2.1 The role of neurones and glia Flashcards
What is the function of neurones?
Sense changes and communicate with other neurones
What is glia?
Supporting cells. They support, nourish and insulate neurones and remove ‘waste’.
What is there more of, neurones or glia?
More glia, 10^12 whereas neurones are 10^11
What are the different types of glial cells? Give a brief function of each
Astrocytes- support cells, most abundant
Oligodendrocytes- insulators
Microglia- immune cells
What is the role of astrocytes?
Structural support Help to provide nutrition for neurones Remove neurotransmitters Maintain ionic environment Help to form the blood brain barrier
How do astrocytes provide nutrition for neurones?
Glucose- lactate shuttle
What are the transporters involved in the glucose lactate shuttle and where are they?
GLUT1- between capillary wall and astrocyte membrane, the transfer of glucose to glycogen
GLUT3- Direct glucose absortion into neurone
MCT1- Astrocyte membrane, transports lactate out
MCT2- On neuron surface, takes up lactate
What is stored in the astrocyte and what does it become?
Gylcogen in small quantities and is converted to pyruvate and then to lactate
How is energy produced in the neuron?
Lactate to pyruvate
Why re astrocytes used for energy production? When is it used most?
Because neurones cannot store glycogen but even astrocytes can only store small amounts thus only provide 10-15 mins worth of energy
How do astrocytes help to remove neurotransmitters?
Astrocytes gave transporters for transmitters such as glutamate which helps to keep the extracellular concentration low.
Why is it important to re-uptake glutamate?
Allows a new excitatory potential to be formed
Too mich extracellular NT e.g. glutamate is toxic
Why is it important to buffer K?
High levels of neuronal activity leads to a rise in K conc in the brain ECF which would cause more depolarisations, thus hyperexcitable neurones.
How to astrocytes buffer K+?
Astrocytes have a very negative resting potential so allow an inward K movement without depolarising.
What are oligodendrocytes?
Responsible for myelinating axons in the CNS
What is the equiavalent of oligodendrocytes in the PNS?
Schwann cells
What is the function of microglia?
They are immunocompetent cells, the rains macrophages
They phagocytose to remove debris and foreign material such as plaques
What can microglia act like?
Antigen presenting cells or T cells
What are the functions of the blood brain barrier?
Limits diffusion of substances from blood to the brain extracellular fluid
Maintains the correct environment for neurones
What are some features of brain capillaries?
Tight junctions between endothelial cells
Basement membrane surrounding the capillary
What assists in the formation of tight junctions that make the BBB?
Astrocyte foot processes
What is the function of tight junctions across the BBB?
Allows greater control of ions and substances that can move in and out of the brain as it inhibits passive diffusion
Why is the brain being immune privileged important?
It is encased within a rigid skull thus would not be able to accommodate the rapid expansion as a result of an inflammatory response
Which cells are involved in the immune response of the brain?
Microglia that can act as antigen presenting cells
T cells can enter but pro inflammatory t cell response is inhibited
What are the main sections of a neuron?
Dendrites Cell spam Axon hillock Axon Temrinals
Describe neurotransmitter release
Action potential travels down the axon to the hillock
Towards the presynaptic terminal
The depolarisation triggers the opening of VGCC
Ca2+ enters the presynaptic cleft
Vesicles containing the NT fuse with the presynaptic membrane
Release of NT that diffuses across the cleft to bind to receptors on the postsynaptic membrane
What things does the postsynaptic response depend on?
Nature of the neurotransmitter
Nature of the receptor
What are the three chemical classes the NT can be split into?
Amino acids
Biogenic amines
Peptides
Give examples of amino acid NT
Glutamate, GABA, glycine
Give examples of biogenic amine NTs
Ach, NA, dpoamine, seratonin, histamine
Give examples of peptide NTs
enkephalins, substance P, cholecystokinin, neuropeptide Y
Which amino acid NTs are excitatory?
Mainly glutamate
Which amino acid NTs are inhibitory?
GABA
Glycine
What is glycine dependant on?
Calcium
What are the 2 glutamate receptor types?
Ionotropic and metabotropic
Describe Ionotropic glutamate receptors, what does activation lead to
Ion channels that are permeable to Na and K and in some cases Ca
Activation causes depolarisation
Give examples of ionotropic receptors
AMPA receptor- NA and K
Kainate receptors- Na and K
NMDA- Na, K and Ca
Which are the ionotropic receptors mostly found at synapses and what are they responsible for?
AMPA and NMDA which are responsible for fast excitatory responses
Describe metabotropic glutamate receptors
GPCR
Linked to either changes in IP3 and Ca2
Or inhibition of adenyl cyclase and decreased cAMP levels
Describe fast excitatory responses
Excitatory NT e.g. Glutamate causes depolarisation of the post synaptic cell by acting on ligand gates channels, the release of glutamate depolarises to a threshold level from where action potentials are propagated
You get a number of post synaptic potentials converging onto a neurones and summating and bringing the neurones to threshold to fire AP
What receptors do glutamatergic synapses have?
AMPA and NMDA
What do AMPA receptors do primarily?
Mediate the initial fast depolarisation
What is NMDA dependant on?
It needs glutamate to bind, as well as glycine or serine as co-agonoists but will only open if the cell is depolarised
Explain the relationship between AMPA and NMDA
NMDA receptors need the cell to be depolarised and for this the AMPA receptors need to have been activated first for depolarisation to occur
But NMDA activation can up regulate AMPA receptors
What ions is NMDA permeable to? What is the unique ion?
Na, K and Ca
Ca is unique
Which part of brain function of glutamate receptors have an important role in?
Learning and memory
What can the combined potentiation of NMDA and AMPA lead to?
Strong high frequency potentiation- long term potentiation (LTP)
Which ion is important for LTP?
Ca entry
What is the negative consequence of Ca2+ entry?
Too much depolarisation causes excitotoxicity
How does excess Ca entry via NMDA effect stroke patients?
Stroke–> damage to neurones–> glutamate entry–> depolarisation spreads to neighbouring cells –> they release more glutamate–> more NMDA activation–? increased cell death around the infarct due to increased glutamate and calcium toxicity
What is the main inhibitory NT in the brain?
GABA
What is the main inhibitory NT in the brainstem and spinal cord?
Glycine
What ion channels do both inhibitory receptors have?
Cl-
What is the effect of opening of the inhibitory channels?
Cl inward movement, makes the membrane potential more negative, so fewer action potentials are fired
Name 2 drugs that bind to GABA receptors and what effect do they have on GABA
Barbiturates
Benzodiazapines
Both enhance the response to GABA
What are the actions and uses and risks of Barbiturates?
Anxiolytic and sedative actions (not used anymore), sometimes used as anti-epileptic drugs
Risk of fatal overdose also dependance and tolerance
What are benzodiazepines used for and what are its effects?
Have sedative and anxiolytic effects
Used to treat anxiety, insomnia and epilepsy
Describe the role of glycine in the patellar reflex?
In the knee jerk there is contraction of the quads which is by excitatory synapse involving glutamate but also relaxation of the hamstrings which is by glycine
What is the role of other NTs other than glutamate, GABA or Glycine?
Have more of modulatory role or involved in discreet pathways
Where are some places Acc receptors are found?
Neuromuscular junction
Ganglion synapse in ANS
Postganglionic parasympathetic
What effect can glutamate have on other NT?
Can enhance e.g. enhances glutamate effect at presynaptic neurones
What receptor types can Ach act on and what general effect does it have?
On both nicotinic and muscarinic (parasymp) and has a mainly excitatory effect
Where do the neurones of cholinergic pathways originate?
Forebrain and brainstem
Where do the cholinergic pathway neurones diffuse to?
Give diffuse projections to manu parts of cortex and hippocampus
Which parts of the brain are included in the cholinergic pathways?
Septohippocampal pathway
Nucleus basalis
This includes Hippocampus, amygdala and hypothalamus
What is the cholinergic pathway involved in?
Arousal, learning, memory and motor control
What is the association of cholinergic pathways in alzheimers?
Degenration of cholinergic neurones in the nucleus basalis is associated with alzheimers disease
What is used to treat alzheimers?
Chominesterase inhibitors are used to alleviate the symptoms
Name the dopaminergic pathways in the CNS
Mesocortical pathways
Mesolimbic pathway
Nigrostriatal pathway
What are the dopaminergic pathways in the CNS involved in mood, arousal and reward?
Mesocortical and mesolithic pathways
What are the dopaminergic pathways in the CNS involved in motor control?
Nigrostriatal pathway
What are 2 conditions associated with dopamine dysfunction?
Parkinsons
Schizophrenia
What is parkinson’s associated with? Which parts of the brain?
Associated with loss of dopaminergic neurones in areas substantial nivea inout to the corpus striatum
What is the treatment for Parkinsons?
Levodopa which is converted to dopamine by DOPA decarboxylase
What is the reason for schizophrenia?
Maybe due to a release of too much dopamine, by amphetamine which releases excess dopamine and NA
What is the treatment for schizophrenia?
Antipsychotic drugs are antagonists at dopamine D2 receptors
Explain the method of action go L-DOPA
LDOPA is able to move into the through the BBB via LNAA where it is converted to dopamine via AADC
How is excess dopamine in the peripheries prevented?
Carbidopa inhibits AADC so doesn’t allow the breakdown to dopamine but is also not absorbed across the BBB
Where are the locations of noradrenaline?
At postganglionic effector synapse in AND as well as a NT in CNS
Where are cell bodies of noradrenergic pathways found?
Located in the brainstem (pons and medulla)
Where do the cell bodies of noradrenergic pathways diffuse to?
Diffuse release of NA throughout cortex, hypothalamus, amygdala and cerebellum
Where do most noradrenaline come from?
Most NA in the brain comes from a group of neurones in the locus ceruleas
When are the neurones of locus ceruleas active and inactive?
Inactive when sleeping
Active during behavioural arousal
Effects of amphetamines? what are the effects?
Increase the release of noradrenaline and dopamine and increase wakefulness
Which condition may be associated with a deficiency of NA?
Depression
There seems to be a relationship between mood and state of arousal
Describe the distribution of serotonin. What is it similar to?
Similar to that of dopamine
From the brainstem to the cerebral cortex, cerebellum, hippocampus and amygdala (raphe nuclei)
What are the functions of seratonin
Sleep/wakefullness
Mood
Any drugs associated with seratonergic pathways? What is it used for?
SSRIs used in the treatment go depression and anxiety disorders
