Spike Timing-Dependent Plasticity at Layer 2/3 Horizontal Connections Between Neighboring Columns During Synapse...

Area of Science:

• Neuroscience
• Synaptic Plasticity
• Developmental Neurobiology

Background:

• Spike-timing-dependent plasticity (STDP) with long-term potentiation (LTP) and long-term depression (LTD) is vital for map plasticity.
• Plasticity in layer 2/3 (L2/3) horizontal connections contributes to map plasticity, particularly spared whisker response potentiation.
• All-LTP STDP drives circuit formation at thalamocortical and L4-L2/3 synapses before the critical period.

Purpose of the Study:

• To investigate the mechanisms of all-LTP STDP at L2/3 horizontal connections during synapse formation before the critical period.
• To determine the role of NMDA-receptor (NMDA-R) and PKA signaling in different timing-dependent LTP induction pathways.

Main Methods:

• Electrophysiological recordings in the developing mouse barrel cortex.
• Pharmacological manipulation using APV (NMDA-R antagonist) and PKI 6-22 (PKA inhibitor).
• Induction of LTP-STDP using pre-post and post-pre spike timing protocols.

Main Results:

• L2/3 horizontal connections exhibit all-LTP STDP during axonal extension before the critical period.
• Pre-post induced LTP-STDP is NMDA-R and PKA dependent.
• Post-pre induced LTP-STDP is not NMDA-R dependent but is PKA dependent.
• PKA signaling is essential for all-LTP STDP at L2/3-L2/3 connections.

Conclusions:

• PKA signaling plays a significant role in all-LTP STDP during synaptic formation at L2/3-L2/3 connections.
• Distinct Ca2+ influx sources mediate LTP-STDP depending on spike timing.
• These findings highlight the importance of PKA in shaping developing neural circuits via synaptic plasticity.