Synaptopodin is required for long-term depression at Schaffer collateral-CA1 synapses

Area of Science:

• Neuroscience
• Synaptic Plasticity
• Molecular Biology

Background:

• Synaptopodin (SP) is an actin-associated protein in telencephalic neurons influencing synaptic plasticity and dendritic spine dynamics.
• SP is known to be essential for metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD).
• The role of SP in other forms of LTD, such as low-frequency stimulation-induced LTD (LFS-LTD) and spike-timing dependent plasticity (STDP), remains largely unknown.

Purpose of the Study:

• To investigate the role of Synaptopodin (SP) in LFS-LTD and STDP at Schaffer collateral-CA1 (Sc-CA1) synapses.
• To determine the molecular mechanisms underlying SP's function in LTD, focusing on AMPA-receptor internalization and calcium signaling.
• To examine the impact of SP deficiency on long-term potentiation (LTP) at Sc-CA1 synapses.

Main Methods:

• Electrophysiology using ex vivo hippocampal slices from SP-deficient mice (SPKO) and wild-type littermates.
• Western blotting and immunochemistry to assess protein expression levels (e.g., AMPA receptors, IP3 receptors).
• Standard and modified stimulation protocols to induce LTD and LTP.

Main Results:

• SP deficiency in SPKO mice resulted in a significant deficit in LTD induction at Sc-CA1 synapses for both LFS-LTD and STDP.
• Western blotting and immunochemistry revealed reduced expression of AMPA receptors and IP3 receptors in SPKO mice.
• While LTD could not be induced in SPKO mice, long-term potentiation (LTP), though diminished, could be restored with a stronger stimulation protocol.
• No differences in N-methyl-D-aspartate receptor (NMDAR) expression were observed between SPKO and wild-type mice.

Conclusions:

• Synaptopodin (SP) is essential for the induction of activity-dependent LTD at Sc-CA1 synapses, particularly for LFS-LTD and STDP.
• The absence of SP leads to reduced expression of AMPA receptors and IP3 receptors, likely contributing to the LTD deficit.
• SP's role is specific to LTD induction, as LTP can still be induced, albeit with modified protocols, and NMDAR function remains intact.