Recurrent cortical circuits implement concentration-invariant odor coding.
Recurrent cortical circuits implement concentration-invariant odor coding.
复制标题
复发性皮质回路实施浓度不变的气味编码。
DOI：
10.1126/science.aat6904
复制
发表时间：
2018-09-14
期刊：
影响因子：
--
通讯作者：
Franks KM
中科院分区：
文献类型：
--
作者：
Bolding KA;Franks KM
物体可以看起来非常稳定，尽管它们向我们的感官提供了经常变化无常的信号。例如，一只觅食的老鼠可以完全通过气味来识别和定位几米外的一块奶酪，即使空气中奶酪分子的浓度在这段距离上变化很大。大脑如何在如此广泛的刺激强度下保持知觉稳定，仍然是一个基本的、尚未回答的问题。小鼠鼻子中嗅觉感觉神经元的反应特性可能提供了部分答案。每一次嗅觉，吸入的气味分子都会激活感觉神经元的亚群，每个亚群都表达一种单一类型的气味受体。在低浓度下，当只有几个气味分子存在时，只有那些对特定气味表达最敏感受体的细胞才会被激活。然而，许多表达低亲和力受体的细胞也会在较高的浓度下被激活，这可能会降低气味的代表性。至关重要的是，无论浓度如何，表达高亲和力受体的感觉神经元总是在嗅觉中最早被激活。老鼠的大脑能否利用这种时间结构，在气味浓度不断变化的情况下保持稳定的气味表达？为了验证这一想法，我们同时记录了嗅球(OB)二尖瓣细胞的尖峰活动，这些细胞接受来自嗅觉感觉神经元的输入，以及它们的皮质目标-梨状皮质(PCX)的主神经元(PNS)，气味识别在那里编码。三叉神经核除在PCX抑制中间神经元上形成兴奋性突触外，还相互形成广泛的、远距离的“复发性”兴奋性突触。我们假设，这种架构使最早激活的PCX PN-因此最具选择性-PCX PN能够快速抑制选择性较低的PCX PN，帮助保持不同气味浓度的刺激特异性。我们通过在PCX PNS中选择性地表达破伤风毒素来直接测试这一想法，阻止它们兴奋其他PCX神经元的能力，但让它们对OB输入有反应。在对照组小鼠中，OB对不同气味的反应比PCX的反应更相关，对气味浓度的差异更敏感。单个OB神经元发出阵发性动作电位，具有强烈的气味特异性潜伏期和延长的反应，这与浓度密切相关。相比之下，PCX PNS在吸入后立即短暂兴奋，然后被强烈而持续的抑制迅速截断。为了确定这种抑制的来源，我们记录了PCX的前馈和反馈抑制中间神经元。仅由OB输入兴奋的前馈中间神经元表现出很少的气味诱发活动。相比之下，由PCX PNS兴奋而不是OB兴奋的反馈中间神经元显示出反映PN抑制的强健而持续的尖峰，表明PCX本身控制着自己抑制的时间和强度。我们通过用破伤风毒素沉默PCX中反复出现的兴奋性突触来消除这种皮质内通讯。这放大和延长了PCX的Pn反应，使它们的反应高度依赖于浓度，并取消了通过PCX尖峰活动稳定地预测不同浓度的气味识别的能力。吸入后反应最早的PCX细胞代表了气味的最特定和浓度不变的特征。广泛的、长距离的循环回路通过PCX广播它们的激活，招募强大的、持续的全局抑制，然后抑制随后的皮质活动。因此，循环电路有效地放大了最早到达的OB输入的影响，并打折了较晚到达的选择性较低的输入的影响。因此，PCX中的循环回路充当了一个精确计时的门，以确保只有最重要的信息才会进一步传递到大脑中，以指导老鼠的行为。动物依靠嗅觉寻找食物、吸引配偶和躲避捕食者。为了支持这些行为，他们必须能够识别不同气味浓度的气味。实现这种浓度不变性的神经回路操作仍不清楚。我们发现，尽管嗅球(OB)中的浓度依赖，但气味识别的表征在梨状皮质(PCX)下游被保留。吸入后最早反应的OB细胞在PCX神经元的稀疏亚群中驱动强烈的反应。经常性的侧支连接通过PCX传播它们的激活，招募全局反馈抑制，在嗅觉的剩余时间迅速截断和抑制皮质活动，忽略较慢的、浓度依赖的OB输入的影响。消除重复的伴随输出放大了PCX气味反应，使大脑皮层高度依赖浓度，并取消了浓度不变的身份解码。每当小鼠吸入气味时，挥发性分子就会激活鼻子中的气味受体，唤起嗅球的一系列活动。球茎细胞由最特定的受体驱动，因此最能代表气味刺激(奶酪)，总是最早做出反应。当这一信息传递到梨状皮质时，激活的主神经元(红细胞)招募抑制性神经元(绿细胞)，然后抑制皮质对随后较不特异的嗅球输入(如大蒜、鞋子或花)的反应，保留刺激的特性。
Objects can appear remarkably stable despite the often fickle cues they provide to our senses. For instance, a foraging mouse can identify and locate a piece of cheese several meters away entirely by smell, even though the concentration of airborne “cheese” molecules varies steeply over this distance. How the brain maintains perceptual stability across such widely ranging stimulus intensities remains a fundamental, unanswered question. The response properties of olfactory sensory neurons in the mouse’s nose may provide part of the answer. With each sniff, inhaled odorant molecules activate subsets of sensory neurons that each express a single type of odorant receptor. At low concentrations, when only a few odorant molecules are present, only those cells that express the most sensitive receptors for that particular odorant will be activated. However, many cells that express lower-affinity receptors will also be activated at higher concentrations, potentially degrading the odor representation. Crucially, the sensory neurons that express high-affinity receptors will always be activated earliest in the sniff, regardless of concentration. Could the mouse’s brain exploit this temporal structure to maintain stable odor representations despite changing odorant concentrations? To test this idea, we simultaneously recorded spiking activity from olfactory bulb (OB) mitral cells, which receive input from the olfactory sensory neurons, and from their cortical targets, principal neurons (PNs) in the piriform cortex (PCx), where odor identity is encoded. PNs form extensive, long-range “recurrent” excitatory synapses with each other in addition to forming excitatory synapses on PCx inhibitory interneurons. We hypothesized that this architecture enables the earliest activated—and therefore most selective—PCx PNs to rapidly inhibit less selective PCx PNs, helping to maintain stimulus specificity across odorant concentrations. We directly tested this idea by selectively expressing tetanus toxin in PCx PNs, blocking their ability to excite other PCx neurons but leaving them responsive to OB inputs. In control mice, OB responses to different odors were more correlated and were more sensitive to differences in odor concentration than responses in PCx. Individual OB neurons fired bursts of action potentials, with odor-specific latencies and prolonged responses that were strongly concentration-dependent. By contrast, PCx PNs were briefly excited immediately after inhalation and then rapidly truncated by strong and sustained Suppression. To identify the source of this suppression, we recorded from feedforward and feedback inhibitory interneurons in PCx. Feedforward interneurons, which are excited exclusively by OB inputs, exhibited little odor-evoked activity. By contrast, feedback interneurons, which are excited by PCx PNs but not by OB, showed robust and sustained spiking that mirrored PN suppression, indicating that PCx itself controls the timing and strength of its own suppression. We eliminated this intracortical communication by silencing recurrent excitatory synapses in PCx with tetanus toxin. This amplified and prolonged PCx PN responses, rendered their responses steeply concentration-dependent, and abolished the ability to stably predict odor identity across concentrations from PCx spiking activity. The PCx cells that respond earliest after inhalation represent the most odorant-specific and concentration-invariant features of the odor. The extensive, long-range recurrent circuitry broadcasts their activation across PCx, recruiting strong, sustained global inhibition that then suppresses subsequent cortical activity. Recurrent circuitry therefore effectively amplifies the impact of the earliest arriving OB inputs and discounts the impact of less-selective inputs that arrive later. Thus, the recurrent circuitry in the PCx acts as a precisely timed gate to ensure that only the most salient information is relayed further into the brain to guide the mouse’s behavior. Animals rely on olfaction to find food, attract mates, and avoid predators. To support these behaviors, they must be able to identify odors across different odorant concentrations. The neural circuit operations that implement this concentration invariance remain unclear.We found that despite concentration-dependence in the olfactory bulb (OB), representations of odor identity were preserved downstream, in the piriform cortex (PCx).The OB cells responding earliest after inhalation drove robust responses in sparse subsets of PCx neurons. Recurrent collateral connections broadcast their activation across the PCx, recruiting global feedback inhibition that rapidly truncated and suppressed cortical activity for the remainder of the sniff, discounting the impact of slower, concentration-dependent OB inputs. Eliminating recurrent collateral output amplified PCx odor responses rendered the cortex steeply concentration-dependent and abolished concentration-invariant identity decoding. Whenever a mouse inhales, volatile molecules activate odorant receptors in the nose, evoking sequences of activity in the olfactory bulb. Bulb cells driven by the most specific receptors, which therefore best represent the odor stimulus (cheese), will always respond earliest. When this information is relayed to piriform cortex, activated principal neurons (red cells) recruit inhibitory neurons (green cells) that then suppress cortical responses to subsequent, less-specific olfactory bulb input (such as garlic, shoe, or flower), preserving the identity of the stimulus.
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影响因子：
16.6
作者：
Arneodo EM;Penikis KB;Rabinowitz N;Licata A;Cichy A;Zhang J;Bozza T;Rinberg D
通讯作者：
Rinberg D
DOI：
10.3389/fneng.2011.00021
发表时间：
2011-11-16
期刊：
Frontiers in neuroengineering
影响因子：
--
作者：
Cleland TA;Chen SY;Hozer KW;Ukatu HN;Wong KJ;Zheng F
通讯作者：
Zheng F
DOI：
10.1111/j.1460-9568.2009.06644.x
发表时间：
2009-03
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Homma R;Cohen LB;Kosmidis EK;Youngentob SL
通讯作者：
Youngentob SL
影响因子：
16.2
作者：
Fukunaga, Izumi;Berning, Manuel;Schaefer, Andreas T.
通讯作者：
Schaefer, Andreas T.
影响因子：
64.8
作者：
HOPFIELD, JJ
通讯作者：
HOPFIELD, JJ