CNS Physiology and Transmission Flashcards
Describe the structure of a neurone
Dendrites - Have a number of receptors to receive input
Neurotransmitter - Determines types of neurone
Cell Body - ‘Factory’, production of proteins, neurotransmitters etc
Axon - Conducts action potential, insulated by myelin sheath
What are regions of the brain made up of?
Collections of cells with similar functions
What occurs at the synapse?
Neurotransmitter released into synapse (conversion to chemical signal)
Acts on receptors on dendrites of other neurones to carry on signal
What is a neuronal circuit?
Made up of a number of different neuronal pathways
Describe the motor circuit in the basal ganglia
Dopamine released into striatum from nigrostriatal pathway
Activates GABA neurone which projects onto a glutamate neurone in the thalamus, glutamate neurone projects to cortex
Synapses onto another glutamate neurone which projects to muscle
What do CNS treatments often target?
Pathology of symptom rather than disease
How are neuronal pathways named?
First part is where cell body begins, second part is where axon terminates
What are GABA and glutamate?
Neurotransmitters
Glutamate = Excitatory
GABA = Inhibitory
“On/off” receptors
What are the four process involved in neurotransmission?
Synthesis of neurotransmitter
Storage of neurotransmitter
Release into synapse
Inactivation or reuptake
Using acetylcholine as an example, describe the four processes of neurotransmission
Synthesised from choline + acetyl CoA by choline acetyltransferase (in excess)
Stored in vesicles in presynaptic terminal
Release stimulated by influx of calcium ions - exocytosis
Inactivated by acetylcholinesterase in synapse, 40-50% of choline transported back into cell to resynthesise
How can drugs be developed to target a more specific dopamine pathway?
Dopamine is broken down in the synapse in some pathways and in others it is taken back into the synapse
Enzyme and transporter provide specific drug targets
Using acetylcholine as an example, how do auto receptors work?
Control synthesis and release of acetylcholine from acetylcholine in the synapse
ACh that is released activates autoreceptors to dampen further release
How are excitatory signals transmitted?
Cause conformational change in postsynaptic receptors to create a sodium ion channel
Influx of sodium ions causes initiation of action potential in postsynaptic neurone
How are inhibitory signals transmitted?
Cause conformational change in postsynaptic receptors to create a chloride ion channel
Influx of chloride ions makes neurone more negative so no action potential and no further neurotransmitter release
How do neuromuscular junctions cause muscle contraction?
Chemical synapse between neurone and skeletal muscle fibre - ACh neurotransmitter
Ligand-gated ion channels on skeletal muscle cell membrane allow influx of sodium
Voltage increase causes calcium channels to open, resulting in muscle contraction
What is Myasthenia Gravis and how is it treated?
Antibodies interfere with ACh receptors at neuromuscular junction causing movement disorders
Commonly seen in facial/eye muscles
Pyridostigmine prevents breakdown of ACh to improve muscle contraction and strength
How is dopamine synthesised?
L-tyrosine to L-dopa by tyrosine hydroxylase
L-dopa to Dopamine by dopa decarboxylase
What drug is commonly used to increase dopamine transmission and why?
L-dopa
Dopamine cannot cross BBB, L-dopa transported across by LAT1 and converted to dopamine in brain
What is the negative to increasing dopamine transmission?
Dopamine in all pathways is increased, leading to side effects
When does dopamine have an excitatory function?
Acts on D1 (D1 and D5) receptors
When does dopamine have an inhibitory function?
Acts on D2 (D2, D3 and D4) receptors
What are the four dopamine pathways and what do they control?
Nigrostriatal Pathway - Motor function
Mesolimbic Pathway - Reward/pleasure pathway
Mesocortical Pathway - Cognition/memory
Tuberoinfundibular Pathway - Prolactin release
Which symptom of dopamine pathways is always first to be treated?
Psychosis
How is the amount of brain tissue increased?
Sulci (grooves) and gyri (ridges)
What are white matter and grey matter? How are the arranged in the CNS?
White matter - Axons and oligodendrocytes
Grey matter - Cell bodies and dendrites
Brain: White matter surrounded by grey matter, spinal cord is opposite
Where are epidurals/lumbar punctures carried out and why?
Lower third of the spine
Contains individual neurones instead of spinal cord, less likely to cause nerve damage
Describe the structure of the meninges
Connective tissue
Outer layer - Dura mater
Middle layer - Arachnoid mater
Inner layer - Pia mater
What is meningitis and how is it treated?
Bacterial infection resulting in inflammation of the meninges
Diagnosed with rash glass test
Benzylpenicillin (or cefotaxime if allergic), continue treatment with cefotaxime once hospitalised
What is the subarachnoid space?
Between arachnoid mater and pia mater
Contains cerebrospinal fluid to bathe and protect the brain
Describe the composition and function of CSF
Where is it produced?
Shock absorber
Similar composition to plasma with less protein
Choroid plexus structures
How much CSF is produced daily and how much remains in the CNS?
400-500ml a day
About 150ml in CNS
How is a build up of CSF prevented?
CSF secreted into lateral ventricles from choroid plexus structures
Drain through lateral ventricle to third ventricle
Then into fourth ventricle through cerebral aqueduct
Then from fourth ventricle into spinal column through central canal or into subarachnoid space through foramen of magendie
Once CSF reaches top of brain it drains into superior sagittal sinus and into venous blood
What could be a cause of a build up of CSF and what could this cause?
Brain tumour pressing on aqueduct
Could result in hydrocephalus
Describe the structure of the brain-CSF barrier
Leaky layer of endothelial cells next to layer of ependymal cells locked together
MRP and P-gp present in ependymal cells to prevent passage through barrier
Tight regulation of ions and fluid
Describe the structure of the blood-brain barrier
What can pass through?
Specialised endothelial cells locked together, surrounded by pericytes and astrocytes
MRP1, 2, 4 and 5, BCRP and P-gp present in capillary membrane
Allows passage of glucose, nucleosides and amino acids
Insulin and transferrin can cross barrier through receptor-mediated endocytosis
Small, hydrophilic molecules can pass through
Give an example of a drug that is not a substrate for P-gp and can enter the brain - state its effect
Promethazine - Causes sedation
Give an example of a method of administration for chemotherapy drugs in the brain
Tumour mass removed surgically and wafer containing drug inserted into area
Wafer dissolves to release drug into affected area
When would intrathecal administration be used?
When drug cannot cross the BBB
Give an example of a drug which must NOT be administered intrathecally and what to do in the case of accidental administration
Vincristine - Potent neurotoxin
Aspirate CSF and irrigate with intrathecal infusion of plasma (binds vincristine)
