Neurotransmitter Pathway Flashcards
What is a nuclei?
– Clusters of functionally related central neuronal cell bodies
• Cells forming nuclei may synthesize characteristic neurotransmitters
What are tracts?
– Bundled axons allowing communication between nuclei
• Tracts may mediate the release of specific neurotransmitters onto cells forming select target nuclei
Contract ACh receptors
Ionotropic: Nicotinic Change in ion flux (Na+, K+) Rapid Effects (milliseconds)
Metabotropic: Muscarinic Metabolic changes, e.g. phosphorylation Slower effects (seconds to minutes)
What is the pathology of Ahlzeimers to ACh?
Alzheimer’s disease
– Nucleus basalis of Meynert degenerates
– AChE inhibitor approved for treatment
• Not disease-modifying
Whaat do peripheral cholinergic neurons have in contact?
Somatic and preganglionic efferent fibers are myelinated
What is the function of cholinesterase?
Cholinesterase in synaptic cleft quickly degrades ACh, preventing desensitization and tetany
What is Myasthenia Gravis?
Myasthenia gravis
– Disrupted cholinergic transmission at neuromuscular junction
– Treatment
• AchE (esterase) inhibitors
What is SLUD?
– Salivation, lacrimation,
urination, defecation
• Overactivation of targets of the cholinergic postganglionic fibers
– Treatment
• Muscarinic receptor antagonists
– Atropine
Contrast the types of Glutamate receptors
Ionotropic glutamate receptors
• AMPA and Kainate receptors induce
Na/K flux after glutamate binding CAMKII
• EPSP summation unblocks the NMDA channel pore—> Ca2+ flux
Metabotropic glutamate receptors
Group1 mGLUR- (e) 1,5
Group 2 mGLUR- (i) 2,3
Group 3 mGLUR- (i) 4,6-8
What causes seizures?
– Heightened release of glutamate through hyper- synchronization of neuronal populations
– NMDA antagonists can be used to suppress seizures
– Reduced influx of calcium
How can glutamate defect oead to weakness?
– Reduced release of glutamate into bulbar and spinal motor nuclei
• As seen in Upper Motor Neuron Syndrome
Describe GABA nuclei and projections
GABAergic interneurons are ubiquitous
What are the GABAerguc pathways?
GABAergic pathways:
• Striatum -> substantia nigra
• Substantia nigra -> superior colliculus
and thalamus
• Medial vestibular
nuclei –> spinal
cord
• Cerebellar cortex ->
deep cerebellar nuclei
How can GABA be used to treat seizures?
Seizures
• Heightened release of glutamate through hyper-
synchronization of neuronal populations
- Treatment
- GABA agonists can inhibit hyper-excitable cells
How is GABA used to treat anxiety?
Mediated through altered excitability of limbic cells
• Treatment
• Benzodiazepines augment GABAergic transmission
• Reducing excitability
What are the nuclei and projections of the glycine?
Neurons tend to be small local inhibitiry interneurons
-Common in spinal and bulbar motor nuclei
Only one receptor type
Ionotropic with a Cl- channel
Blocked by strychnine
Describe synthesis and removal of glycine
Glycolysus of glucose yields. 3-phosphoglycerate, subsequently serine
Serine transhydroxymethylase folate-dependently converts serine to glycine
Membrane spanning transporters take up synaptic glycine
What is the mechanism of tetanus?
- Toxic protease suppresses release of glycine from bulbar and spinal interneurons
- Lower motor neurons are disinhibited
• Deploying muscle-relaxing strategies
directed at central or peripheral targets
What is the mechanism of Strychnine poisoning?
The alkaloid blocks glycine receptor on lower motor neurons, reducing chloride influx
• Lower motor neurons are disinhibited
In what cases can a cell synthesize NE but not E?
If a cell is DBH positive but PNMT negative, then it synthesizes NE but not E
What are the metabotropic Dopamine receptors?
All Metabotropic receptors:
D1-like – increases cAMP (D1/D5) D2-like – Decreases cAMP (D2-D4)
Reward, mood and movement
What are the dopamine based ailments?
Movement Disorders
Parkinsonism
• Decreased movement
• Treatment
• Dopamine agonists
Psychoses
• Hallucinations and delusions
• Treatment
• Dopamine antagonists(majortranquilizers)
What are the central projections of norepinephrine?
LC; Locus Coeruleus – diencephalon, limbic system (emotional centre), cerebral cortex (sensory pathways- micturition, cerebellum and spinal cord
What are the types of Norepinephrine receptors?
Metabotropic
• Alpha1/Beta1 GS
Alpha 1/Beta 1
• Excitatory
• Alpha2/Beta2
• Inhibitory
• Postganglionic PKA sympathetic
neurons excite cardiac musclHow is depression and pain treated?
- Treatment
- Norepinephrine agonists (re-uptake or MAO inhibitors) • Activates spinal and bulbar opioidergic neurons
* Suppresses release of substance P onto spinal dorsal horn and spinal trigeminal nucleus
- Norepinephrine agonists (re-uptake or MAO inhibitors) • Activates spinal and bulbar opioidergic neurons
How is Parkinsons treated?
• Sympathetic insufficiency
- Parkinson’s disease
- Orthostatic hypotension
- Loss of peripheral sympathetic neurons • Treatment
- Norepinephrine agonists
How is serotoninn pathways similar to noradrenergic pathways?
Noradrenergic pathways from Locus Coeruleus broadly similar – see previous slide
What is the frontal cortex impacted by serotonin?
-Social Context
-Appropriate
behaviours
How does serotonin impact the limbuc system?
- Emotions/mood
- Anxiety/Fear
How does serotoniimpact Ascending affecting system?
Arousal/wakeness
How does serotonin impact the spinal cord?
To spinal Cord, modulates
nociception and sexual reflexes
What are the types of serotonin receptors?
• Seven families 5-HT1 -5-HT7 and further subtypes, e.g. 5-HT1A
• All metabotropic with exception of 5-HT3 • 5-HT1, 5-HT5: inhibitory • 5-HT2: excitatory • 5-HT3: excitatory ionotropic (cation-permeable) • 5-HT4, 5-HT6, 5-HT7: excitatory
• Complex interactions of different 5-HT receptor isoforms can co- exist in the same neuron, e.g. spinal neurons governing micturition
How can serotonin be hsed to treat depression and pain?
Treatment
• Serotonin agonists (re-uptake or MAO inhibitors)
- Activates spinal and bulbar opioidergic neurons
- Suppresses release of substance P onto spinal dorsal horn and spinal trigeminal nucleus
