Neurones And Glia Flashcards
What are components of the cns
• Network of neurones with supporting glia
• Neurones sense changes and communicate with other neurones
– around 1011 neurones
• Glia support, nourish and insulate neurones and remove ‘waste’
– around 1012 glia
What are types of glial cells
• Astrocytes (several different types) – most abundant type of glial cell – Supporters • Oligodendrocytes – Insulators • Microglia – immune respons
What are the roles of astrocyted
• Structural support • Help to provide nutrition for neurones – glucose-lactateshuttle • Remove neurotransmitters (uptake) – control concentration of neurotransmitters (especially important for glutamate (toxic) • Maintain ionic environment – K+ buffering • HELP to form blood brain barrier
Hwo do astrocytes provide energy for neurones
• Neurones do not store or
•produce glycogen
Astrocytes produce lactate which can be transferred to neurones
• Supplements their supply of glucose
• Glucose lactate shuttle
Lactate used to produce atp
Glycogen can be stored in astrocytes. Can produce pyruvate, lactate. Transporters can transport lactate
Intense neuronal activity - need some more energy (atp) can get lactose lactate shuttel
Can operate for 10-15 min
How do astrocytes help to remove neurotransmitters
• Re-uptake
– Astrocyteshave transporters for transmitters such as glutamate
– Helps to keep the extracellular concentration low.
How do astrocytes help to buffer k+ in brain ecf
• High levels of neuronal activity could lead to a rise in [K+] in brain ECF
• Astrocytes take up K+ to prevent this
Can get build up of K= in ecf. If it gets too high will depot the surrounding Europe’s - spontaneous electrical activity - too much glutamate - toxic.
Astrocytes perm to cl-, keep memb potential very negative, so they can take upk+ - inward movement of k+ though channels and transporters - work to keep a low k+ conc
Astrocytes can be coupled. So k+ moves between them to maintain low
What are oligodendrocytes
- Responsible for myelinating axons in CNS
- Compare with PNS where Schwann cells are responsible for myelination
- Good time to revise ICPP Unit and myelination
What are microglia
• Immunocompetent cells • Recognise foreign material - activated • Phagocytosis to remove debris and foreign material • Brain’s main defence system Processes get wides when activated Mesodermal. Other glia are ectodermal a
What is the bbb
• Limits diffusion of substances from the blood to the brain extracellular fluid
• Maintains the correct environment for neurones
• Brain capillaries have
– tight junctions between endothelial cells
– basement membrane surrounding capillary
– end feet of astrocyte processes
Blood is not a suitable environment for neurones as it can have changing levels of, e.g. aas, k+, etc
Endothelial cells from tight junctions- prevents charge molecules difficusing into the brain extracellular space. (Astrocytes do not form bbb but associate)
Describe the pathways across the bbb
- Substances such as glucose and amino acids and potassium are transported across BBB.
- This allows the concentration to be controlled
Ions or small molecules rely on transporters and channels. Eg glucose in glut1. AAs are transported across - controlwhat crosses over into the brain ecf.
How is the brain immune specialised
• Does not undergo rapid rejection of allografts
• Rigid skull will not tolerate volume expansion
– Too much inflammatory response would be harmful - pressure
• Microglia can act as antigen presenting cells
• T-cells can enter the CNS
• CNS inhibits the initiation of the pro-inflammatory T-cell response
• Immune privilege is not immune isolation, rather specialisation
Descrbe neurotransmitter release at the synapse
- 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
Descrbe the postsynaptic response
• The response depends on – nature of transmitter
– nature of receptor
• Ligand-gated ion channels
• G-protein-coupled receptors
What are the 3 chemical classes of neurotransmitters
AMINO ACIDS
glutamate, GABA, glycine
BIOGENIC AMINES
acetylcholine, noradrenalin dopamine, serotonin (5-HT), histamine,
PEPTIDES
dynorphin, enkephalins, substance P, somatostatin cholecystokinin neuropeptide Y
Descrb amino aid neurotransmitters
• excitatory amino acids – mainly glutamate – major excitatory neurotransmitter • over 70% of all CNS synapses are glutamatergic • present throughout the CNS • inhibitory amino acids – GABA – Glycine
Desribe glutamate receptors
Ionotropic
AMPA Kainate NMDA
receptors receptors receptors Na+/K+ Na+/K+ Na+/K+
and Ca2+
Ion channel - permeable to Na+ and K+ (and in some cases Ca2+ ions)
Activation causes depolarisation – increased excitability
Metabotropic
mGluR1-7
G protein-coupled receptor
Linked to either:
• changes in IP3 and Ca2+ mobilisation
• or inhibition of adenylate cyclase and decreased cAMP levels
Describe teh response at glutamate receptors
Fast excitatory responses
• Excitatory neurotransmitters cause depolarisation of the postsynaptic cell by
acting on ligand-gated ion channels.
- excitatory postsynaptic potential (EPSP)
- depolarisation causes more action potentials
What are the fucntionsof different receptors at glutamierguc synapses
• Glutamatergic synapses have both AMPA and NMDA receptors
• AMPA receptors mediate the initial fast depolarisation
• NMDA receptors are permeable to Ca2+
• 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
Need ampa to depolarise to activate nomad.
Descrive glutamate receptors, synaptic plasticity and excitotoxicity
• 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 potentiation (LTP)
– Ca2+ entry through NMDA receptors important for induction of LTP
• Too much Ca2+ entry through NMDA receptors causes excitotoxicity – Too much glutamate - excitotoxicity
Lip underlies leaning and memory
Calcium going in - activate downstream signalling - more ampa - more depopulated
What are the main inhibitory amino acids
• GABA is the main inhibitory transmitter in the brain
GABA
• Glycine acts as an inhibitory neurotransmitter mostly in the brainstem and spinal cord
How do gaba and glycine receptors work
• GABAA and glycine receptors have integral Cl- channels
• Opening the Cl- channel causes hyperpolarisation
– Inhibitory post-synaptic potential (IPSP)
• Decreased action potential firing
How do barbiturates and benzodiazepines affect gaba receptors
- Barbiturates and benzodiazepines bind to GABAA receptors
- Both enhance the response to GABA - Both modulate the receptors to enhance the action city
– 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
– have sedative and anxiolytic effects
– used to treat anxiety, insomnia and epilepsy
Where s glycine in high conc
Brainstem ad spinal cord
What are bogenic amines and ach
- acetylcholine
- dopamine
- noradrenaline
- serotonin (5-HT)
- mostly act as neuromodulators • confined to specific pathways
Descrbe ach as a neurotransmitter
• ACh – neuromuscularjunction – ganglion synapse in ANS – postganglionic parasympathetic • ACh is 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
Wha are cholinergic pathways i the cns
- Neurones originate in basal forebrain and brainstem
- Give diffuse projections to many parts of cortex and hippocampus (longterm potentiation in hippocampus)
- There are also local cholinergic interneurones
- eg in corpus striatum
- Involved in arousal, learning & memory, motor control
- Degeneration of cholinergic neurones in the nucleus basalis is associated with Alzheimer’s disease
- Cholinesterase inhibitors are used to alleviate symptoms of Alzheimer’s disease
Describe dompanimeric pathways in the cns
Nigrostriatal pathway involved in movement control eg in Parkinson’s
Mesocortical pathwats - mood arousal and reward
Also tubero hypophyseal pathway
What are conditions associated with dopamine dysfunction
• Parkinson’s disease
– associated with loss of dopaminergic neurones
– substantia nigra input to corpus striatum
• Can be treated with levodopa - converted to dopamine by DOPA decarboxylase (AADC)
• Schizophrenia
• May be due to release of too much dopamine
– amphetamine releases dopamine & noradrenaline
– produces schizophrenic like behaviour
– antipsychotic drugs are antagonists at dopamine D2 receptors
– Other neurotransmitters also implicated
Descirb dopamine and the bbb
Ss
Describe NA as a neurotransmitter
- Noradrenaline - transmitter at postganglionic – effector synapse in ANS
- Also acts as a neurotransmitter in the CNS
- Operates through G protein-coupled α- and β-adrenoceptors
- Receptors to noradrenaline in the brain are the same as in the periphery
Describe Na pathways in the cns
Cell bodies of NA containing neurones are located in the brainstem (pons and medulla)
Diffuse release of NA throughout cortex, hypothalamus, amygdala and cerebellum
Desribe noradrenaline and behavioural arousal
• Most NA in the brain comes from a group of neurones in the locus ceruleus
– LC neurones inactive during sleep
– activity increases during behavioural arousal
– amphetamines increases release of noradrenaline and dopamine and increase wakefulness
• Relationship between mood and state of arousal
– depression may be associated with a deficiency of NA
Describe serotonergic pathways
Serotonin, 5-HT • Similar distribution to noradrenergic neurones FUNCTIONS • Sleep/wakefulness • Mood • SSRIs (serotonin selective reuptake inhibitors) treatment of depression and anxiety disorders
