Neurofibromatosis type 1 (NF1) is a genetic disorder caused by reduction or absence of neurofibromin due to mutations in the NF1 gene that result in multiple behavioral defects among other aberrant phenotypes. To directly assess the consequences of Nf1 deficiency on evoked neuronal activity, potentially underlying neuroplasticity defects, we utilized null mutations, point mutations, and RNA interference to manipulate Nf1 levels in Drosophila melanogaster. Our study focused on assessing the functional alterations in the giant fiber system, a well-established electrophysiological model to study synaptic transmission and habituation. Our findings reveal that the absence or reduction of NF1 leads to significant changes in the characteristics and habituation properties of the giant fiber system, indicating synaptic dysfunction and impaired neurotransmission. Nf1 attenuation or loss deficiency resulted in significant delay in the habituation rate, suggestive of Autistic Spectrum manifestations of the disease. We attempted to rescue this deficit pharmacologically and we report on the outcome of these experiments. Overall, our study provides valuable insights into the functional consequences of Nf1 deficiency and highlights its critical role in maintaining synaptic integrity and neurotransmission, as well as possible pharmacological ameliorative routes and therapeutic interventions for NF1 and related disorders.