Neural networks play a critical role in establishing constraints on excitability in the central nervous system. Several recent studies have suggested that network dysfunction in the brain and spinal cord are compromised following insult by a neurodegenerative trigger and might precede eventual neuronal loss and neurological impairment. Early intervention of network excitability and plasticity might therefore be critical in resetting hyperexcitability and preventing later neuronal damage. Here, the behavior of neurons that generate burst firing upon recovery from inhibitory input or intrinsic membrane hyperpolarization (rebound neurons) is examined in the context of neural networks that underlie rhythmic activity observed in areas of the brain and spinal cord that are vulnerable to neurodegeneration. In a non-inflammatory rodent model of spongiform neurodegenerative disease triggered by retrovirus infection of glia, rebound neurons are particularly vulnerable to neurodegeneration, likely due to an inherently low calcium buffering capacity. The dysfunction of rebound neurons translates into a dysfunction of rhythmic neural circuits, compromising normal neurological function and leading to eventual morbidity. Understanding how virus infection of glia can mediate dysfunction of rebound neurons, induce hyperexcitability and loss of rhythmic function, pathologic features observed in neurodegenerative disorders ranging from epilepsy to motor neuron disease, might therefore suggest a common pathway for early therapeutic intervention.