Dendritic, delayed, stochastic CaMKII activation in behavioural time scale plasticity.

Area of Science:

• Neuroscience
• Synaptic Plasticity
• Molecular Mechanisms

Background:

• Behavioural time scale plasticity (BTSP) is a non-Hebbian form of synaptic plasticity occurring over seconds.
• BTSP in hippocampal CA1 neurons is vital for place cell formation.
• The precise molecular mechanisms governing BTSP remain largely unknown.

Purpose of the Study:

• To investigate the molecular mechanisms underlying BTSP induction at the single dendritic spine level.
• To determine the role of Ca2+/calmodulin-dependent kinase II (CaMKII) activation in BTSP.
• To elucidate the temporal dynamics and signaling pathways involved in BTSP.

Main Methods:

• Induction of BTSP in single dendritic spines using two-photon glutamate uncaging and postsynaptic current injection.
• Utilizing an advanced CaMKII sensor to monitor kinase activation.
• Employing optogenetic techniques to inhibit CaMKII activity post-induction.
• Investigating the role of IP3-dependent intracellular Ca2+ release.

Main Results:

• BTSP could be induced in single dendritic spines with temporally separated pre- and postsynaptic activity.
• CaMKII activation was not detected during BTSP induction but occurred 10-100s later (DDSC).
• Dendritic, delayed, and stochastic CaMKII activation (DDSC) required both pre- and postsynaptic activity.
• Optogenetic inhibition of CaMKII post-induction blocked synaptic potentiation, confirming DDSC's essential role.
• IP3-dependent Ca2+ release facilitated both DDSC and BTSP.

Conclusions:

• CaMKII integrates presynaptic and postsynaptic signals over an extended time window (tens of seconds) during BTSP.
• DDSC, rather than immediate synapse-specific activation, serves as the instructive signal for BTSP.
• Intracellular Ca2+ release plays a critical role in facilitating BTSP and DDSC.