A glycine receptor is involved in the organization of swimming movements in an invertebrate chordate

Background  

Rhythmic motor patterns for locomotion in vertebrates are generated in spinal cord neural networks known as spinal Central Pattern Generators (CPGs). A key element in pattern generation is the role of glycinergic synaptic transmission by interneurons that cross the cord midline and inhibit contralaterally-located excitatory neurons. The glycinergic inhibitory drive permits alternating and precisely timed motor output during locomotion such as walking or swimming. To understand better the evolution of this system we examined the physiology of the neural network controlling swimming in an invertebrate chordate relative of vertebrates, the ascidian larva Ciona intestinalis.     

Period 2 regulates neural stem/progenitor cell proliferation in the adult hippocampus

Background  

Newborn granule neurons are generated from proliferating neural stem/progenitor cells and integrated into mature synaptic networks in the adult dentate gyrus of the hippocampus. Since light/dark variations of the mitotic index and DNA synthesis occur in many tissues, we wanted to unravel the role of the clock-controlled Period2 gene (mPer2) in timing cell cycle kinetics and neurogenesis in the adult DG.     

Protein fingerprints of cultured CA3-CA1 hippocampal neurons: comparative analysis of the distribution of synaptosomal and cytosolic proteins

Background  

All studies aimed at understanding complex molecular changes occurring at synapses face the problem of how a complete view of the synaptic proteome and of its changes can be efficiently met. This is highly desirable when synaptic plasticity processes are analyzed since the structure and the biochemistry of neurons and synapses get completely reshaped. Because most molecular studies of synapses are nowadays mainly or at least in part based on protein extracts from neuronal cultures, this is not a feasible option: these simplified versions of the brain tissue on one hand provide an homogeneous pure population of neurons but on the other yield only tiny amounts of proteins, many orders of magnitude smaller than conventional brain tissue. As a way to overcome this limitation and to find a simple way to screen for protein changes at cultured synapses, we have produced and characterized two dimensional electrophoresis (2DE) maps of the synaptic proteome of CA3-CA1 hippocampal neurons in culture.     

Mutual and intermittent enhancements of synchronization transitions by autaptic and synaptic delay in scale-free neuron networks

In neural networks, there exist both synaptic delays among different neurons and autaptic self-feedback delays in a neuron itself. In this paper, we study synchronization transitions induced by synaptic and autaptic delays in scale-free neuron networks, mainly exploring how these two time delays affect synchronization transitions induced by each other. It is found that the synchronization transitions induced by synaptic (autaptic) delay are intermittently enhanced when autaptic (synaptic) delay is varied. There are optimal autaptic strength and synaptic coupling strength by which the synchronization transitions induced by autaptic and synaptic delays become strongest. The underlying mechanisms are briefly discussed in terms of the relationships of autaptic delay, synaptic delay, and inter-burst interval. These results show that synaptic and autaptic delays could contribute to each other and enhance synchronization transitions in the neuronal networks. This implies that autaptic and synaptic delays could play a vital role for the information transmission in neural systems.     

Delay- and coupling-induced firing patterns in oscillatory neural loops

For a feedforward loop of oscillatory Hodgkin-Huxley neurons interacting via excitatory chemical synapses, we show that a great variety of spatiotemporal periodic firing patterns can be encoded by properly chosen communication delays and synaptic weights, which contributes to the concept of temporal coding by spikes. These patterns can be obtained by a modulation of the multiple coexisting stable in-phase synchronized states or traveling waves propagating along or against the direction of coupling. We derive explicit conditions for the network parameters allowing us to achieve a desired pattern. Interestingly, whereas the delays directly affect the time differences between spikes of interacting neurons, the synaptic weights control the phase differences. Our results show that already such a simple neural circuit may unfold an impressive spike coding capability.     

Dynamic synchronization and chaos in an associative neural network with multiple active memories

Associative memory dynamics in neural networks are generally based on attractors. Retrieval based on fixed-point attractors works if only one memory pattern is retrieved at the time, but cannot enable the simultaneous retrieval of more than one pattern. Stable phase-locking of periodic oscillations or limit cycle attractors leads to incorrect feature bindings if the simultaneously retrieved patterns share some of their features. We investigate retrieval dynamics of multiple active patterns in a network of chaotic model neurons. Several memory patterns are kept simultaneously active and separated from each other by a dynamic itinerant synchronization between neurons. Neurons representing shared features alternate their synchronization between patterns, thus multiplexing their binding relationships. Our model includes a mechanism for self-organized readout or decoding of memory pattern coherence in terms of short-term potentiation and short-term depression of synaptic weights.     

Fast convergence of spike sequences to periodic patterns in recurrent networks

The dynamical attractors are thought to underlie many biological functions of recurrent neural networks. Here we show that stable periodic spike sequences with precise timings are the attractors of the spiking dynamics of recurrent neural networks with global inhibition. Almost all spike sequences converge within a finite number of transient spikes to these attractors. The convergence is fast, especially when the global inhibition is strong. These results support the possibility that precise spatiotemporal sequences of spikes are useful for information encoding and processing in biological neural networks.     

Network dilution and asymmetry in an efficient brain

ABSTRACT

The ultimate goal of neuroscience is to ultimately understand how the brain functions. The advancement of brain imaging shows us how the brain continuously alternates complex activity patterns and experimentally reveals how these patterns are responsible for memory, association, reasoning, and countless other tasks. Two fundamental parameters, dilution (the number of connections per node), and symmetry (the number of bidirectional connections of the same weight) characterise two fundamental features underlying the networks that connect the single neurons in the brain and generate these patterns. Mammalian brains show large variations of dilution, and mostly asymmetric connectivity, unfortunately the advantages which drove evolution to these state of network dilution and asymmetry are still unknown. Here, we studied the effects of symmetry and dilution on a discrete-time recurrent neural network with McCulloch–Pitts neurons. We use an exhaustive approach, in which we probe all possible inputs for several randomly connected neuron networks with different degrees of dilution and symmetry. We find an optimum value for the synaptic dilution and symmetry, which turns out to be in striking quantitative agreement with what previous researchers have found in the brain cortex, neocortex and hippocampus. The diluted asymmetric brain shows high memory capacity and pattern recognition speed, but most of all it is the less energy-consumptive with respect to fully connected and symmetric network topologies.     

动态突触、神经耦合与时间延迟对神经元发放的影响

神经元膜电位的受激发放在神经系统的信息传递中起着重要作用.基于一个受动态突触刺激的突触后神经元发放模型,采用数值模拟和傅里叶变换分析的方法研究了动态突触、神经耦合与时间延迟对突触后神经元发放的影响.结果发现:突触前神经元发放频率与Hodgkin-Huxley神经元的固有频率发生共振决定了突触后神经元发放的难易,特定频率范围内的电流刺激有利于神经元激发,动态突触输出的随机突触电流中这些电流刺激所占的比率在很大程度上影响了突触后神经元的发放次数;将突触后神经元换成神经网络后,网络中神经元之间的耦合可以促进神经元的发放,耦合中的时间延迟可以增强这种促进作用,但是不会改变神经耦合对神经元发放的促进模式.     

Gradient learning in spiking neural networks by dynamic perturbation of conductances

We present a method of estimating the gradient of an objective function with respect to the synaptic weights of a spiking neural network. The method works by measuring the fluctuations in the objective function in response to dynamic perturbation of the membrane conductances of the neurons. It is compatible with recurrent networks of conductance-based model neurons with dynamic synapses. The method can be interpreted as a biologically plausible synaptic learning rule, if the dynamic perturbations are generated by a special class of "empiric" synapses driven by random spike trains from an external source.     

Subcellular localization of the antidepressant-sensitive norepinephrine transporter

Background  

Reuptake of synaptic norepinephrine (NE) via the antidepressant-sensitive NE transporter (NET) supports efficient noradrenergic signaling and presynaptic NE homeostasis. Limited, and somewhat contradictory, information currently describes the axonal transport and localization of NET in neurons.     

Synaptic depression and short-term habituation are located in the sensory part of the mammalian startle pathway

Background  

Short-term habituation of the startle response represents an elementary form of learning in mammals. The underlying mechanism is located within the primary startle pathway, presumably at sensory synapses on giant neurons in the caudal pontine reticular nucleus (PnC). Short trains of action potentials in sensory afferent fibers induce depression of synaptic responses in PnC giant neurons, a phenomenon that has been proposed to be the cellular correlate for short-term habituation. We address here the question whether both this synaptic depression and the short-term habituation of the startle response are localized at the presynaptic terminals of sensory afferents. If this is confirmed, it would imply that these processes take place prior to multimodal signal integration, rather than occurring at postsynaptic sites on PnC giant neurons that directly drive motor neurons.     

Sensitization of spinal cord nociceptive neurons with a conjugate of substance P and cholera toxin

Background  

Several investigators have coupled toxins to neuropeptides for the purpose of lesioning specific neurons in the central nervous system. By producing deficits in function these toxin conjugates have yielded valuable information about the role of these cells. In an effort to specifically stimulate cells rather than kill them we have conjugated the neuropeptide substance P to the catalytic subunit of cholera toxin (SP-CTA). This conjugate should be taken up selectively by neurokinin receptor expressing neurons resulting in enhanced adenylate cyclase activity and neuronal firing.     

Structured information in sparse-code metric neural networks

Sparse-code networks have retrieval abilities which are strongly dependent on the firing threshold for the neurons. If the connections are spatially uniform, the macroscopic properties of the network can be measured by the overlap between neurons and learned patterns, and by the global activity. However, for nonuniform networks, for instance small-world networks, the neurons can retrieve fragments of patterns without performing global retrieval. Local overlaps are needed to describe the network. We characterize the structure type of the neural states using a parameter that is related to fluctuations of the local overlaps, with distinction between bump and block phases. Simulation of neural dynamics shows a competition between localized (bump), structured (block) and global retrieval. When the network topology randomness increases, the phase-diagram shows a transition from local to global retrieval. Furthermore, the local phase splits into a bump phase for low activity and a block phase for high activity. A theoretical approach solves the asymptotic limit of the model, and confirms the simulation results which predicts the change of stability from bumps to blocks when the storage ratio increases.     

变权小世界生物神经网络的兴奋及优化特性

根据实际生物神经网络具有小世界连接和神经元之间的连接强度随时间变化的特点,首先构造了一个以Hodgkin-Huxley方程为节点动力学模型的动态变权小世界生物神经网络模型,然后研究了该模型神经元的兴奋特性、权值变化特点和不同的学习系数对神经元的兴奋统计特性的影响.最有意义的结果是,在同样的网络结构、网络参数及外部刺激信号的条件下,学习系数b存在一个最优值b^*,使生物神经网络的兴奋度在b=b^*时达到最大. 关键词： 动态变权生物神经网络 小世界网络 Hodgkin-Huxley方程     

Imaging the neural circuitry and chemical control of aggressive motivation

Background  

With the advent of functional magnetic resonance imaging (fMRI) in awake animals it is possible to resolve patterns of neuronal activity across the entire brain with high spatial and temporal resolution. Synchronized changes in neuronal activity across multiple brain areas can be viewed as functional neuroanatomical circuits coordinating the thoughts, memories and emotions for particular behaviors. To this end, fMRI in conscious rats combined with 3D computational analysis was used to identifying the putative distributed neural circuit involved in aggressive motivation and how this circuit is affected by drugs that block aggressive behavior.     

A novel BDNF gene promoter directs expression to skeletal muscle

Background  

Cell-specific expression of the gene that encodes brain-derived neurotrophic factor (BDNF) is required for the normal development of peripheral sensory neurons and efficient synaptic transmission in the mature central and peripheral nervous system. The control of BDNF gene expression involves multiple tissue and cell-specific promoters that are differentially regulated. The molecular mechanisms that are responsible for tissue and cell-specific expression of these promoters are still incompletely understood.     

Dopamine presynaptically and heterogeneously modulates nucleus accumbens medium-spiny neuron GABA synapses in vitro

Background  

The striatal complex is the major target of dopamine action in the CNS. There, medium-spiny GABAergic neurons, which constitute about 95% of the neurons in the area, form a mutually inhibitory synaptic network that is modulated by dopamine. When put in culture, the neurons reestablish this network. In particular, they make autaptic connections that provide access to single, identified medium-spiny to medium-spiny neuron synaptic connections.     

Distinct roles of presynaptic dopamine receptors in the differential modulation of the intrinsic synapses of medium-spiny neurons in the nucleus accumbens

Background

In both schizophrenia and addiction, pathological changes in dopamine release appear to induce alterations in the circuitry of the nucleus accumbens that affect coordinated thought and motivation. Dopamine acts principally on medium-spiny GABA neurons, which comprise 95% of accumbens neurons and give rise to the majority of inhibitory synapses in the nucleus. To examine dopamine action at single medium-spiny neuron synapses, we imaged Ca²⁺ levels in their presynaptic varicosities in the acute brain slice using two-photon microscopy.

Results

Presynaptic Ca²⁺ rises were differentially modulated by dopamine. The D1/D5 selective agonist SKF81297 was exclusively facilitatory. The D2/D3 selective agonist quinpirole was predominantly inhibitory, but in some instances it was facilitatory. Studies using D2 and D3 receptor knockout mice revealed that quinpirole inhibition was either D2 or D3 receptor-mediated, while facilitation was mainly D3 receptor-mediated. Subsets of varicosities responded to both D1 and D2 agonists, showing that there was significant co-expression of these receptor families in single medium-spiny neurons. Neighboring presynaptic varicosities showed strikingly heterogeneous responses to DA agonists, suggesting that DA receptors may be differentially trafficked to individual varicosities on the same medium-spiny neuron axon.

Conclusion

Dopamine receptors are present on the presynaptic varicosities of medium-spiny neurons, where they potently control GABAergic synaptic transmission. While there is significant coexpression of D1 and D2 family dopamine receptors in individual neurons, at the subcellular level, these receptors appear to be heterogeneously distributed, potentially explaining the considerable controversy regarding dopamine action in the striatum, and in particular the degree of dopamine receptor segregation on these neurons. Assuming that post-receptor signaling is restricted to the microdomains of medium-spiny neuron varicosities, the heterogeneous distribution of dopamine receptors on individual varicosities is likely to encode patterns in striatal information processing.     

Hippocampal CA1/subiculum-prefrontal cortical pathways induce plastic changes of nociceptive responses in cingulate and prelimbic areas

Background  

Projections from hippocampal CA1-subiculum (CA1/SB) areas to the prefrontal cortex (PFC), which are involved in memory and learning processes, produce long term synaptic plasticity in PFC neurons. We examined modifying effects of these projections on nociceptive responses recorded in the prelimbic and cingulate areas of the PFC.