Neural encoding of individual words and faces by the human hippocampus and amygdala

Patients with lesions in the medial temporal lobe (MTL) of the brain, which includes the hippocampus, amygdala and parahippocampal gyrus, are severely impaired in their ability to remember and recognize words or faces which they saw only a short time ago. These lesions also prevent the effect of word repetition on cortical event-related potentials that are associated with these tasks. We have been able to study the response of individual neurons in the human medial temporal lobe to such delayed recognition tasks in epileptic patients undergoing neurosurgery. We found that some MTL neurons preferentially fired on sight of one particular word from a set of ten words used in a memory task, and others fired in response to one particular face. This stimulus-specific firing was maximal during the time that the neocortical event potentials are most sensitive to stimulus repetition, suggesting that the MTL contributes specific information to the cortex during the retrieval of recent memories.     

Diurnal modulation of pacemaker potentials and calcium current in the mammalian circadian clock

The central biological clock of the mammalian brain is located in the suprachiasmatic nucleus. This hypothalamic region contains neurons that generate a circadian rhythm on a single-cell basis. Clock cells transmit their circadian timing signals to other brain areas by diurnal modulation of their spontaneous firing rate. The intracellular mechanism underlying rhythm generation is thought to consist of one or more self-regulating molecular loops, but it is unknown how these loops interact with the plasma membrane to modulate the ionic conductances that regulate firing behaviour. Here we demonstrate a diurnal modulation of Ca2+ current in suprachiasmatic neurons. This current strongly contributes to the generation of spontaneous oscillations in membrane potential, which occur selectively during daytime and are tightly coupled to spike generation. Thus, day-night modulation of Ca2+ current is a central step in transducing the intracellular cycling of molecular clocks to the rhythm in spontaneous firing rate.     

Spontaneously emerging cortical representations of visual attributes

Spontaneous cortical activity--ongoing activity in the absence of intentional sensory input--has been studied extensively, using methods ranging from EEG (electroencephalography), through voltage sensitive dye imaging, down to recordings from single neurons. Ongoing cortical activity has been shown to play a critical role in development, and must also be essential for processing sensory perception, because it modulates stimulus-evoked activity, and is correlated with behaviour. Yet its role in the processing of external information and its relationship to internal representations of sensory attributes remains unknown. Using voltage sensitive dye imaging, we previously established a close link between ongoing activity in the visual cortex of anaesthetized cats and the spontaneous firing of a single neuron. Here we report that such activity encompasses a set of dynamically switching cortical states, many of which correspond closely to orientation maps. When such an orientation state emerged spontaneously, it spanned several hypercolumns and was often followed by a state corresponding to a proximal orientation. We suggest that dynamically switching cortical states could represent the brain's internal context, and therefore reflect or influence memory, perception and behaviour.     

基于自然图像认知的大鼠上丘神经元恐惧信息编码机制

为了探究大鼠对自然图像的认知效果以及在自然图像认知过程中上丘(superior colliculus, SC)神经元的恐惧信息编码机制,采用条件性恐惧联结训练方法,设计了基于三种不同情感属性自然图像的实验方案(恐惧:"蛇"、中性:"树"、奖励:"鼠粮"),对大鼠进行了视觉认知训练。首先,从行为学分析了大鼠对具有不同情感意义自然图像的认知效果;其次,采用第一动作电位延时(first spike latency, FSL)以及Spike(峰电位)平均发放率两种编码方法,研究了大鼠上丘神经元在自然图像认知学习过程中的恐惧信息编码机制。结果表明,大鼠对奖励、恐惧、中性三种图像的抉择正确率分别在第6、22、26 d达到了75%基准线。训练后,在恐惧图像的刺激作用下,大鼠上丘神经元集群的平均FSL值显著低于训练前,且神经元集群的Spike发放率显著提高。这些结果揭示了恐惧信息能够激活大鼠上丘脑区,并通过SC脑区实现恐惧信息快速传递与表征。     

Attractor dynamics of network UP states in the neocortex

The cerebral cortex receives input from lower brain regions, and its function is traditionally considered to be processing that input through successive stages to reach an appropriate output. However, the cortical circuit contains many interconnections, including those feeding back from higher centres, and is continuously active even in the absence of sensory inputs. Such spontaneous firing has a structure that reflects the coordinated activity of specific groups of neurons. Moreover, the membrane potential of cortical neurons fluctuates spontaneously between a resting (DOWN) and a depolarized (UP) state, which may also be coordinated. The elevated firing rate in the UP state follows sensory stimulation and provides a substrate for persistent activity, a network state that might mediate working memory. Using two-photon calcium imaging, we reconstructed the dynamics of spontaneous activity of up to 1,400 neurons in slices of mouse visual cortex. Here we report the occurrence of synchronized UP state transitions ('cortical flashes') that occur in spatially organized ensembles involving small numbers of neurons. Because of their stereotyped spatiotemporal dynamics, we conclude that network UP states are circuit attractors--emergent features of feedback neural networks that could implement memory states or solutions to computational problems.     

The primate amygdala represents the positive and negative value of visual stimuli during learning

Visual stimuli can acquire positive or negative value through their association with rewards and punishments, a process called reinforcement learning. Although we now know a great deal about how the brain analyses visual information, we know little about how visual representations become linked with values. To study this process, we turned to the amygdala, a brain structure implicated in reinforcement learning. We recorded the activity of individual amygdala neurons in monkeys while abstract images acquired either positive or negative value through conditioning. After monkeys had learned the initial associations, we reversed image value assignments. We examined neural responses in relation to these reversals in order to estimate the relative contribution to neural activity of the sensory properties of images and their conditioned values. Here we show that changes in the values of images modulate neural activity, and that this modulation occurs rapidly enough to account for, and correlates with, monkeys' learning. Furthermore, distinct populations of neurons encode the positive and negative values of visual stimuli. Behavioural and physiological responses to visual stimuli may therefore be based in part on the plastic representation of value provided by the amygdala.     

Invariant visual representation by single neurons in the human brain

It takes a fraction of a second to recognize a person or an object even when seen under strikingly different conditions. How such a robust, high-level representation is achieved by neurons in the human brain is still unclear. In monkeys, neurons in the upper stages of the ventral visual pathway respond to complex images such as faces and objects and show some degree of invariance to metric properties such as the stimulus size, position and viewing angle. We have previously shown that neurons in the human medial temporal lobe (MTL) fire selectively to images of faces, animals, objects or scenes. Here we report on a remarkable subset of MTL neurons that are selectively activated by strikingly different pictures of given individuals, landmarks or objects and in some cases even by letter strings with their names. These results suggest an invariant, sparse and explicit code, which might be important in the transformation of complex visual percepts into long-term and more abstract memories.     

浅谈教师声音形象的塑造

教师形象的塑造往往关注教师的内部形象和外部形象 ,而忽略这两种形象的最重要的转换格式———教师的声音形象。通过对教师声音形象的魅力触角———音色、音量、语气、语速等主要存在形态的探讨 ,揭示它们作为语言结构的情感张力 ,明确教师声音形象美的几个指标 ,为教师形象的塑造提供一些想法     

A neuronal mechanism for sensory gating during locomotion in a vertebrate

The response of the foot to touch during walking depends on whether it is in the air or on the ground. In most animals, reflex responses to external stimuli are similarly adapted to their timing in the locomotor cycle, but there is only fragmentary information about the neural mechanisms involved. In arthropods, reflex modulation can occur in the sensory receptors themselves and in neurons that discharge during locomotion. By recording with dye-filled microelectrodes from neurons in the spinal cord of frog embryos, we describe reflex modulation at the level of sensory interneurons. Sensory inputs from skin receptors excite a specific class of spinal sensory interneuron whose activity leads to reflex bending of the body away from the stimulus. During swimming, these inputs are gated by rhythmic postsynaptic inhibition, so that sensory drive reaches motor neurons only at phases in the locomotor cycle when the resulting contraction would likewise turn the embryo away from the stimulated side. Such gating of sensory pathways could be a general feature of all locomotor systems where responses to sensory stimuli need to be adapted to the phase of locomotion.     

虹膜纹理归一化的圆心偏差校正算法

从眼生理学和图像采集两个角度，分析了造成虹膜内外圆心偏差的原因，并有针对性地提出了第一、第二圆心偏差校正模型．分别采用以上校正算法和传统算法对400幅虹膜图像进行处理，通过对校正结果的分析，发现与传统的虹膜纹理归一化算法相比，该校正算法可有效地排除内外圆偏差的干扰，使虹膜识别的准确性获得显著提高．实验证明，该虹膜纹理归一化校正算法是有效的．     

Small modulation of ongoing cortical dynamics by sensory input during natural vision

During vision, it is believed that neural activity in the primary visual cortex is predominantly driven by sensory input from the environment. However, visual cortical neurons respond to repeated presentations of the same stimulus with a high degree of variability. Although this variability has been considered to be noise owing to random spontaneous activity within the cortex, recent studies show that spontaneous activity has a highly coherent spatio-temporal structure. This raises the possibility that the pattern of this spontaneous activity may shape neural responses during natural viewing conditions to a larger extent than previously thought. Here, we examine the relationship between spontaneous activity and the response of primary visual cortical neurons to dynamic natural-scene and random-noise film images in awake, freely viewing ferrets from the time of eye opening to maturity. The correspondence between evoked neural activity and the structure of the input signal was weak in young animals, but systematically improved with age. This improvement was linked to a shift in the dynamics of spontaneous activity. At all ages including the mature animal, correlations in spontaneous neural firing were only slightly modified by visual stimulation, irrespective of the sensory input. These results suggest that in both the developing and mature visual cortex, sensory evoked neural activity represents the modulation and triggering of ongoing circuit dynamics by input signals, rather than directly reflecting the structure of the input signal itself.     

Spatio-temporal correlations and visual signalling in a complete neuronal population

Statistical dependencies in the responses of sensory neurons govern both the amount of stimulus information conveyed and the means by which downstream neurons can extract it. Although a variety of measurements indicate the existence of such dependencies, their origin and importance for neural coding are poorly understood. Here we analyse the functional significance of correlated firing in a complete population of macaque parasol retinal ganglion cells using a model of multi-neuron spike responses. The model, with parameters fit directly to physiological data, simultaneously captures both the stimulus dependence and detailed spatio-temporal correlations in population responses, and provides two insights into the structure of the neural code. First, neural encoding at the population level is less noisy than one would expect from the variability of individual neurons: spike times are more precise, and can be predicted more accurately when the spiking of neighbouring neurons is taken into account. Second, correlations provide additional sensory information: optimal, model-based decoding that exploits the response correlation structure extracts 20% more information about the visual scene than decoding under the assumption of independence, and preserves 40% more visual information than optimal linear decoding. This model-based approach reveals the role of correlated activity in the retinal coding of visual stimuli, and provides a general framework for understanding the importance of correlated activity in populations of neurons.     

Identification of protein pheromones that promote aggressive behaviour

Mice use pheromones, compounds emitted and detected by members of the same species, as cues to regulate social behaviours such as pup suckling, aggression and mating. Neurons that detect pheromones are thought to reside in at least two separate organs within the nasal cavity: the vomeronasal organ (VNO) and the main olfactory epithelium (MOE). Each pheromone ligand is thought to activate a dedicated subset of these sensory neurons. However, the nature of the pheromone cues and the identity of the responding neurons that regulate specific social behaviours are largely unknown. Here we show, by direct activation of sensory neurons and analysis of behaviour, that at least two chemically distinct ligands are sufficient to promote male-male aggression and stimulate VNO neurons. We have purified and analysed one of these classes of ligand and found its specific aggression-promoting activity to be dependent on the presence of the protein component of the major urinary protein (MUP) complex, which is known to comprise specialized lipocalin proteins bound to small organic molecules. Using calcium imaging of dissociated vomeronasal neurons (VNs), we have determined that the MUP protein activates a sensory neuron subfamily characterized by the expression of the G-protein Galpha(o) subunit (also known as Gnao) and Vmn2r putative pheromone receptors (V2Rs). Genomic analysis indicates species-specific co-expansions of MUPs and V2Rs, as would be expected among pheromone-signalling components. Finally, we show that the aggressive behaviour induced by the MUPs occurs exclusively through VNO neuronal circuits. Our results substantiate the idea of MUP proteins as pheromone ligands that mediate male-male aggression through the accessory olfactory neural pathway.     

Catecholamine receptor polymorphisms affect decision-making in C. elegans

Innate behaviours are flexible: they change rapidly in response to transient environmental conditions, and are modified slowly by changes in the genome. A classical flexible behaviour is the exploration-exploitation decision, which describes the time at which foraging animals choose to abandon a depleting food supply. We have used quantitative genetic analysis to examine the decision to leave a food patch in Caenorhabditis elegans. Here we show that patch-leaving is a multigenic trait regulated in part by naturally occurring non-coding polymorphisms in tyra-3 (tyramine receptor 3), which encodes a G-protein-coupled catecholamine receptor related to vertebrate adrenergic receptors. tyra-3 acts in sensory neurons that detect environmental cues, suggesting that the internal catecholamines detected by tyra-3 regulate responses to external conditions. These results indicate that genetic variation and environmental cues converge on common circuits to regulate behaviour, and suggest that catecholamines have an ancient role in regulating behavioural decisions.     

Neurons compute internal models of the physical laws of motion

A critical step in self-motion perception and spatial awareness is the integration of motion cues from multiple sensory organs that individually do not provide an accurate representation of the physical world. One of the best-studied sensory ambiguities is found in visual processing, and arises because of the inherent uncertainty in detecting the motion direction of an untextured contour moving within a small aperture. A similar sensory ambiguity arises in identifying the actual motion associated with linear accelerations sensed by the otolith organs in the inner ear. These internal linear accelerometers respond identically during translational motion (for example, running forward) and gravitational accelerations experienced as we reorient the head relative to gravity (that is, head tilt). Using new stimulus combinations, we identify here cerebellar and brainstem motion-sensitive neurons that compute a solution to the inertial motion detection problem. We show that the firing rates of these populations of neurons reflect the computations necessary to construct an internal model representation of the physical equations of motion.     

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.     

汉语具象性复合词初探

在汉语复合词当中,有相当一部分词具有非常强的形象色彩,体现出明显的具象性,例如"席卷、瓜分、狗尾巴草"等,我们称之为具象性复合词。本文一方面分析了这类词的内部构造方式、外部表现功能;另一方面,还从认知角度出发,指出具象式复合词的隐喻实质及其折射出的人类认知规律。     

腺苷及其阻断剂茶碱对大鼠尾状核脑薄片神经元自发放电的影响

本实验采用脑薄片电活动胞外记录法，研究腺苷及其非特异性阻断剂茶碱对大鼠尾状核脑薄片神经元自发放电的影响，在记录的３１个细胞中，对２１个细胞灌流了腺苷，其中３个细胞自发放电频率无明显变化，占３／２１＝１４２８％；在另外１８个对腺苷有反应的细胞中，有６个细胞自发放电频率增加，占６／２１＝２８５７％；有１２个细胞自发放电频率减少，占１２／２１＝５７２２％。腺苷的兴奋和抑制效应都有量效关系。茶碱对大鼠尾状核神经元自发放电的效应与腺苷相反。结果提示，大鼠尾状核内存在两种类型的腺苷受体：Ａ１和Ａ２；腺苷对大鼠尾状核脑片神经元自发放电的抑制效应是通过激活Ａ１受体实现的，而其兴奋效应是由于激活了Ａ２受体。     

Neuronal basis of age-related working memory decline

Many of the cognitive deficits of normal ageing (forgetfulness, distractibility, inflexibility and impaired executive functions) involve prefrontal cortex (PFC) dysfunction. The PFC guides behaviour and thought using working memory, which are essential functions in the information age. Many PFC neurons hold information in working memory through excitatory networks that can maintain persistent neuronal firing in the absence of external stimulation. This fragile process is highly dependent on the neurochemical environment. For example, elevated cyclic-AMP signalling reduces persistent firing by opening HCN and KCNQ potassium channels. It is not known if molecular changes associated with normal ageing alter the physiological properties of PFC neurons during working memory, as there have been no in vivo recordings, to our knowledge, from PFC neurons of aged monkeys. Here we characterize the first recordings of this kind, revealing a marked loss of PFC persistent firing with advancing age that can be rescued by restoring an optimal neurochemical environment. Recordings showed an age-related decline in the firing rate of DELAY neurons, whereas the firing of CUE neurons remained unchanged with age. The memory-related firing of aged DELAY neurons was partially restored to more youthful levels by inhibiting cAMP signalling, or by blocking HCN or KCNQ channels. These findings reveal the cellular basis of age-related cognitive decline in dorsolateral PFC, and demonstrate that physiological integrity can be rescued by addressing the molecular needs of PFC circuits.