ALS is the most common motor neuron disease in humans, whereby upper and lower motor neurons degenerate. A major hypothesis underlying the mechanistic origin of neurodegeneration in ALS postulates that cortical hyperexcitability facilitates cell death. Previous research has identified the G4C2 hexanucleotide repeat expansion in the C9orf72 gene as the most common genetic cause of ALS; however, little is known about the contribution of the C9orf72 gene to neuronal excitability and synaptic dysfunction in the primary motor cortex. Thus, using C9orf72 knockout loss-of-function (C9-KO LOF) and gain-of-function (C9-GOF) mouse models, we assessed the intrinsic excitability of corticomotor neurons using whole-cell patch-clamp recordings made from acute brain slices. We have found that after disease onset, the action potential firing frequency is significantly lower in the C9-GOF mice compared to WT mice. Moreover, we have found a significant reduction in excitatory and inhibitory basal neurotransmission in the C9-GOF mice compared to WT mice. Finally, we have found significant alterations in pre-synaptic short-term plasticity and in the post-synaptic AMPA:NMDA ratio, suggesting both pre- and postsynaptic impairments in neurotransmission. In contrast, the C9-KO mice only exhibit a reduction in excitatory basal synaptic transmission, while intrinsic excitability and inhibitory transmission remain intact. Further investigation into the local circuitry will reveal essential information about the neurophysiological mechanisms underlying neurodegeneration in C9orf72 ALS patients.