Restoring the regenerative capacity of adult neurons after spinal cord injury has been an important challenge of the past decades. Unlike the peripheral branch of the nervous system, CNS axons fail to regenerate following injury. This inability has a two-fold origin, a neuron-extrinsic and -intrinsic one. The former has been well described in literature and is related to the inhibitory effect of the CNS environment on outgrowth of adult neurites. The latter has been attributed to the cellular makeup of adult neurons which is primed toward synaptic maturity and functionality, as opposed to regeneration. Studies have largely focused on improving one or the other, and rarely on the different states produced by the complex product of both environments. While the exact mechanisms remain to be elucidated, our preliminary data shows that increasing intracellular levels of cAMP overcame the constraints of an inhibitory environment in WT mice, but not in mice lacking microtubule-associated proteins (MAP) namely MAP1B, pointing to the crucial role of MAP1B in the integration of extrinsic and intrinsic signals. In this context, the cAMP sensor EPAC was shown to be the effector underlying the regenerative properties of increased intracellular cAMP. Interestingly, MAP1B and EPAC putatively interact. Thus, using a well-established model of regeneration, namely cultured dorsal root ganglion neurons, we are investigating the role of MAP1B and EPAC in axonal regeneration through their modulation of vesicle trafficking and autophagy, phenomena that have been positively correlated with neurite outgrowth, leading to potential therapeutic strategies in treating spinal cord injury.