Session 2: Neurophysiology Flashcards
What are the roles of neurones and glia?
- There are a network of neurone with supporting glia
- Neurones sense changes and communicate with other neurones
- Glia support, nourish and insulate neurones and remove waste
What are the types of glial cells?
- Astrocytes
- Oligodendrocytes
- Microglia
What are the functions of astrocytes?
- Structural support
- Helps to provide nutrition for neurones via Glucose lactate shuttle. Astrocytes produce lactate to supplement neuronal supply of glucose.
- Remove neurotransmitters (uptake) to keep their extracellular concentration low. Especially important in control of concentration of glutamate which is neurotoxic
- Maintain ionic environment – K+ buffering by uptake during high levels neuronal activity which can lead to high ECF K+ concentration.
- Helps to form blood brain barrier
What are the functions of the oligodendrocytes?
- Insulators
- Responsible for myelinating axons in CNS. Compare with PNS where Schwaan cells are responsible for myelination
What are the functions of microglia?
- Immune response
- Immunocompetent cells
- Recognise foreign material – activated
- Phagocytosis to remove debris and foreign material
- Brain’s main defence system
What is the purpose of the blood brain barrier?
- Limits diffusion of substances from blood to the brain extracellular fluid
- Maintains the correct environment for neurone
- Substances such as glucose, potassium and amino acids are transported across the blood brain barrier. This allows concentration to be controlled.
What are the features of the brain capillaries?
Brain capillaries have
- Tight junctions between endothelial cells
- Basement membrane surrounding capillary
- End feet of astrocyte processes
Why is the brain described as immune privileged?
- Does not undergo rapid rejection of allografts
- Rigid skull will not tolerate volume expansion so too much inflammatory response would be harmful
- CNS inhibits the initiation of pro-inflammatory T-cells response
- Immune privileged but not Immune specialised
How do immune cells work in the CNS?
- Microglia can act as antigen presenting cells
- T cells can enter the CNS
What is the neuronal structure?
- Cell soma
- Dendrites
- Axon
- Terminals
How are nerutrnsmitters release across the synapse?
- Depolarisation in terminal opens voltage-gated Ca2+ channels. Ca2+ ions enter the terminal
- Ca2+ triggers vesicles to fuse and release transmitter
- Neurotransmitter diffuses across the synaptic cleft and bind to receptors on the post synaptic membrane
- Response depends on nature of transmitter and nature of receptor (Ligand gated ion channels and GPCR)
What are the types of neurotransmitters?
- Amino acids
- Biogenic amines
- Peptides
Which neurotransmitter molecules are amino acids?
Excitatory amino acids
-Glutamate
Inhibitory amino acids
- GABA
- Glycine
Which neurotransmitter molecules are biogenic amines?
- Acetylcholine
- Dopamine
- Noradrenaline
- Serotonin (5-HT)
Which neurotransmitter molecules are peptides?
- Dynorphin
- Enkephalins
- Substance P
- Somatostatin
- Cholecystokinin
- Neuropeptide Y
What is glutamate?
The major excitatory neurotransmitter and over 70% of all CNS synapses are glutamatergic. It is present throughout the CNS.
What are the ionotropic receptors?
- AMPA receptors
- Kainate receptors
- NMDA receptors
What is the functions of ionotropic receptors?
- Ionotropic receptors have an ion channels that is permeable to Na+ and K+.
- Activation causes depolarisation increasing excitability
What is the action of metabotropic receptors?
Metabotropic receptors are GPCR. They are linked to either:
- Changes in IP3 and Ca2+ mobilisation
- Inhibition of adenylate cyclase and decreased cAMP levels
Describe fast excitatory response.
- Excitatory neurotransmitters cease depolarisation of the post synaptic cell by acting on ligand-gated ion channels
- Excitatory post-synaptic potential (EPSP)
- Depolarisation causes more action potentials
What is the action at glutamatergic synapses?
- Have both AMPA and NMDA receptors
- AMPA receptor mediates the initial fast depolarisation
- NMDA receptors are permeable to Ca2+. They are normally blocked by magnesium
- NMDA receptors need glutamate to bind and the cell to be depolarised to allow ion flow through the channel. Also, glycine acts as a co-agonist
What is the role of glutamate receptors?
- Glutamate receptors have an important role in learning and memory
- Activation of NMDA receptors (and mGLuRs) can up-regulate AMPA receptors
- Strong, high frequency stimulation causes long term action potentiation
- Ca2+ entry through NMDA receptors unimportant for induction of LTP
What can too much glutamate cause?
- Can cause excitotoxcity
- This is due to too much Ca2+ entry through NMDA receptors
What is he action of GABA?
-Main inihibitory transmitter in the brain
What is the action of barbiturates and benzodiazepines?
o Barbiturates - enhance response to GABA
Anxiolytic and sedative actions but not used now due to risk of fatal overdose and also dependance and tolerance
Sometimes used an anti-epileptic drug
o Benzodiazepines – enhance response to GABA
Have sedative and anxiolytic effects
Have used to treat anxiety, insomnia and epilepsy
What is the action of glycine?
Mostly active as an inhibitory neurotransmitter in the brainstem and spinal cord
How do GABA and Glycine receptors work?
- Have integral CL- channels
- Opening the Cl- channel causes hyperpolarisation
- Inhibitory post-synaptic potential (IPSP) to decrease action potential firing
What is the action of acetylcholine as a neurotransmitter?
Acts in:
- Neuromuscular junction
- Ganglion synapse in ANS
- Post ganglionic parasympathetic
What is the central neurotransmitter role of acetylcholine?
- 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
Where does the cholinergic pathways originate?
- Originates in the basal forebrain and brainstem
- Gives diffuse projections to many parts of the cortex and hippocampus
- Also has interneurones
What is the role of cholinergic pathways?
- Arousal
- Learning
- Memory
- Motor control
Describes how cholinergic pathways are associated with Alzheimer’s disease?
- Degeneration of cholinergic neurones in the nucleus basalis
- Cholinesterase inhibitors are used to alleviate symptoms of Alzheimer’s disease
What are the dopamineegic pathways in the CNS?
- Nigostriatal pathway: Involved in motor control
- Mesolimbic and Mesocortical pathway: Involved in mood, arousal and reward
Describe the features of Parkinson’s disease?
- Associated with loss of dopaminergic neurones. Affect substantia nigra input to corpus striatum
- Can be treated with levodopa (converted to dopamine by DOPA decarboxylase (AADC). Doesn’t work in the peripheral as DOPA decarboxylase inhibitor used, which can’t cross the blood brain barrier, therefore it works in the brain)
Describe the features associated with schizophrenia?
- Thought to be due to release of too much dopamine
- Amphetamine release dopamine and noradrenaline and produces schizophrenic like behaviour
- Antipsychotic drugs are antagonist at dopamine D2 receptors
What are the uses of noradrenaline in the body?
- Transmitter at postganglionic at the effect synapse in ANS
- Acts as a neurotransmitter in the CNS
- Operate through G-protein coupled alpha and beta adrenoceptors
- Receptors to noradrenaline in the brain are the same as in the periphery
Where does noradrenaline originate from?
- Cell bodies of noradrenaline containing neurone are located in the brainstem (pons and medulla)
- Diffuse release of noradrenaline throughout the cortex, hypothalamus, amygdala and cerebellum
What are the functions of serotonin the body?
- Similar distribution to noradrenergic neurones
- Functions are sleep/wakefulness and mood
- Serotonin selective receptor inhibitor(SSRIs) are used in the treatment of depression and anxiety disorders
Where does noradrenaline originate from?
Most NA in the brain comes from a group of neurones in the locus ceruleus of the pons
- LC neurones inactive during sleep
- Activity increases during behavioural arousal
- Amphetamines increases release of noradrenaline and dopamine and increase wakefulness
How does noradrenaline affect behaviour?
- Relationship between mood and state of arousal
- Depression may be associated with a deficiency of NA
