RESUMO
Symptoms of neurological diseases emerge through the dysfunction of neural circuits whose diffuse and intertwined architectures pose serious challenges for delivering therapies. Deep brain stimulation (DBS) improves Parkinson's disease symptoms acutely but does not differentiate between neuronal circuits, and its effects decay rapidly if stimulation is discontinued. Recent findings suggest that optogenetic manipulation of distinct neuronal subpopulations in the external globus pallidus (GPe) provides long-lasting therapeutic effects in dopamine-depleted (DD) mice. We used synaptic differences to excite parvalbumin-expressing GPe neurons and inhibit lim-homeobox-6expressing GPe neurons simultaneously using brief bursts of electrical stimulation. In DD mice, circuit-inspired DBS provided long-lasting therapeutic benefits that far exceeded those induced by conventional DBS, extending several hours after stimulation. These results establish the feasibility of transforming knowledge of circuit architecture into translatable therapeutic approaches.
Assuntos
Estimulação Encefálica Profunda/métodos , Dopamina/deficiência , Globo Pálido/fisiopatologia , Neurônios/fisiologia , Doença de Parkinson/terapia , Estimulação Elétrica Nervosa Transcutânea/métodos , Animais , Modelos Animais de Doenças , Dopamina/genética , Feminino , Globo Pálido/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Optogenética , Doença de Parkinson/fisiopatologia , Núcleo Subtalâmico/citologia , Núcleo Subtalâmico/fisiopatologia , Sinapses/fisiologiaRESUMO
The subthalamic nucleus-globus pallidus network is a potential source of oscillations in Parkinson's disease, but the mechanism is unknown. In this issue of Neuron, Chu et al. (2015) present a cortically driven form of heterosynaptic plasticity that could promote oscillatory activity after dopamine depletion.