How injury or neurodegenerative disease alter neural circuit function remains unclear. In this thesis, I explored how axotomy affects severed axons and adjacent uninjured 'bystander' neurons in a simple in vivo nerve preparation. Following axotomy, I observed rapid suppression of transport in all axons, whether uninjured or not, and decreased sensory signaling in intact bystander neurons. Unexpectedly, the axon death gene dsarm was required for early changes in bystander neuron cell biology, as were the voltage-gated calcium channel Cacophony (Cac) and MAP kinase signaling. Bystander neurons later recovered, while severed axons degenerated via dSarm/Axundead signaling, and independently of Cac/MAP kinase. Interestingly, suppression of bystander neuron function required Draper receptor and JNK/MMP-1 signaling in glia, indicating glial cells actively suppress bystander neurophysiology. This work identifies a new role for Cac/dSarm/MAPK signaling and glia in the broad suppression of neural circuit function after injury, and defines two genetically and temporally separable phases of dSarm signaling in the injured nervous system.