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Nat Commun ; 11(1): 6131, 2020 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-33257677


After a dorsal root crush injury, centrally-projecting sensory axons fail to regenerate across the dorsal root entry zone (DREZ) to extend into the spinal cord. We find that chemogenetic activation of adult dorsal root ganglion (DRG) neurons improves axon growth on an in vitro model of the inhibitory environment after injury. Moreover, repeated bouts of daily chemogenetic activation of adult DRG neurons for 12 weeks post-crush in vivo enhances axon regeneration across a chondroitinase-digested DREZ into spinal gray matter, where the regenerating axons form functional synapses and mediate behavioral recovery in a sensorimotor task. Neuronal activation-mediated axon extension is dependent upon changes in the status of tubulin post-translational modifications indicative of highly dynamic microtubules (as opposed to stable microtubules) within the distal axon, illuminating a novel mechanism underlying stimulation-mediated axon growth. We have identified an effective combinatory strategy to promote functionally-relevant axon regeneration of adult neurons into the CNS after injury.

Neuropsychopharmacology ; 43(12): 2350-2360, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29728645


The nucleus accumbens core (NAc) is important for integrating and providing information to downstream areas about the timing and value of anticipated reward. Although NAc is one of the first brain regions to be affected by drugs of abuse, we still do not know how neural correlates related to reward expectancy are affected by previous cocaine self-administration. To address this issue, we recorded from single neurons in the NAc of rats that had previously self-administered cocaine or sucrose (control). Neural recordings were then taken while rats performed an odor-guided decision-making task in which we independently manipulated value of expected reward by changing the delay to or size of reward across a series of trial blocks. We found that previous cocaine self-administration made rats more impulsive, biasing choice behavior toward more immediate reward. Further, compared to controls, cocaine-exposed rats showed significantly fewer neurons in the NAc that were responsive during odor cues and reward delivery, and in the reward-responsive neurons that remained, diminished directional and value encoding was observed. Lastly, we found that after cocaine exposure, reward-related firing during longer delays was reduced compared to controls. These results demonstrate that prior cocaine self-administration alters reward-expectancy encoding in NAc, which could contribute to poor decision making observed after chronic cocaine use.

Antecipação Psicológica/efeitos dos fármacos , Comportamento de Escolha/efeitos dos fármacos , Cocaína/administração & dosagem , Recompensa , Estriado Ventral/efeitos dos fármacos , Animais , Antecipação Psicológica/fisiologia , Comportamento de Escolha/fisiologia , Inibidores da Captação de Dopamina/administração & dosagem , Masculino , Distribuição Aleatória , Ratos , Ratos Long-Evans , Autoadministração , Estriado Ventral/fisiologia