Support for a synaptic chain model of neuronal sequence generation

In songbirds, the remarkable temporal precision of song is generated by a sparse sequence of bursts in the premotor nucleus HVC. To distinguish between two possible classes of models of neural sequence generation, we carried out intracellular recordings of HVC neurons in singing zebra finches (Taeniopygia guttata). We found that the subthreshold membrane potential is characterized by a large, rapid depolarization 5-10 ms before burst onset, consistent with a synaptically connected chain of neurons in HVC. We found no evidence for the slow membrane potential modulation predicted by models in which burst timing is controlled by subthreshold dynamics. Furthermore, bursts ride on an underlying depolarization of ～10-ms duration, probably the result of a regenerative calcium spike within HVC neurons that could facilitate the propagation of activity through a chain network with high temporal precision. Our results provide insight into the fundamental mechanisms by which neural circuits can generate complex sequential behaviours.     

鸣禽鸣啭控制核团内GABA能神经元的分布研究

应用免疫组化方法对鸣禽粟鹀(Emberiza rutila)鸣啭控制核团内GABA能神经元的分布进行了研究，在高级发声中枢(HVC，high vocal center)，古纹状体粗核(RA，the robust nucleus of the archistrialum)，X区(Arca X)3个前脑核团内有GABA样免疫反应出现．HVC和RA中GABA能神经元胞体大小存在性别和季节间的差异．结果提示GABA能神经元可能参与了鸣禽鸣啭的产生和鸣啭学习。     

多巴胺对鸣禽发声相关神经元活动的调控

鸣禽多巴胺(DA)神经元主要分布于中脑腹侧被盖区-黑质体致密部(VTA-SNc复合体)和中脑导水管周围灰质(PAG),并分别发出纤维投射至鸣唱控制核团前脑纹状X区、弓状皮质栎核(RA)和高级发声中枢(HVC).近年研究表明,中脑向鸣唱控制核团中释放的DA可以调控鸣唱控制核团中神经元的活动,进而调节鸣禽的鸣唱行为.该文对近年来,多巴胺对鸣禽发声相关神经元活动的调控研究做一综述.     

Choice-specific sequences in parietal cortex during a virtual-navigation decision task

The posterior parietal cortex (PPC) has an important role in many cognitive behaviours; however, the neural circuit dynamics underlying PPC function are not well understood. Here we optically imaged the spatial and temporal activity patterns of neuronal populations in mice performing a PPC-dependent task that combined a perceptual decision and memory-guided navigation in a virtual environment. Individual neurons had transient activation staggered relative to one another in time, forming a sequence of neuronal activation spanning the entire length of a task trial. Distinct sequences of neurons were triggered on trials with opposite behavioural choices and defined divergent, choice-specific trajectories through a state space of neuronal population activity. Cells participating in the different sequences and at distinct time points in the task were anatomically intermixed over microcircuit length scales (<100 micrometres). During working memory decision tasks, the PPC may therefore perform computations through sequence-based circuit dynamics, rather than long-lived stable states, implemented using anatomically intermingled microcircuits.     

Temporal patterns of human cortical activity reflect tone sequence structure

Despite growing interest in temporal aspects of auditory neural processing, little is known about large-scale timing patterns of brain activity during the perception of auditory sequences. This is partly because it has not been possible to distinguish stimulus-related activity from other, endogenous brain signals recorded by electrical or magnetic sensors. Here we use amplitude modulation of unfamiliar, approximately 1-minute-long tone sequences to label stimulus-related magnetoencephalographic neural activity in human subjects. We show that temporal patterns of activity recorded over particular brain regions track the pitch contour of tone sequences, with the accuracy of tracking increasing as tone sequences become more predictable in structure. In contrast, temporal synchronization between recording locations, particularly between sites over the left posterior hemisphere and the rest of the brain, is greatest when sequences have melody-like statistical properties, which may reflect the perceptual integration of local and global pitch patterns in melody-like sequences. This method is particularly well suited to studying temporal neural correlates of complex auditory sequences (such as speech or music) which engage multiple brain areas as perception unfolds in time.     

Perception of sniff phase in mouse olfaction

Olfactory systems encode odours by which neurons respond and by when they respond. In mammals, every sniff evokes a precise, odour-specific sequence of activity across olfactory neurons. Likewise, in a variety of neural systems, ranging from sensory periphery to cognitive centres, neuronal activity is timed relative to sampling behaviour and/or internally generated oscillations. As in these neural systems, relative timing of activity may represent information in the olfactory system. However, there is no evidence that mammalian olfactory systems read such cues. To test whether mice perceive the timing of olfactory activation relative to the sniff cycle ('sniff phase'), we used optogenetics in gene-targeted mice to generate spatially constant, temporally controllable olfactory input. Here we show that mice can behaviourally report the sniff phase of optogenetically driven activation of olfactory sensory neurons. Furthermore, mice can discriminate between light-evoked inputs that are shifted in the sniff cycle by as little as 10 milliseconds, which is similar to the temporal precision of olfactory bulb odour responses. Electrophysiological recordings in the olfactory bulb of awake mice show that individual cells encode the timing of photoactivation in relation to the sniff in both the timing and the amplitude of their responses. Our work provides evidence that the mammalian olfactory system can read temporal patterns, and suggests that timing of activity relative to sampling behaviour is a potent cue that may enable accurate olfactory percepts to form quickly.     

Activity of striatal neurons reflects dynamic encoding and recoding of procedural memories

Learning to perform a behavioural procedure as a well-ingrained habit requires extensive repetition of the behavioural sequence, and learning not to perform such behaviours is notoriously difficult. Yet regaining a habit can occur quickly, with even one or a few exposures to cues previously triggering the behaviour. To identify neural mechanisms that might underlie such learning dynamics, we made long-term recordings from multiple neurons in the sensorimotor striatum, a basal ganglia structure implicated in habit formation, in rats successively trained on a reward-based procedural task, given extinction training and then given reacquisition training. The spike activity of striatal output neurons, nodal points in cortico-basal ganglia circuits, changed markedly across multiple dimensions during each of these phases of learning. First, new patterns of task-related ensemble firing successively formed, reversed and then re-emerged. Second, task-irrelevant firing was suppressed, then rebounded, and then was suppressed again. These changing spike activity patterns were highly correlated with changes in behavioural performance. We propose that these changes in task representation in cortico-basal ganglia circuits represent neural equivalents of the explore-exploit behaviour characteristic of habit learning.     

去势对成年雄性斑胸草雀HVC神经元电生理特性的影响

鸣唱控制系统的高级发声中枢HVC（high vocal center）是发声运动通路和前端脑通路的始端，是发声行为的起始控制脑区，亦可接受听觉信号的输入及反馈，是鸣禽鸣唱调控最为重要的脑区.以往研究表明,雄激素及其代谢产物对鸣禽鸣唱控制有重要作用.去势显著改变鸣禽体内激素含量，进而影响鸣禽鸣曲稳定性，但其具体机制尚未阐明.我们运用全细胞膜片钳记录法，在离体细胞水平研究了去势引起的雄激素水平降低对HVC不同神经元电生理特性的影响.研究结果显示,去势组与对照组相比，投射神经元HVCRA，HVCX膜输入电阻减小，膜时间常数降低，动作电位后超极化幅值升高及达到峰值时间延长，表明雄激素可以提高两类投射神经元的兴奋性. 综上所述，雄激素可以一定程度上提高HVC神经元的兴奋性，雄激素可增强HVC对发声运动通路（vocal motor pathway,VMP)的控制，抑制前端脑通路(anterior forebrain pathway,AFP)来实现维持鸣曲的稳定.     

鸣禽栗巫鸟前脑高级发声中枢及其架区的纤维联系

用ＣＢ－ＨＲＰ顺、逆行追踪的方法,研究了鸣禽栗巫鸟前脑高级发声中枢（ＨＶＣ）及其周围架区（ｓｈｅｌｆ）的传入、传出投射．结果表明,ＨＶＣ接受丘脑葡萄形核（Ｕｖａ）、新纹状体前部巨细胞核内侧部（ｍＭＡＮ）、新纹状体界面核（ＮＩｆ）的传入投射,并发出纤维投射至旁嗅叶的Ｘ区和古纹状体粗核（ＲＡ）;还通过架区间接联系听区复合体（Ｌ区）及脑桥的蓝斑核（Ｌｏｃ）等．     

成年雄性斑胸草雀脑多巴胺D1受体的分布

多巴胺是脑内关键的神经递质,它通过与多巴胺受体的作用及其下游的一系列反应来影响基因表达、神经调节和行为活动.在成年鸣禽中,中脑多巴胺能神经元投射到X区、HVC和RA等鸣唱相关核团,释放多巴胺的量受一定社会情境的影响,从而表现出directed song和undirected song等不同鸣唱行为.获得斑胸草雀脑中多巴胺受体的表达情况,为与社会情境有关的鸣唱行为及其他和多巴胺相关的行为活动的神经机制探究提供了基础,并可促进行为学、电生理等方面的研究.我们发现D1受体在斑胸草雀脑中的分布与其mRNA的分布基本一致:在脑的绝大部分区域都有分布;主要鸣唱核团HVC和RA有表达,与其周围区域差异不明显;LMAN中表达量较少;DLM中的表达量较高,并与其周围区域差异明显.但是纹状体内的表达与其周围区域的差异性没有mRNA明显;GCT中的表达量较多,与周围区域差异明显.     

Short-term memory in olfactory network dynamics

Neural assemblies in a number of animal species display self-organized, synchronized oscillations in response to sensory stimuli in a variety of brain areas. In the olfactory system of insects, odour-evoked oscillatory synchronization of antennal lobe projection neurons (PNs) is superimposed on slower and stimulus-specific temporal activity patterns. Hence, each odour activates a specific and dynamic projection neuron assembly whose evolution during a stimulus is locked to the oscillation clock. Here we examine, using locusts, the changes in population dynamics of projection-neuron assemblies over repeated odour stimulations, as would occur when an animal first encounters and then repeatedly samples an odour for identification or localization. We find that the responses of these assemblies rapidly decrease in intensity, while they show a marked increase in spike time precision and inter-neuronal oscillatory coherence. Once established, this enhanced precision in the representation endures for several minutes. This change is stimulus-specific, and depends on events within the antennal lobe circuits, independent of olfactory receptor adaptation: it may thus constitute a form of sensory memory. Our results suggest that this progressive change in olfactory network dynamics serves to converge, over repeated odour samplings, on a more precise and readily classifiable odour representation, using relational information contained across neural assemblies.     

Categorization of behavioural sequences in the prefrontal cortex

Although it has long been thought that the prefrontal cortex of primates is involved in the integrative regulation of behaviours, the neural architecture underlying specific aspects of cognitive behavioural planning has yet to be clarified. If subjects are required to remember a large number of complex motor sequences and plan to execute each of them individually, categorization of the sequences according to the specific temporal structure inherent in each subset of sequences serves to facilitate higher-order planning based on memory. Here we show, using these requirements, that cells in the lateral prefrontal cortex selectively exhibit activity for a specific category of behavioural sequences, and that categories of behaviours, embodied by different types of movement sequences, are represented in prefrontal cells during the process of planning. This cellular activity implies the generation of neural representations capable of storing structured event complexes at an abstract level, exemplifying the development of macro-structured action knowledge in the lateral prefrontal cortex.     

白腰文鸟古纹状体粗核神经纤维联系的研究

本实验采用辣根过氧化物酶(HRP)顺逆行追踪法,对白腰文鸟的古纹状体粗核(RA)的纤维联系进行了研究,实验表明:端脑内发声控制的主要运动神经核团——古纹状体粗核(RA)除了与发声控制神经核团有纤维联系之外,还与其他神经核团有纤维联系.     

Odour-plume dynamics influence the brain's olfactory code

The neural computations used to represent olfactory information in the brain have long been investigated. Recent studies in the insect antennal lobe suggest that precise temporal and/or spatial patterns of activity underlie the recognition and discrimination of different odours, and that these patterns may be strengthened by associative learning. It remains unknown, however, whether these activity patterns persist when odour intensity varies rapidly and unpredictably, as often occurs in nature. Here we show that with naturally intermittent odour stimulation, spike patterns recorded from moth antennal-lobe output neurons varied predictably with the fine-scale temporal dynamics and intensity of the odour. These data support the hypothesis that olfactory circuits compensate for contextual variations in the stimulus pattern with high temporal precision. The timing of output neuron activity is constantly modulated to reflect ongoing changes in stimulus intensity and dynamics that occur on a millisecond timescale.     

A basal ganglia pacemaker formed by the subthalamic nucleus and external globus pallidus.

The subthalamic nucleus of the basal ganglia (STN) is important for normal movement as well as in movement disorders. Lesioning or deep-brain stimulation of the STN can alleviate resting tremor in Parkinson's disease. The STN and its target nuclei display synchronized oscillatory burst discharge at low frequencies, some of which correlate with tremor, but the mechanism underlying this synchronized bursting is unknown. Here we show that the excitatory STN and inhibitory, external globus pallidus (GPe) form a feedback system that engages in synchronized bursting. In mature organotypic cortex-striatum-STN-GPe cultures, neurons in the STN and GPe spontaneously produce synchronized oscillating bursts at 0.4, 0.8 and 1.8 Hz. Pallidal lesion abolishes this bursting, whereas cortical lesion favours bursting at 0.8 Hz. Pallidal bursts, although weaker than STN bursts, were required for synchronized oscillatory burst generation by recruitment of subthalmic rebound excitation. We propose that the STN and GPe constitute a central pacemaker modulated by striatal inhibition of GPe neurons. This pacemaker could be responsible for synchronized oscillatory activity in the normal and pathological basal ganglia.     

Preplay of future place cell sequences by hippocampal cellular assemblies

During spatial exploration, hippocampal neurons show a sequential firing pattern in which individual neurons fire specifically at particular locations along the animal's trajectory (place cells). According to the dominant model of hippocampal cell assembly activity, place cell firing order is established for the first time during exploration, to encode the spatial experience, and is subsequently replayed during rest or slow-wave sleep for consolidation of the encoded experience. Here we report that temporal sequences of firing of place cells expressed during a novel spatial experience occurred on a significant number of occasions during the resting or sleeping period preceding the experience. This phenomenon, which is called preplay, occurred in disjunction with sequences of replay of a familiar experience. These results suggest that internal neuronal dynamics during resting or sleep organize hippocampal cellular assemblies into temporal sequences that contribute to the encoding of a related novel experience occurring in the future.     

Distinct representations of olfactory information in different cortical centres

Sensory information is transmitted to the brain where it must be processed to translate stimulus features into appropriate behavioural output. In the olfactory system, distributed neural activity in the nose is converted into a segregated map in the olfactory bulb. Here we investigate how this ordered representation is transformed in higher olfactory centres in mice. We have developed a tracing strategy to define the neural circuits that convey information from individual glomeruli in the olfactory bulb to the piriform cortex and the cortical amygdala. The spatial order in the bulb is discarded in the piriform cortex; axons from individual glomeruli project diffusely to the piriform without apparent spatial preference. In the cortical amygdala, we observe broad patches of projections that are spatially stereotyped for individual glomeruli. These projections to the amygdala are overlapping and afford the opportunity for spatially localized integration of information from multiple glomeruli. The identification of a distributive pattern of projections to the piriform and stereotyped projections to the amygdala provides an anatomical context for the generation of learned and innate behaviours.     

Precise auditory-vocal mirroring in neurons for learned vocal communication

Brain mechanisms for communication must establish a correspondence between sensory and motor codes used to represent the signal. One idea is that this correspondence is established at the level of single neurons that are active when the individual performs a particular gesture or observes a similar gesture performed by another individual. Although neurons that display a precise auditory-vocal correspondence could facilitate vocal communication, they have yet to be identified. Here we report that a certain class of neurons in the swamp sparrow forebrain displays a precise auditory-vocal correspondence. We show that these neurons respond in a temporally precise fashion to auditory presentation of certain note sequences in this songbird's repertoire and to similar note sequences in other birds' songs. These neurons display nearly identical patterns of activity when the bird sings the same sequence, and disrupting auditory feedback does not alter this singing-related activity, indicating it is motor in nature. Furthermore, these neurons innervate striatal structures important for song learning, raising the possibility that singing-related activity in these cells is compared to auditory feedback to guide vocal learning.     

Neuronal filtering of multiplexed odour representations

Neuronal activity patterns contain information in their temporal structure, indicating that information transfer between neurons may be optimized by temporal filtering. In the zebrafish olfactory bulb, subsets of output neurons (mitral cells) engage in synchronized oscillations during odour responses, but information about odour identity is contained mostly in non-oscillatory firing rate patterns. Using optogenetic manipulations and odour stimulation, we found that firing rate responses of neurons in the posterior zone of the dorsal telencephalon (Dp), a target area homologous to olfactory cortex, were largely insensitive to oscillatory synchrony of mitral cells because passive membrane properties and synaptic currents act as low-pass filters. Nevertheless, synchrony influenced spike timing. Moreover, Dp neurons responded primarily during the decorrelated steady state of mitral cell activity patterns. Temporal filtering therefore tunes Dp neurons to components of mitral cell activity patterns that are particularly informative about precise odour identity. These results demonstrate how temporal filtering can extract specific information from multiplexed neuronal codes.