The basal ganglia(BG) act as a cohesive functional unit that regulates motor function,habit formation,and reward/addictive behaviors. However,it is still not well understood how the BG maintains wakefulness and suppre...The basal ganglia(BG) act as a cohesive functional unit that regulates motor function,habit formation,and reward/addictive behaviors. However,it is still not well understood how the BG maintains wakefulness and suppresses sleep to achieve al these fundamental functions until genetical y engineered systems developed these years. Significant research efforts have recently been directed at developing genetic-molecular tools to achieve reversible and cell-type specific in vivo silencing or activation of neurons in behaving animals. Optogenetic tools can be used both to specifically activate or inhibit neurons of interest and identify functional synaptic connectivity between specific neuronal populations,both in vivo and in brain slices. Another recently developed system by Roth and colleagues permits the selective and ″remote″ manipulation(activation and silencing) of neuronal activity via all 3 major GPCR signaling pathways(G_i,G_s and G_q). These so-called ″ designer receptors exclusively activated by designer drugs″(DREADD) involve mutant GPCRs that do not respond to their endogenous ligands but are responsive to otherwise inert biological compounds. Recently,we demonstrated the essential roles and the neural pathways of the neurons expressing adenosine A_(2A) receptors or dopamine D_1 receptors in the BG for sleep-wake regulation using the genetically engineered systems including optogenetics and DREADD. We proposed a plausible model in which the caudate-putamen and the nucleus accumbens integrates behavioral processes with sleep/wakefulness through adenosine and dopamine receptors.展开更多
文摘The basal ganglia(BG) act as a cohesive functional unit that regulates motor function,habit formation,and reward/addictive behaviors. However,it is still not well understood how the BG maintains wakefulness and suppresses sleep to achieve al these fundamental functions until genetical y engineered systems developed these years. Significant research efforts have recently been directed at developing genetic-molecular tools to achieve reversible and cell-type specific in vivo silencing or activation of neurons in behaving animals. Optogenetic tools can be used both to specifically activate or inhibit neurons of interest and identify functional synaptic connectivity between specific neuronal populations,both in vivo and in brain slices. Another recently developed system by Roth and colleagues permits the selective and ″remote″ manipulation(activation and silencing) of neuronal activity via all 3 major GPCR signaling pathways(G_i,G_s and G_q). These so-called ″ designer receptors exclusively activated by designer drugs″(DREADD) involve mutant GPCRs that do not respond to their endogenous ligands but are responsive to otherwise inert biological compounds. Recently,we demonstrated the essential roles and the neural pathways of the neurons expressing adenosine A_(2A) receptors or dopamine D_1 receptors in the BG for sleep-wake regulation using the genetically engineered systems including optogenetics and DREADD. We proposed a plausible model in which the caudate-putamen and the nucleus accumbens integrates behavioral processes with sleep/wakefulness through adenosine and dopamine receptors.
