Synapse independence breaks down during highly synchronous network activity in the rat hippocampus

Area of Science:

• Neuroscience
• Synaptic Plasticity
• Computational Neuroscience

Background:

• Hippocampal pyramidal cells (PCs) exhibit diverse firing patterns linked to behavior and network states.
• During theta rhythms, PCs fire asynchronously; during sharp waves, they fire synchronously at higher rates.

Purpose of the Study:

• To investigate how presynaptic activity of CA1 PCs influences their output synapse operation.
• To determine the impact of asynchronous versus synchronous PC firing on synaptic transmission.

Main Methods:

• Paired recordings to mimic single PC asynchronous firing.
• Extracellular stimulation of ~70 PC axons to emulate synchronous firing in acute hippocampal slices.
• Utilized low- and high-affinity glutamate receptor antagonists to analyze synaptic glutamate concentration transients.

Main Results:

• Synaptic transmitter concentration varied with release probability (P(r)) during synchronous activation.
• Increased P(r) during action potential trains slowed evoked excitatory postsynaptic current (EPSC) decay, indicating neurotransmitter spillover.
• This slowing was reversed by a low-affinity glutamate antagonist (gamma-D-glutamyl-glycine).
• Altering P(r) did not affect unitary EPSC kinetics.

Conclusions:

• Synapse independence is compromised during synchronous presynaptic activity.
• Asynchronous PC firing preserves point-to-point synaptic communication.
• Findings highlight the differential impact of firing patterns on hippocampal synaptic transmission.