Impaired synaptic plasticity in RASopathies: a mini-review

Area of Science:

• Neuroscience
• Genetics
• Developmental Disorders

Background:

• Synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), is crucial for learning and memory.
• Impairments in synaptic plasticity are implicated in the pathophysiology of developmental disorders.
• RASopathies, a group of genetic disorders affecting the RAS pathway, frequently present with neurocognitive deficits linked to impaired synaptic plasticity.

Purpose of the Study:

• To review studies utilizing transcranial magnetic stimulation (TMS) to assess synaptic plasticity in patients with RASopathies.
• To understand the specific alterations in synaptic plasticity associated with different RASopathies.
• To explore potential therapeutic avenues for learning deficits in these conditions.

Main Methods:

• Review of existing research employing TMS.
• Non-invasive investigation of cortical plasticity in human subjects.
• Analysis of synaptic plasticity in patients diagnosed with Neurofibromatosis 1 (NF1), Noonan syndrome (NS), and Costello syndrome.

Main Results:

• Patients with NF1 and NS demonstrated reduced LTP-like synaptic plasticity.
• Costello syndrome patients exhibited increased LTP-like synaptic plasticity.
• Lovastatin treatment normalized impaired LTP-like plasticity and enhanced intracortical inhibition in NF1 patients.

Conclusions:

• TMS is a safe and effective tool for evaluating synaptic plasticity and intracortical inhibition in RASopathies.
• Distinct patterns of synaptic plasticity exist across different RASopathies.
• Further understanding of synaptic plasticity impairments may lead to novel therapeutic strategies for learning disabilities in RASopathies.