2. Cellular Physiology Of The Brain Flashcards
What are the general functions of the glial cells?
Support, nourish and insulate neurones and remove ‘waste’
What are the 3 main types of glial cells?
Astrocytes
Oligodendrocytes
Microglia
What is the role of astrocytes?
Structural support
(Most abundant type of glial cell)
Remove neurotransmitters
Help to provide nutrition for neurones - glucose-lactate shuttle
Maintain ionic environment - K+ buffering
Help to form blood brain barrier
What is the general role of oligodendrocytes?
Responsible for myelinating axons in CNS
What is the general role of microglia?
Immune response
- recognise foreign material and become activated
- phagocytosis to remove debris and foreign material
How can astrocytes provide energy to neurones when glucose levels are low?
Astrocytes store glycogen which can be converted to lactate
This is then shuttled across to neurones via MCT1 and MCT2
Lactate is then converted to pyruvate, which is used to release ATP
How can K+ move into astrocytes?
K+ channels
Na+/K+ ATPase transporter
Na+/K+/2Cl- transporter
What is the purpose of the blood brain barrier?
Limits diffusion of substances from the blood to the brain extracellular fluid
Maintains correct environment for neurones
What are the features of brain capillaries that form the blood brain barrier?
Tight junctions between endothelial cells
Basement membrane surrounding capillary
End feet of astrocyte processes
Which substances are transported across the BBB?
Glucose
Amino acids
Potassium
O2, CO2 and water can freely move across
Why is the brain immune privileged?
Rigid skull will not tolerate volume expansion
Too much inflammatory response would be harmful
What makes the brain immune privileged?
Microglia can act as antigen presenting cells
T cells can enter the CNS
CNS inhibits initiation of pro-inflammatory T cell response
Describe the process of neurotransmitter release at the synapse
Depolarisation in terminal opens voltage-gated Ca2+ channels, Ca2+ ions enter the terminal
Vesicles fuse with pre-synaptic membrane and release neurotransmitter
Neurotransmitter diffuses across the synaptic cleft and binds to receptors on the postsynaptic membrane
What does the postsynaptic response depend on?
Nature of transmitter
Nature of receptor - ligand-gated ion channels, G-protein-coupled receptors
What are the 3 chemical classes of neurotransmitters in the CNS?
Amino acids - glycine, GABA, glutamate
Biogenic amines - ACh, NA, dopamine, histamine
Peptides - cholecystokinin, somatostatin, dynorphin, enkephalins
Name an excitatory amino acid neurotransmitter
Glutamate
Name 2 inhibitory amino acid neurotransmitters
GABA - brain
Glycine - brainstem and spinal cord
What are the 2 groups of glutamate receptors?
Ionotropic - contain integral ion channel
Metabotropic - contain G protein-coupled receptor
What happens during fast excitatory responses?
Excitatory neurotransmitters caused polarisation of the postsynaptic cell by acting on ligand-gated ion channels
Depolarisation causes more action potentials
Which receptors do glutamatergic synapses have?
AMPA - mediate initial fast response
NMDA - permeable to Ca2+
What do glutamate receptors have an important role in?
Learning and memory
How do glutamate receptors have a role in learning and memory?
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
How do GABA and glycine receptors cause inhibitory effects?
Have integral Cl- channels
Opening the Cl- channel causes hyperpolarisation
Inhibitory postsynaptic potential
Decreased section potential firing
Which drugs bind to GABAa receptors?
Barbiturates - sometimes anti-epileptic drugs
Benzodiazepines - anxiety, insomnia, epilepsy
Both enhance the response to GABA
What are the roles of cholinergic pathways in CNS?
Arousal, learning and memory, motor control
What happens to cholinergic neurones in Alzheimer’s disease?
Degeneration of cholinergic neurones in nucleus basalis
What are dopaminergic pathways in the CNS involved in?
Mood, arousal, reward, motor control
Name 2 conditions associated with dopamine dysfunction
Parkinson’s disease
Schizophrenia
Where does most NA in brain come from?
Group of neurones in locus coeruleus
What are the functions of serotonergic pathways in CNS?
Sleep/wakefulness
Mood
What are SSRIs?
Serotonin selective reuptake inhibitors
Used in treatment of depression and anxiety disorders
Increases amount of serotonin around
