Figure 6. Summary diagram.

Loss of FMRP results in a delay in brain maturation, which is especially obvious in the first 2 postnatal weeks in mice, in line with the peak expression of FMRP in neocortex at P7 (Till et al., 2012). This might explain the observed delay in the maturation of neuronal structure (dendritic spines; overelaboration of axons) and function (e.g., reduced cortical LTP). In addition, FMRP directly regulates the expression of a number of channels, transporters and synaptic proteins that lead to either increased intrinsic excitability of neurons or to diminished inhibition. Eventually, these defects coincide in creating hyperexcitability at the circuit and network level, which leads to impairments in behavior (attention deficit/hyperactivity, anxiety, frequent awakening from sleep), sensory hypersensitivity seizures, or impaired learning and cognition.