Answer 10

Glucose, amino acids and potassium.

Question 11

Why is the CNS ‘immune privileged’ and what does this mean?

Answer 11

If you transplant brain tissue into another specimen, it is not rejected. As the skull if rigid, it can cannot tolerate significant volume expansion and therefore too much inflammatory response would be harmful. The CNS inhibits the pro-inflammatory T-cell response.

Question 12

What are the four main sections of a neurone?

Answer 12

Cell soma, dendrites, axon and terminals.

Question 13

In what three classes can neurotransmitters be divided and name one example from each?

Answer 13

Amino acids = glutamate, GABA, glycine
Biogenic amines = Acetylcholine, noradrenaline, dopamine, serotonin
Peptides = substance P, somatostatin, CCK

Question 14

Give examples of excitatory and inhibitory amino acid neurotransmitters within the CNS.

Answer 14

Excitatory = mainly glutamate (70%)
Inhibitory = mainly GABA and glycine (mostly brainstem and spinal cord).

Question 15

Describe the different types of glutamate receptors and which ions pass through each.

Answer 15

Ionotropic (integral ion receptors) = AMPA(Na/K), Kainate (Na/K), NMDA (Na/K/Ca) receptors. Activation causes depolarisation and increased excitability.
Metabotropic = mGluR1-7, GPCR (linked to IP3 and Ca mobilisation or AC inhibition and reduced cAMP).

Question 16

What is an excitatory postsynaptic potential (EPSP)?

Answer 16

An EPSP is the change in membrane voltage of a postsynaptic cell following the influx of positively charged ions into a cell (typically Na+) as a result of the activation of ligand-sensitive channels by excitatory neurotransmitters.

Question 17

Which specific receptor within a glutamatergic synapse is responsible for mediating the initial fast depolarisation?

Answer 17

AMPA receptors.

Question 18

In terms of glutamatergic synapse, which single receptor would be present that would mean the synapse was classed as ‘silent’?

Answer 18

NMDA receptor only cells.

Question 19

What is required within a synapse for NMDA receptors to activate?

Answer 19

Depolarisation, usually via AMPA receptors, allows the positively charged Mg which usually blocks the channel of NMDA receptors, to be pushed out.

Question 20

Define long term potentiation (LTP).

Answer 20

LTP is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neurons.

Question 21

Give an example of LTP.

Answer 21

Activation of NMDA receptors can up-regulate AMPA receptors, Ca2+ entry through NMDA receptors is important for the induction of LTP.

Question 22

What are the possible adverse affects of LTP in terms of NMDA receptors.

Answer 22

Too much Ca2+ entry through NMDA receptors causes excitotoxicity.

Question 23

What co-factor is required to NMDA receptors to be activated and what is the consequence if too much is present?

Answer 23

Glutamate –> too much = excitotoxicity.

Question 24

What integral ion channel to both GABAa and glycine receptors have and what are the consequences of this?

Answer 24

Cl- channels –> open –> hyperpolarisation –> inhibitory postsynaptic potential and decreased AP firing.

Question 25

What is an inhibitory postsynaptic potential (IPSP)?

Answer 25

An IPSP is a kind of synaptic potential that makes a postsynaptic neurone less likely to generate an action potential.

Question 26

What drugs bind to GABAa receptors and what do they do?

Answer 26

Barbiturates (not used much anymore) and benzodiazepines, both enhance the response to GABA.

Question 27

What are the uses and effects of barbiturates?

Answer 27

Anxiolytic and sedative effects, sometimes used as an anti-epileptic drug. Risk of fatal overdose and dependence and tolerance.

Question 28

What are the uses and effects of benzodiazepines?

Answer 28

Sedative and anxiolytic effects, used to treat anxiety, insomnia and epilepsy.

Question 29

Give an example of glycine inhibiting neurotransmission?

Answer 29

Glycine is present in high concentration in the spinal cord and brainstem. Inhibitory interneurones in the spinal cord release glycine which can inhibit the antagonist muscle (hamstrings) of the knee jerk reflex.

Question 30

Where can ACh be released as a neurotransmitter?

Answer 30

Neuromuscular junction, ganglion synapse in ANS, postganglionic parasympathetic, acts on nicotinic and muscarinic receptors in the brain.
Receptors are usually present on presynaptic terminals of glutamatergic synapses to enhance the release of other transmitters.

Question 31

Is ACh mainly excitatory/inhibitory?

Answer 31

Mainly excitatory.

Question 32

Describe the cholinergic pathways in the CNS.

Answer 32

Neurones originate in the basal forebrain and brainstem.
Project to hippocampus, thalamus and cortex.
Local cholinergic interneurones present within the corpus striatum.

Question 33

What are the cholinergic pathways in the CNS responsible for?

Answer 33

Arousal, learning, memory and motor control.

Question 34

What can degeneration of the cholinergic neurones in the nucleus basalis lead to and what can be used to treat this condition?

Answer 34

Alzheimer’s disease. Cholineesterase inhibitors to prevent the degradation of ACh can be used to alleviate symptoms.

Question 35

What dopaminergic pathways are present within the CNS and what are they involved with?

Answer 35

Substantia niagra involved in the Nigrostriatal pathway = motor control.
Amygdala involved with the Mesolimbic pathway = mood, arousal and reward.
Hypothalamus and pituitary involved with the Mesocortical pathway = mood, arousal and reward.

Question 36

What condition is involved with the loss of dopaminergic neurones and what is the common treatment?

Answer 36

Parkinson’s disease. Can be treated with levodopa which is converted to dopamine via DOPA decarboxylase, cannot treat with dopamine as it cannot cross BBB.

Question 37

What condition is involved with excessive dopamine and what is the common treatment?

Answer 37

Schizophrenia. Amphetamine releases dopamine and noradrenaline –> schizophrenic like behaviour.
Antipsychotic drugs are antagonists at dopamine D2 receptors.

Question 38

Describe where noradrenaline acts.

Answer 38

Transmitter at postganglionic effector synapse in ANS.
Also acts as neurotransmitter in CNS
Operates through alpha and beta adrenoceptors.

Question 39

Describe the noradrenergic pathways within the CNS.

Answer 39

Cell bodies (reticular formation and locus ceruleus) located within the brainstem (pons and medulla). 
Diffuse release of NA throughout the cortex, hypothalamus, amygdala and cerebellum.

Question 40

What is the significance of the locus ceruleus in terms of sleep? What drug can affect this?

Answer 40

LC. neurones inactive during sleep, activity increases during behavioural arousal. Amphetamines increases release of noradrenaline and dopamine and increases wakefulness.

Question 41

Name a condition which can affect the relationship between mood and state of arousal and name a treatment.

Answer 41

Depression may be associated to a deficiency in NA.

Treatment = SSRIs treat depression and anxiety disorders.

Question 42

Describe the serotonergic pathways in the CNS.

Answer 42

Similar distribution to NA neurones.
Areas involved include, thalamus, hypothalamus, hippocampus, amygdala, corpus striatum and substantial niagra.
Function = sleep/wakefullness and mood.