- Describe the 4 criteria of a neurotransmitter
- what is the speed of transmission mediated by small molecule neurotransmitters?
- under what type of stimulation are small molecule neurotransmitters released?
- Describe how small molecule neurotransmitters are made
- Name 3 examples of small molecule neurotransmitters
- what type of vesicles store small molecule neurotransmitters?
- what is the speed of transmission mediated by neuropeptides?
- under what type of stimulation are neuropeptides released?
- Describe how neuropeptides are made
- Name 3 examples of neuropeptides
- what type of vesicles store neuropeptides?
- must be synthesised/present in presynaptic neuron
produce response in postsynaptic neuron
specific receptors for substance on postsynaptic neuron
must be a mechanism for removal
- low frequency and high frequency
- synthesising enzymes are made and packaged in ER and golgi, and transported down MTs to presynaptic terminal, where they synthesise and package neurotransmitters from precursors
- AcH. Biogenic Amines (DA, NA, 5-HT) and ATP
- small, clear core vesicles
- high frequency only
- neurotransmitter synthesised and packaged in ER and golgi and transported quickly down microtubules
- endorphins, angiotensin II and CCK
- large, dense vesicles
Describe the cycle of neurotransmitter release and inactivation/reuptake
- depolarisation phase of nerve impulse in presynaptic neuron activates CaV channels, leading to Ca influx
- increased [Ca] triggers exocytosis of synaptic vesicles, mediating neurotransmitter release into the synaptic cleft
- neurotransmitters diffuse across the synaptic cleft and bind to receptors on post synaptic terminal, mediating a response in the post synaptic cell
- Neurotransmitter can be removed in 3 ways:
- enzymatic degradation
- Name 3 processes that AcH is involved in
- How is AcH synthesised?
- Describe AcH break down and reuptake
- Name the two types of nicotinic receptors and where they are found
- Name the 5 types of muscarinic receptors and what their effects are.
- Learning and memory, sleep-wake cycles and thermoregulation
- synthesised from Choline (obtained from diet) and Acetyl CoA by cholinacetyltrandferase
- into Acetic acid and choline by acetylcholinesterase
Choline reuptake occurs via co-transport with sodium
- nicotinic N receptors - postganglionic neurons
nicotonic M receptors - skeletal muscle end plates
- M1, M3 and M5 are coupled to Gq - PLC
M2 and M4 are coupled to Gi - K channel opening
- what is the effect of glutamate on the post-synaptic neuron?
- what are high extracellular concentrations of glutamate linked to?
- how is glutamate synthesised?
- describe glutamate reuptake
- Name the 3 glutamate receptors
- Which receptors need a co-agonist and how?
- glutamate toxicity - many brain pathologies such as MND and epilepsy
- synthesised from glutamine by glutaminase
- removed by glutamate receptors located on pre-synaptic terminal and glial cells. Reuptake involves antiport with H+
in glial cells, glutamate is converted to glutamine, which is taken up by presynaptic neurons and converted back to glutamate
- AMPA, NMDA and kainate
glutamate binding to AMPA causes some depolarisation, which removes Mg block on NMDA
- what is the effect of GABA on the post-synaptic neuron?
- how is GABA synthesised?
- How is GABA removed?
- glutamate is converted to GABA by glutamic acid decarboxylase.
- transporters on the presynaptic terminal and glial cells remove GABA from the synaptic cleft
- what is the effect of glycine on the pre-synaptic neuron and where does it act?
- what type of receptors respond to Glycine?
- what are inherited defects in the glycine receptor associated with?
- Describe the role of Glycine in spinal cord reflexes
- major inhibitory neuron of the spinal cord
- ligand gated Cl channels
- glutamatergic upper MNs act on cholinergic lower motor neurons. Spinal cord interneurons called RENSHAW CELLS use glycine. They receive excitatory stimulation from alpha neurons, and inhibit the alpha motor neuron as part of negative feedback.
- Name the 4 biogenic amines
- describe the process of how these neurotransmitters are made
- how are these neurotransmitters inactivated?
- catecholamines - dopamine, noradrenaline and adrenaline
- synthesised from tyrosine
tyrosine >(tyrosine hydroxylase)> L-DOPA >(dopa decarboxylase)> dopamine > noradrenaline > adrenaline
- uptake by neuronal and extraneuronal tissues or enzymatic breakdown by MAO enzymes, or diffusion away from synaptic cleft
- MAO-A preferentially oxidises serotonin and noradrenaline
- MAO-B preferentially oxidises dopamine
- how is serotonin synthesised?
- describe the roles of serotonin (3)
- Describe serotonin synthesis and reuptake
- from tryptophan which is obtained from diet
- mood, emotional behaviour and sleep
- stored in synaptic vesicles by VMAT. reuptake into presynaptic neuron is mediated by SERT
- How is dopamine produced?
- name the 4 dopaminergic pathways in the brain and their roles
- which G proteins are the dopamine receptors coupled to?
- how is noradrenaline synthesised?
- where are NA neurons found in the brain?
- what are the roles of NA in the brain? (3)
- from L-DOPA by dopa-decarboxylase
- mesolimbic - reward pathway
nigrostriatal - initiation of movement
mesocortical - planning
tubero-infundibular- hypothalamus to pituitary gland. Inhibits release of prolactin
- D1 - Gs
D2 - Gi
- from Dopamine by dopamine beta hydroxylase
- locus coerulus
- sleep-wake cycle, attention and feeding behaviour.
- what is the input into the ANS? Give examples
- What is the role of autonomic motor neurons?
- Where are the cell bodies and axons of the following?
a) preganglionic neurons
b) postganglionic neurons
- autonomic motor neurons associated with interoceptors such as chemoreceptors and mechanoreceptors
- regulate visceral activities by increasing or decreasing ongoing activities in effector tissues
3a) cell bodies in spinal cord. Myelinated axon projects to automatic ganglion
3b) cell bodies in automatic ganglion. Unmyelinated axon projects to effector.
- What is the outflow of the sympathetic nervous system?
- what are sympathetic trunk ganglia?
- what type of viscera do sympathetic trunk ganglia innervate?
- What are paravertebral ganglia? Name the 3 types
- what do the paravertebral ganglia innervate?
- Describe the path that preganglionic neurons of the synpathetic trunk take to leave the spinal cord/ganglia
- Describe the path that paravertebral axons take
- What are chromaffin cells?
- ganglia that lie in a chain either side of the vertebral collumn.
- viscera above the diaphragm
- ganglia that lie away from the vertebral column and close to the large abdominal arteries. Celiac, superior mesenteric and inferior mesenteric
- viscera below the diaphragm
- leave spinal cord along with somatic motor neurons. Pass into anterior root of spinal nerve and enter the white ramus to pass into the nearest sympathetic trunk ganglion
leave sympathetic trunk by entering the grey ramus and merge with anterior ramus of spinal nerve
- pass through sympathetic trunk to outlying paravertebral ganglia known as splanchnic nerves.
- Cells in the adrenal medulla that secrete adrenaline and noradrenaline. There is no post-ganglionic neuron.
- What neurotransmitters do sympathetic neurons use?
a) preganglionic neurons
b) post ganglionic neurons
- How does sympathetic innervation of sweat glands differ?
- How do these neurotransmitters act on receptors?
- Describe the affinity of these neurotransmitters for their receptors
1a) AcH acting on nAcHr
2. Postganglionic neurons release AcH which acts on mAcHr
- activation of alpha1 and beta1 receptors causes excitation
activation of alpha2 and beta2 receptors causes inhibition
- Noradrenaline binds to alpha receptors more strongly than beta receptors
adrenaline has equal affinity for both receptors.
- what is the outflow of parasympathetic nerves?
- Where do preganglionic neurons emerge from?
- How do they leave the spinal cord?
- Where are autonomic ganglion found?
- what are pelvic splanchnic nerves and what do they innervate?
- What carries most of the parasympathetic output?
- What neurotransmitters do parasympathetic neurons use?
- cranial nerves - III, VII, IX and X
- emerge as part of cranial nerves or branches of saccral spinal nerves called pelvic splanchnic nerves
- near to or in effector tissues
- branches of saccral spinal nerves. Innervate pelvic viscera
- Vagus Nerve
7a) AcH acting on nAcHr
7b) AcH acting on mAcHr
- What is required for us to remain continent of urine?
- describe the sympathetic innervation of the bladder
- describe the parasympatheitc innervation of the bladder
- relaxation of bladder wall and contraction of urinary sphincter
- inhibits bladder wall (causing relaxation)
excites sphincter (causing contraction)
inhibits parasympathetic ganglion
- excites bladder wall (causing contraction)
- what is the effect of alpha adrenoreceptors?
2. what is the effect of beta adrenoreceptors?
- Vasoconstriction and decreased GI motlility
2. Bronchodilation and Increased Cardiac Output
PHARMACOLOGY OF THE PARASYMPATHETIC SYSTEM
What is the effects of the following drugs?
2. aminoglycoside antibioitcs
3. Botulinum toxin
- Neostigmine, physostigmine, pyridostigmine
- Carbacol, Pilocarpine and Hycosine
- blocks choline uptake into cells therefore limits AcH synthesis
- prevents AcH release
- prevents AcH release
- short acting cholinesterase inhibitor
- medium acting cholinesterase inhibitor
* bradycardia, hypotension, excessive secretion, bronchoconstriction and GI hypermotility - ENHANCE PARASYMPATHETIC STIMULATION
- nicotinic agonist.
- competitive nicotonic antagonists.
Cause hypotension, tachicardia, muscle paraylysis
- muscarinic agonist. Cause secretion, GI hypermotility and cardiac slowing
- muscarinic antagonist. causes tachicardia, decreased secretions, relaxation of smooth muscle.
PHARMACOLOGY OF THE SYMPATHETIC SYSTEM
- Tricyclic Antidepressants
- MAO inhibitors
- potentiates release of NA
- indirectly inhibit monoamine transporter function
- prevent reuptake of NA (and 5-HT)
- inhibits Monoamine reuptake
- inhibits breakdown of monoamines. Cheese effect due to lack of tyramine break down
- Alpha1 agonist - smooth muscle contraction
- beta2 agonist - bronchodilation
- Alpha2 agonist - antihypertensive
- Non selective alpha antagonist. decrease in BP
- Alpha1 antagonist - anti-hypertensive
- non selective beta blocker - reduce heart rate
- Beta1 antagonist - reduce heart rate