Ultrastructural synaptic changes associated with neurofibromatosis type 1: a quantitative analysis of hippocampal region CA1 in a Nf1(+/-) mouse model.

Abstract

Neurofibromatosis type 1 (NF1) is one of the most frequently diagnosed autosomal dominant inherited disorders resulting in neurological dysfunction, including an assortment of learning disabilities and cognitive deficits. To elucidate the neural mechanisms underlying the disorder, we employed a mouse model (Nf1(+/-) ) to conduct a quantitative analysis of ultrastructural changes associated with the NF1 disorder. Using both serial light and electron microscopy, we examined reconstructions of the CA1 region of the hippocampus, which is known to play a central role in many of the dysfunctions associated with NF1. In general, the morphology of synapses in both the Nf1(+/-) and wild-type groups of animals were similar. No differences were observed in synapse per neuron density, pre- and postsynaptic areas, or lengths. However, concave synapses were found to show a lower degree of curvature in the Nf1(+/-) mutant than in the wild type. These results indicate that the synaptic ultrastructure of Nf1(+/-) mice appears relatively normal with the exception of the degree of synaptic curvature in concave synapses, adding further support to the importance of synaptic curvature in synaptic plasticity, learning, and memory.