Synaptogenesis] Flashcards
What word can be used to describe synapse formation
Competitive - not all nerves/axons make synapses - not all synapses persist
What is an example of a cell that is present before sensory innervation
Merkel cells - specialised epithelium overlaying free nerve endings forming Merkel discs
What are the morphological changes that occur in synaptogenesis
Growth cone turns into a pre-synapse
The post synapse develops specializations
What is interesting about the cat visual cortex in early infants
At around day 10 - number of synapses/neurons increase as this is when the kitten first opens its eyes
Shows the synapse requires sensory input in order to differentiate
How might the site availability for a synapse be restricted
Astrocytes may cover the length of the cell body - only some dendrites are free for synaptogenesis
How might post-synaptic cells be specialised for synapse formation
May have pre-prepared sites e.e cadherin/other adhesion molecules
How does the neuromuscular junction form
Initially - receptors are diffusely distributed across the muscle cell
Agrin (a secreted proteoglycan) is produced by motor axons and released from their terminals - These are thought to induce clustering of AchR on the surface of the cell directly below the incoming motor axon terminal
Expression of genes encoding AchR subunits increases at the location underlying the terminal - simultaneously these genes are suppressed in the remaining area of the cell
Newly synthesised receptors are then incorporated
All this creates localisation
What is the difference between the motor neurons innervating pectoral muscle and motor neurons innervating the cutaneous maximus and latissimus dorsi
Neurons innervating pectoral muscles develop monosynaptic connections whereas cutaneous maximus and lats receive polysynaptic input from interneurons
How is the difference in innervation between pecs and lats controlled
Controlled by GDNF secreted from the cutaneous maximus and latissimus dorsi which turns on the transcription factor Pea3 in the motor neurons
What happens when there is a loss of Pea3
Motor neurons innervating cutaneous maximus and latissimus dorsi have the dendritic morphology of pectoral muscle (monosynaptic) innervating motor neurons and incorrect proprioceptive connections
What happens when there is a lack of synaptic input causing a loss of target neurons and the neuron synthesis neurotrophins
Anterograde transport of the neurotrophins
Trophic support not only for the targets in the periphery but there are complex interacions going on in the CNS
What is the primary determinant for synaptic survival
Co-ordinated synaptic activity pre and post synaptically
How does altering activity lead to changes in NMJ survival
Initially - multiple motor neurons innervate a single muscle fibre
Changes - one motor neuron fires and causes the muscle fibre to contract
This causes trophin release that supports that neuron so it survives - others die
What induces receptor clustering
Ach receptor inducing activity (ARIA)
Released by motor neurons - increases AchR subunit mRNA - especially e subunit which replaces the y subunit in the mature receptor
What role does ARIA have in the CNS
Member of the neuregulin family
multiple members of the family found in the CNS
Can upregulate NMDA receptors in the developing cerebellum