Mutations of the neurofibromin gene (NF1) cause neurofibromatosis type 1 (NF1), a disease in which learning disabilities are common. Learning deficits also are observed in mice with a heterozygous mutation of Nf1 (Nf1 ^+/−). Dysregulation of regulated neurotransmitter release has been observed in Nf1 ^+/− mice. However, the role of presynaptic voltage-gated Ca²⁺ channels mediating this release has not been investigated. We investigated whether Ca²⁺ currents and transmitter release were affected by reduced neurofibromin in Nf1 ^+/− mice. Hippocampal Ca²⁺ current density was greater in neurons from Nf1 ^+/− mice and a greater fraction of Ca²⁺ currents was activated at less depolarized potentials. In addition, release of the excitatory neurotransmitter, glutamate, was increased in neuronal cortical cultures from Nf1 ^+/− mice. Dendritic complexity and axonal length were also increased in neurons Nf1 ^+/− mice compared to wild-type neurons, linking loss of neurofibromin to developmental changes in hippocampal axonal/cytoskeletal dynamics. Collectively, these results show that altered Ca²⁺ channel density and transmitter release, along with increased axonal growth may account for the abnormal nervous system functioning in NF1.