Development regulates a switch between post- and presynaptic strengthening in response to activity deprivation

Area of Science:

• Neuroscience
• Cellular Neuroscience
• Developmental Neuroscience

Background:

• Neurons exhibit compensatory increases in excitatory synaptic strength when activity decreases.
• The influence of neuronal maturity on these homeostatic plasticity mechanisms remains largely unexplored.

Purpose of the Study:

• To investigate how neuronal age affects the mechanisms of homeostatic synaptic plasticity.
• To compare the responses of young and mature cultured hippocampal neurons to activity deprivation.

Main Methods:

• Cultured hippocampal neurons were silenced using tetrodotoxin (TTX) at two developmental stages: 7 days in vitro (DIV) during synaptogenesis and 14 DIV after major synaptogenesis.
• Short (1 day) and longer (2 days) periods of silencing were applied.
• Presynaptic (neurotransmitter release probability, synaptic vesicle availability) and postsynaptic (glutamate receptor number) mechanisms were analyzed.

Main Results:

• After 1 day of silencing, young neurons (7 DIV) primarily used postsynaptic mechanisms, while mature neurons (14 DIV) relied on presynaptic mechanisms.
• Postsynaptic strengthening in young neurons was transcription-independent, whereas presynaptic strengthening was transcription-dependent.
• After 2 days of silencing, both young and mature neurons utilized both pre- and postsynaptic mechanisms.
• Additional mechanisms, including increased synapse number and dendritic electrotonic length, contributed to enhanced synaptic coupling after 2 days of silencing.

Conclusions:

• Neuronal maturity differentially regulates the expression of homeostatic synaptic plasticity mechanisms.
• The duration of activity deprivation also influences the recruitment of plasticity mechanisms.
• These findings provide insights into the developmental control of neuronal homeostasis.