Chunk #19 — 3. Overview of Monogenic Mouse Models of ASDs — 3.2 Post-Transcriptional Protein Modifiers or Regulators: Fmr1, Tsc1/2, Ube3a, and Pten — 3.2.1 Fmr1 (Fragile X syndrome)
In addition to dendritic spine morphology and stability, synaptic plasticity has been well characterized in FXS mouse models (reviewed in Chung et al., 2012; Sidorov et al., 2013). Initial studies reported no change in LTP (Godfraind et al., 1996; Paradee et al., 1999), but a significant enhancement in mGluR-dependent LTD in the hippocampus (Huber et al., 2002). More recently, impaired LTP was reported in hippocampal CA1 synapses using threshold-level stimulation parameters, which are thought to more closely mimic in vivo conditions (Lauterborn et al., 2007; Lee et al., 2011). Furthermore, a transient decrease (at postnatal day 14) in the AMPA/NMDA receptor ratio and an increase in NMDA-dependent LTP in hippocampal neurons has been observed (Pilpel et al., 2009). Reduced LTP has also been reported in somatosensory cortical synapses (Li et al., 2002), and increased mGluR-dependent LTD has been reported in cerebellar Purkinje cells (Koekkoek et al., 2005). Therefore, like spine morphology, electrophysiological consequences of Fmr1 knockout vary across brain regions and development, but increased mGluR-dependent LTD seems to be a relatively consistent finding.
