National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560065, India.
Proc Natl Acad Sci U S A. 2011 Sep 6;108(36):E646-54. doi: 10.1073/pnas.1106411108. Epub 2011 Jul 27.
Despite its ubiquity and significance, behavioral habituation is poorly understood in terms of the underlying neural circuit mechanisms. Here, we present evidence that habituation arises from potentiation of inhibitory transmission within a circuit motif commonly repeated in the nervous system. In Drosophila, prior odorant exposure results in a selective reduction of response to this odorant. Both short-term (STH) and long-term (LTH) forms of olfactory habituation require function of the rutabaga-encoded adenylate cyclase in multiglomerular local interneurons (LNs) that mediate GABAergic inhibition in the antennal lobe; LTH additionally requires function of the cAMP response element-binding protein (CREB2) transcription factor in LNs. The odorant selectivity of STH and LTH is mirrored by requirement for NMDA receptors and GABA(A) receptors in odorant-selective, glomerulus-specific projection neurons(PNs). The need for the vesicular glutamate transporter in LNs indicates that a subset of these GABAergic neurons also releases glutamate. LTH is associated with a reduction of odorant-evoked calcium fluxes in PNs as well as growth of the respective odorant-responsive glomeruli. These cellular changes use similar mechanisms to those required for behavioral habituation. Taken together with the observation that enhancement of GABAergic transmission is sufficient to attenuate olfactory behavior, these data indicate that habituation arises from glomerulus-selective potentiation of inhibitory synapses in the antennal lobe. We suggest that similar circuit mechanisms may operate in other species and sensory systems.
尽管行为习惯化无处不在且意义重大，但就其潜在的神经回路机制而言，人们对此仍知之甚少。在这里，我们提供的证据表明，习惯化是由于在神经系统中普遍重复的电路模式中抑制性传递的增强而产生的。在果蝇中，先前的气味暴露会导致对这种气味的选择性反应减少。短期（STH）和长期（LTH）嗅觉习惯化都需要 rutabaga 编码的腺苷酸环化酶在多神经节局部中间神经元（LN）中的功能，这些 LN 介导了触角叶中的 GABA 能抑制；LTH 还需要 cAMP 反应元件结合蛋白（CREB2）转录因子在 LN 中的功能。STH 和 LTH 的气味选择性与 NMDA 受体和 GABA(A)受体在气味选择性、肾小球特异性投射神经元（PN）中的功能相匹配。LN 中需要囊泡谷氨酸转运蛋白表明，这些 GABA 能神经元中的一部分也释放谷氨酸。LTH 与 PN 中气味诱发的钙通量减少以及相应的气味反应性肾小球的生长有关。这些细胞变化使用与行为习惯化所需的类似机制。结合增强 GABA 能传递足以减弱嗅觉行为的观察结果，这些数据表明习惯化是由于触角叶中肾小球选择性抑制性突触的增强而产生的。我们认为，类似的电路机制可能在其他物种和感觉系统中起作用。
