Gastric vagal afferent inputs reach the glycemia-sensitive neurons of lateral hypothalamic area in the rat

The lateral hypothalamic area (LHA) is one of the most important central areas in the regulation of feeding behavior[1]. The glycemia-sensitive neurons within the LHA sense the blood glucose level and subsequently trig-ger various visceral and somatic responses for maintaining the homeostasis of blood glucose concentration. Some electrophysiological studies have demonstrated that the gastric vagal afferent inputs could reach the LHA in the cat[2,3], but the studies did not reveal whether th…     

Purkinje neuron synchrony elicits time-locked spiking in the cerebellar nuclei

An unusual feature of the cerebellar cortex is that its output neurons, Purkinje cells, release GABA (γ-aminobutyric acid). Their high intrinsic firing rates (50?Hz) and extensive convergence predict that their target neurons in the cerebellar nuclei would be largely inhibited unless Purkinje cells pause their spiking, yet Purkinje and nuclear neuron firing rates do not always vary inversely. One indication of how these synapses transmit information is that populations of Purkinje neurons synchronize their spikes during cerebellar behaviours. If nuclear neurons respond to Purkinje synchrony, they may encode signals from subsets of inhibitory inputs. Here we show in weanling and adult mice that nuclear neurons transmit the timing of synchronous Purkinje afferent spikes, owing to modest Purkinje-to-nuclear convergence ratios (～40:1), fast inhibitory postsynaptic current kinetics (τ(decay) = 2.5?ms) and high intrinsic firing rates (～90?Hz). In vitro, dynamically clamped asynchronous inhibitory postsynaptic potentials mimicking Purkinje afferents suppress nuclear cell spiking, whereas synchronous inhibitory postsynaptic potentials entrain nuclear cell spiking. With partial synchrony, nuclear neurons time-lock their spikes to the synchronous subpopulation of inputs, even when only 2 out of 40 afferents synchronize. In vivo, nuclear neurons reliably phase-lock to regular trains of molecular layer stimulation. Thus, cerebellar nuclear neurons can preferentially relay the spike timing of synchronized Purkinje cells to downstream premotor areas.     

大鼠丘脑中央下核神经元对不同刺激的反应

目的：观察丘脑中央下核（Sm)神经元对伤害性机械刺激,手针和电针刺激的反应特性。方法：在麻醉大鼠,用玻璃微电极细胞外记录的方法,观察Sm神经元对上述刺激的反应。结果：大多数对手针刺激反应的神经元一般地也对伤害性皮肤或肌肉机械刺激发生反应,这些神经元也对电针刺激穴位发生反应,其反应随刺激强度、串长或重复次数的增加而加强,揭示针刺与伤害性机械刺激具有相同的属性。结论：Sm可能在针感形成及针刺兴奋细胞纤维产生的镇痛中起重要作用。     

刺激呈现率影响小鼠下丘神经元声反应特性

自由声场条件下,以强度为特征频率阈上5dBSPL、时程为40ms的短纯音为声刺激,记录了小鼠下丘神经元对不同呈现率（0．5～20Hz）的声刺激反应．结果显示,随呈现率的增高,绝大多数神经元（87．3％,103／118）的冲动发放数单调下降,少数（12．7％,15／118）神经元的冲动发放数呈非单调变化,冲动发放数与刺激呈现率之间有显著相关性．即使在低范围内改变呈现率也能显著影响多数神经元的声反应特性,其临界呈现率及最大呈现率低于3．3Hz的神经元分别超过70％（75．4％,89／118）和40％（44．9％,53／118）．此外,提高刺激呈现率,部分神经元（17．8％,21／118）的发放模式发生改变,主要是由紧张型或相位爆发型向相位型转变．可见,下丘神经元声反应特性与声刺激呈现率密切相关．     

家鸽桡神经和坐骨神经传入冲动在丘脑背外后核的会聚

在氨基甲酸乙酯麻醉的36只鸽上,记录和分析了丘脑背外后核对桡神经传入冲动发生反应的103个神经元的单位放电.神经元的诱发反应可分为六种类型.其中一部分单位还对刺激坐骨神经发生反应.不同前、后肢的同时传入可以在同一神经元上会聚并具有相互作用.丘脑背外后核的多种形式会聚可能是家鸽丘脑对四肢躯体感觉传入信息进行整合和加工的基础.     

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.     

Functional mapping of single spines in cortical neurons in vivo

The individual functional properties and spatial arrangement of afferent synaptic inputs on dendrites have a critical role in the processing of information by neurons in the mammalian brain. Although recent work has identified visually-evoked local dendritic calcium signals in the rodent visual cortex, sensory-evoked signalling on the level of dendritic spines, corresponding to individual afferent excitatory synapses, remains unexplored. Here we used a new variant of high-resolution two-photon imaging to detect sensory-evoked calcium transients in single dendritic spines of mouse cortical neurons in vivo. Calcium signals evoked by sound stimulation required the activation of NMDA (N-methyl-D-aspartate) receptors. Active spines are widely distributed on basal and apical dendrites and pure-tone stimulation at different frequencies revealed both narrowly and widely tuned spines. Notably, spines tuned for different frequencies were highly interspersed on the same dendrites: even neighbouring spines were mostly tuned to different frequencies. Thus, our results demonstrate that NMDA-receptor-dependent single-spine synaptic inputs to the same dendrite are highly heterogeneous. Furthermore, our study opens the way for in vivo mapping of functionally defined afferent sensory inputs with single-synapse resolution.     

Immediate and chronic changes in responses of somatosensory cortex in adult flying-fox after digit amputation

The somatosensory cortex of adult mammals has been shown to have a capacity to reorganize when inputs are removed by cutting afferent nerves or amputating a part of the body. The area of cortex that would normally respond to stimulation of the missing input can become responsive to inputs from other parts of the body surface. Although a few animals have been studied with repeat recording, no attempt has been made to follow the time-course of changes at cortical loci and the immediate effects of a small amputation have not been reported. We have followed the changes in response in the primary somatosensory cortex in the flying-fox following amputation of the single exposed digit on the forelimb. Immediately after amputation, neurons in the area of cortex receiving inputs from the missing digit were not silent but responded to stimulation of adjoining regions of the digit, hand, arm and wing. In the week following amputation, the enlarged receptive fields shrank until they covered only the skin around the amputation wound. The immediate response is interpreted as a removal of inhibition and the subsequent shrinking of the field may be due to re-establishment of the inhibitory balance in the affected cortex and its inputs.     

Histamine plays a part in induction of drinking by food intake

Drinking occurs around meal time in most mammals. Food-related drinking accounts for approximately 70% of daily fluid intake for rats, but little is known of the mechanisms by which eating elicits drinking. That eating and vagal stimulation elicit the release of histamine from gastric mucosa, together with the fact that drinking elicited by eating or exogenous histamine depends on an intact abdominal vagus, suggests a role for endogenous histamine as a component of food-related drinking in the rat. I report here that the combined antagonism of peripheral H1 and H2 receptors for histamine (1) attenuates drinking elicited by normal food-contingent stimulation of the gastrointestinal tract and (2) abolishes drinking elicited by pregastric food-contingent stimulation during sham feeding in the rat.     

Correlation between neural spike trains increases with firing rate

Populations of neurons in the retina, olfactory system, visual and somatosensory thalamus, and several cortical regions show temporal correlation between the discharge times of their action potentials (spike trains). Correlated firing has been linked to stimulus encoding, attention, stimulus discrimination, and motor behaviour. Nevertheless, the mechanisms underlying correlated spiking are poorly understood, and its coding implications are still debated. It is not clear, for instance, whether correlations between the discharges of two neurons are determined solely by the correlation between their afferent currents, or whether they also depend on the mean and variance of the input. We addressed this question by computing the spike train correlation coefficient of unconnected pairs of in vitro cortical neurons receiving correlated inputs. Notably, even when the input correlation remained fixed, the spike train output correlation increased with the firing rate, but was largely independent of spike train variability. With a combination of analytical techniques and numerical simulations using 'integrate-and-fire' neuron models we show that this relationship between output correlation and firing rate is robust to input heterogeneities. Finally, this overlooked relationship is replicated by a standard threshold-linear model, demonstrating the universality of the result. This connection between the rate and correlation of spiking activity links two fundamental features of the neural code.     

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.     

鸽上纹状体神经元对桡神经和坐骨神经传入冲动的反应

在61只家鸽上纹状体中,用玻璃微电极共记录到138个对电刺激桡神经和坐骨神经发生反应的单位.根据诱发反应放电型式,可分为三类:①单个或短串放电反应.②长串放电反应.③抑制性反应.其中①类细胞有116个.上纹状体神经元对躯体神经刺激反应的潜伏期差异较大,多数桡神经传入的诱发反应具有长潜伏期特征.结合解剖学资料对潜伏期差异的原因进行了讨论.认为,短潜伏期反应可能是由DIVA-Wulst通路直接传入引起,长潜伏期反应可能是经DLP-NI/NC-Wulst通路间接传入引起.     

Sustained firing in auditory cortex evoked by preferred stimuli

It has been well documented that neurons in the auditory cortex of anaesthetized animals generally display transient responses to acoustic stimulation, and typically respond to a brief stimulus with one or fewer action potentials. The number of action potentials evoked by each stimulus usually does not increase with increasing stimulus duration. Such observations have long puzzled researchers across disciplines and raised serious questions regarding the role of the auditory cortex in encoding ongoing acoustic signals. Contrary to these long-held views, here we show that single neurons in both primary (area A1) and lateral belt areas of the auditory cortex of awake marmoset monkeys (Callithrix jacchus) are capable of firing in a sustained manner over a prolonged period of time, especially when they are driven by their preferred stimuli. In contrast, responses become more transient or phasic when auditory cortex neurons respond to non-preferred stimuli. These findings suggest that when the auditory cortex is stimulated by a sound, a particular population of neurons fire maximally throughout the duration of the sound. Responses of other, less optimally driven neurons fade away quickly after stimulus onset. This results in a selective representation of the sound across both neuronal population and time.     

不同时程的前掩蔽声对小鼠下丘神经元声反应的掩蔽效应

自由声场条件下,以强度为神经元最佳频率阈上5dB,时程分别为40、60、80和100ms的纯音作为前掩蔽声,观察和记录了不同时程掩蔽声对小鼠(MusmusculusKm)下丘神经元发放和声强处理的影响.结果发现:随掩蔽声时程的增加,神经元发放抑制率逐渐增大(P<0.0001,n=41),反应潜伏期延长(P<0.01,n=41);其中受掩蔽声抑制的41个神经元中,绝大部分的(90.2%,37/41)反应动力学范围随掩蔽声时程的增加而逐渐变窄(P<0.0001),另有4个神经元的反应动力学范围则出现增加(9.8%,4/41).推测前掩蔽声的时程效应与掩蔽声激活的抑制性输入强度以及持续时间相关.     

电场作用下海马锥体神经元等效应建模

为解决电磁刺激治疗癫痫神经疾病的有效性和安全性等问题,建立了容易引起癫痫发作的海马CA3区锥体神经元在外电场刺激下的等效应模型,并通过Matlab 数值仿真,分别研究了其在直流和交流外电场作用下的动力学特性。仿真结果表明,神经元的放电频率受到直流电场强度的调制,特别对电场的方向比较敏感。当电场为负向时,电场强度的变化对神经元的动力学特性影响明显,当电场为正向时,影响不明显;在交流电场刺激下,神经元的动力学特性改变具有外部电场频率依赖性,不同频率刺激下神经元会出现周期簇放电、同步放电、周期峰放电和混沌放电等状态。据此可指导医生制定更为有效安全的神经疾病电磁刺激治理方案。     

A study on discharge features of interneuron in the hippocampal network

The firing of neurons in the hippocampal network has a close relationship with human memory and learning. In this paper, a numerical simulation of interneurons in the hippocampal network has been operated. It analyzes the influence of external stimulation on firing rhythms. The diversity of firing pattern, especially the circle of unit firing pattern, is shown by ISI.     

Neuron-type-specific signals for reward and punishment in the ventral tegmental area

Dopamine has a central role in motivation and reward. Dopaminergic neurons in the ventral tegmental area (VTA) signal the discrepancy between expected and actual rewards (that is, reward prediction error), but how they compute such signals is unknown. We recorded the activity of VTA neurons while mice associated different odour cues with appetitive and aversive outcomes. We found three types of neuron based on responses to odours and outcomes: approximately half of the neurons (type I, 52%) showed phasic excitation after reward-predicting odours and rewards in a manner consistent with reward prediction error coding; the other half of neurons showed persistent activity during the delay between odour and outcome that was modulated positively (type II, 31%) or negatively (type III, 18%) by the value of outcomes. Whereas the activity of type I neurons was sensitive to actual outcomes (that is, when the reward was delivered as expected compared to when it was unexpectedly omitted), the activity of type II and type III neurons was determined predominantly by reward-predicting odours. We 'tagged' dopaminergic and GABAergic neurons with the light-sensitive protein channelrhodopsin-2 and identified them based on their responses to optical stimulation while recording. All identified dopaminergic neurons were of type I and all GABAergic neurons were of type II. These results show that VTA GABAergic neurons signal expected reward, a key variable for dopaminergic neurons to calculate reward prediction error.     

Dynamic receptive field plasticity in rat spinal cord dorsal horn following C-primary afferent input

The central terminals of cutaneous primary afferent neurons are spatially ordered in the dorsal horn in a highly organized fashion such that a point-to-point map represents the body surface. This afferent terminal somatotopic map correlates with the map of the receptive fields of the cells on which they terminate. The location, size and modality of the cutaneous receptive fields of dorsal horn neurons necessarily depend upon the anatomical presence of afferent nerve fibres which deliver information from the periphery, directly or indirectly, to the cells. However the receptive field size and modality of a cell do not depend only on anatomical connections. Excitatory and inhibitory interneurons, descending influences and facilitations or depressions of synaptic contacts can alter receptive field properties. Here we show that prolonged and substantial cutaneous receptive field changes can be produced by brief inputs from peripheral unmyelinated afferent fibres.     

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.     

Sensory transmitters regulate intracellular calcium in dorsal horn neurons

Primary afferent terminals in the dorsal horn of the spinal cord release excitatory amino acid and peptide transmitters that initiate the central processing of nociceptive information. The postsynaptic actions of amino acid transmitters on spinal neurons have been well characterized, but the cellular basis of peptide actions remains unclear. Substance P is the best characterized of the peptides present in sensory neurons and has been shown to depolarize dorsal horn neurons and to facilitate nociceptive reflexes. To determine the mechanisms by which substance P contributes to afferent synaptic transmission, we have monitored the levels of intracellular calcium in single isolated rat dorsal horn neurons and report that substance P can produce a prolonged elevation in calcium concentration by mobilizing its release from intracellular stores. This elevation may contribute to the long-term changes in the excitable properties of dorsal horn neurons that occur following afferent fibre stimulation. We have also found that L-glutamate elevates intracellular calcium in substance P-sensitive dorsal horn neurons by increasing calcium influx. These results provide a direct demonstration of intracellular calcium changes in response to neuropeptides in mammalian central neurons. They also indicate that there is convergent regulation of intracellular calcium in dorsal horn neurons by two different classes of sensory transmitters that are co-released from the same afferent terminals.