Pirri Jennifer K, Rayes Diego, Alkema Mark J
Department of Neurobiology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Department of Neurobiology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America; Instituto de Investigaciones Bioquímicas de Bahía Blanca, UNS-CONICET, Bahía Blanca, Argentina.
PLoS Biol. 2015 Sep 8;13(9):e1002238. doi: 10.1371/journal.pbio.1002238. eCollection 2015.
Behavioral output of neural networks depends on a delicate balance between excitatory and inhibitory synaptic connections. However, it is not known whether network formation and stability is constrained by the sign of synaptic connections between neurons within the network. Here we show that switching the sign of a synapse within a neural circuit can reverse the behavioral output. The inhibitory tyramine-gated chloride channel, LGC-55, induces head relaxation and inhibits forward locomotion during the Caenorhabditis elegans escape response. We switched the ion selectivity of an inhibitory LGC-55 anion channel to an excitatory LGC-55 cation channel. The engineered cation channel is properly trafficked in the native neural circuit and results in behavioral responses that are opposite to those produced by activation of the LGC-55 anion channel. Our findings indicate that switches in ion selectivity of ligand-gated ion channels (LGICs) do not affect network connectivity or stability and may provide an evolutionary and a synthetic mechanism to change behavior.
神经网络的行为输出取决于兴奋性和抑制性突触连接之间的微妙平衡。然而，尚不清楚网络的形成和稳定性是否受网络内神经元之间突触连接的符号所限制。在此，我们表明在神经回路内切换突触的符号可逆转行为输出。抑制性酪胺门控氯离子通道LGC-55，在线虫逃避反应期间诱导头部松弛并抑制向前运动。我们将抑制性LGC-55阴离子通道的离子选择性切换为兴奋性LGC-55阳离子通道。工程化的阳离子通道在天然神经回路中正确运输，并导致与LGC-55阴离子通道激活所产生的行为反应相反的行为反应。我们的研究结果表明，配体门控离子通道（LGICs）的离子选择性切换不会影响网络连通性或稳定性，并且可能提供一种进化和合成机制来改变行为。
