Synaptic reliability correlates with reduced susceptibility to synaptic potentiation by brain-derived neurotrophic...

Area of Science:

• Neuroscience
• Synaptic Plasticity
• Molecular Biology

Background:

• Brain-derived neurotrophic factor (BDNF) is crucial for synaptic plasticity in the hippocampus.
• BDNF enhances synaptic transmission by increasing neurotransmitter release.
• The impact of BDNF on synaptic potentiation may vary based on initial synaptic properties.

Purpose of the Study:

• To investigate how the initial state of glutamatergic synapses influences their modification by BDNF.
• To determine the relationship between synaptic strength, release probability, and BDNF-induced potentiation.
• To explore potential mechanisms underlying the differential effects of BDNF on hippocampal synapses.

Main Methods:

• Simultaneous perforated patch-clamp recordings from pairs and triplets of hippocampal neurons.
• Analysis of excitatory postsynaptic current (EPSC) amplitude, coefficient of variation (CV), and paired-pulse facilitation.
• Manipulation of release probability (Pr) using altered extracellular calcium and adenosine application.

Main Results:

• Synaptic potentiation by BDNF was greater at weaker synapses and reduced at stronger ones.
• BDNF-induced potentiation correlated with higher CV and lower paired-pulse facilitation, indicating higher susceptibility at low release probability (Pr) synapses.
• Reducing Pr in strong synapses did not restore BDNF potentiation, suggesting factors beyond Pr saturation are involved.

Conclusions:

• The efficacy of BDNF in potentiating hippocampal synapses is dependent on the synapse's initial strength and release probability.
• Synaptic maturation may confer intrinsic properties that limit BDNF responsiveness, independent of release probability saturation.
• Individual neurons can exhibit synaptic terminals with varying sensitivity to BDNF.