Feedback Inhibition and Throughput Properties of an Integrate-and-Fire-or-Burst Network Model of Retinogeniculate Transmission

Computational modeling has played an important role in the dissection of the biophysical basis of rhythmic oscillations in thalamus that are associated with sleep and certain forms of epilepsy. In contrast, the dynamic filter properties of thalamic relay nuclei during states of arousal are not well understood. Here we present a modeling and simulation study of the throughput properties of the visually driven dorsal lateral geniculate nucleus (dLGN) in the presence of feedback inhibition from the perigeniculate nucleus (PGN). We employ thalamocortical (TC) and thalamic reticular (RE) versions of a minimal integrate-and-fire-or-burst type model and a one-dimensional, two-layered network architecture. Potassium leakage conductances control the neuromodulatory state of the network and eliminate rhythmic bursting in the presence of spontaneous input (i.e., wake up the network). The aroused dLGN/PGN network model is subsequently stimulated by spatially homogeneous spontaneous retinal input or spatio-temporally patterned input consistent with the activity of X-type retinal ganglion cells during full-field or drifting grating visual stimulation. The throughput properties of this visually-driven dLGN/PGN network model are characterized and quantified as a function of stimulus parameters such as contrast, temporal frequency, and spatial frequency. During low-frequency oscillatory full-field stimulation, feedback inhibition from RE neurons often leads to TC neuron burst responses, while at high frequency tonic responses dominate. Depending on the average rate of stimulation, contrast level, and temporal frequency of modulation, the TC and RE cell bursts may or may not be phase-locked to the visual stimulus. During drifting-grating stimulation, phase-locked bursts often occur for sufficiently high contrast so long as the spatial period of the grating is not small compared to the synaptic footprint length, i.e., the spatial scale of the network connectivity.     

A Possible Mechanism of Blocking of Limbic Motor Seizure Reactions Induced by Activation of the Thalamic Reticular Nucleus

Experiments were directed toward elucidation of the role of the thalamic reticular nucleus (R) in the modulation of generalized seizure reactions under kindling conditions and of the mechanisms mediating the effects of stimulation of the above nucleus on seizure activity. It was shown that activation of the thalamic R in rats limits generalization of the seizure reactions both in the course of development of seizures of limbic genesis (evoked by stimulation of the hippocampus) and under conditions of the existence of a pre-formed epileptic nidus. Tetanic stimulation of the R in cats under conditions of acute experiments induced significant facilitation of IPSPs in thalamo-cortical neurons of the ventrolateral thalamic nucleus. This effect is rather long-lasting and may be considered a mechanism providing blocking of generalized seizures under kindling conditions. Neirofiziologiya/Neurophysiology, Vol. 37, No. 4, pp. 352–361, July–August, 2005.     

Augmented Reticular Thalamic Bursting and Seizures in Scn1a-Dravet Syndrome

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Thalamic control of sensory processing and spindles in a biophysical somatosensory thalamoreticular circuit model of wakefulness and sleep

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A multivariate population density model of the dLGN/PGN relay

Using a population density approach we study the dynamics of two interacting collections of integrate-and-fire-or-burst (IFB) neurons representing thalamocortical (TC) cells from the dorsal lateral geniculate nucleus (dLGN) and thalamic reticular (RE) cells from the perigeniculate nucleus (PGN). Each population of neurons is described by a multivariate probability density function that satisfies a conservation equation with appropriately defined probability fluxes and boundary conditions. The state variables of each neuron are the membrane potential and the inactivation gating variable of the low-threshold Ca²⁺ current I_T. The synaptic coupling of the populations and external excitatory drive are modeled by instantaneous jumps in the membrane potential of postsynaptic neurons. The population density model is validated by comparing its response to time-varying retinal input to Monte Carlo simulations of the corresponding IFB network composed of 100 to 1000 cells per population. In the absence of retinal input, the population density model exhibits rhythmic bursting similar to the 7 to 14 Hz oscillations associated with slow wave sleep that require feedback inhibition from RE to TC cells. When the TC and RE cell potassium leakage conductances are adjusted to represent cholingergic neuromodulation and arousal of the network, rhythmic bursting of the probability density model may either persists or be eliminated depending on the number of excitatory (TC to RE) or inhibitory (RE to TC) connections made by each presynaptic cell. When the probability density model is stimulated with constant retinal input (10–100 spikes/sec), a wide range of responses are observed depending on cellular parameters and network connectivity. These include asynchronous burst and tonic spikes, sleep spindle-like rhythmic bursting, and oscillations in population firing rate that are distinguishable from sleep spindles due to their amplitude, frequency, or the presence of tonic spikes. In this context of dLGN/PGN network modeling, we find the population density approach using 2,500 mesh points and resolving membrane voltage to 0.7 mV is over 30 times more efficient than 1000-cell Monte Carlo simulations. Action Editor: David Golomb     

家兔外膝体神经元回路的研究

家兔的视觉系统有其特色,其外膝体的解剖和生理特性与猫的情况有所不同。本文综述了家兔外膝体神经元回路研究的进展,特别是关于返回抑制回路的组成和机能意义为研究进展,并以此为例说明丘脑-大脑皮层的复杂相关关系。     

Functional convergence of on-off direction-selective ganglion cells in the visual thalamus

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Localized Bumps of Activity Sustained by Inhibition in a Two-Layer Thalamic Network

Based on head direction experiments in rats, the existence of localized bumps of thalamic activity has been proposed. We computationally demonstrate the existence of a novel class of localized bump solutions in a two-layer conductance-based thalamic network and analyze the mechanisms behind these stable patterns. In contrast to previous models of bump activity, here inhibition plays a crucial role in initially spreading neuronal firing and in subsequently sustaining it. In our model, we incorporate local strong, fast GABA(A) inhibition and diffuse weak, slow GABA(B) inhibition, based on previous biophysical experiments. These forms of inhibition contribute in different, yet complementary, ways to the observed pattern formation.     

双眼和单眼视觉剥夺猫外膝体细胞的图形适应

为测定丘脑外膝体细胞的图形适应是否依赖于早期视觉经验,在细胞外记录了双眼和单眼缝合的猫外膝体中断细胞对手工时间运动光栅刺激的反应。在双眼剥夺猫,占６８％的记录到的细胞在３０ｓ内反应下降到稳定值,其平均反应值下降３３％,适应程度较正常猫显著。在单眼剥夺猫,记录到的剥夺眼驱动的和非剥夺眼驱动的细胞中,分别有占５３％和４４％的细胞显示图形适应,两者差别不大。研究表明,早期视剥夺能增强或保持图形适应,提示     

Impaired clustered protocadherin‐α leads to aggregated retinogeniculate terminals and impaired visual acuity in mice

Clustered protocadherins (cPcdhs) comprising cPcdh‐α, ‐β, and ‐γ, encode a large family of cadherin‐like cell‐adhesion molecules specific to neurons. Impairment of cPcdh‐α results in abnormal neuronal projection patterns in specific brain areas. To elucidate the role of cPcdh‐α in retinogeniculate projections, we investigated the morphological patterns of retinogeniculate terminals in the lateral geniculate (LG) nucleus of mice with impaired cPcdh‐α. We found huge aggregated retinogeniculate terminals in the dorsal LG nucleus, whereas no such aggregated terminals derived from the retina were observed in the olivary pretectal nucleus and the ventral LG nucleus. These aggregated terminals appeared between P10 and P14, just before eye opening and at the beginning of the refinement stage of the retinogeniculate projections. Reduced visual acuity was observed in adult mice with impaired cPcdh‐α, whereas the orientation selectivity and direction selectivity of neurons in the primary visual cortex were apparently normal. These findings suggest that cPcdh‐α is required for adequate spacing of retinogeniculate projections, which may be essential for normal development of visual acuity.

     

刺激兔杏仁体影响内膝体听觉神经元的ON-OFF反应

在２３只三碘季铵酚麻痹的新西兰兔上记录细胞外放电,观察短纯音诱发的内膝体神经元ｏｎｏｆ反应的特性及电刺激边缘系统杏仁外侧核（Ｌａｔｅｒａｌａｍｙｇｄａｌｏｉｄｎｕｃｌｅｕｓ,ＬＡｍ）对反应的影响。实验发现,内膝体神经元的ｏｎｏｆ反应与纯音刺激的强度、频率及作用时程有关;刺激ＬＡｍ,可以抑制ｏｎｏｆ反应,或是使ｏｎｏｆ反应放电构型发生变化。ｏｎｏｆ反应是神经元对声音信号作用时程及声音的起止进行编码的方式之一,ＬＡｍ对ｏｎｏｆ反应的影响表明,边缘系统杏仁体的活动可以调控听觉中枢对声音时间信息的编码。     

Modification of a Colliculo-thalamocortical Mouse Brain Slice,Incorporating 3-D printing of Chamber Components and Multi-scale Optical Imaging

The ability of the brain to process sensory information relies on both ascending and descending sets of projections. Until recently, the only way to study these two systems and how they interact has been with the use of in vivo preparations. Major advances have been made with acute brain slices containing the thalamocortical and cortico-thalamic pathways in the somatosensory, visual, and auditory systems. With key refinements to our recent modification of the auditory thalamocortical slice¹, we are able to more reliably capture the projections between most of the major auditory midbrain and forebrain structures: the inferior colliculus (IC), medial geniculate body (MGB), thalamic reticular nucleus (TRN), and the auditory cortex (AC). With portions of all these connections retained, we are able to answer detailed questions that complement the questions that can be answered with in vivo preparations. The use of flavoprotein autofluorescence imaging enables us to rapidly assess connectivity in any given slice and guide the ensuing experiment. Using this slice in conjunction with recording and imaging techniques, we are now better equipped to understand how information processing occurs at each point in the auditory forebrain as information ascends to the cortex, and the impact of descending cortical modulation. 3-D printing to build slice chamber components permits double-sided perfusion and broad access to networks within the slice and maintains the widespread connections key to fully utilizing this preparation.     

Cell death and the creation of regional differences in neuronal numbers

Regional variations in cell death are ubiquitous in the nervous system. In the retina, cell death in retinal ganglion cells is elevated in the retinal periphery and may be important in setting up the initial conditions that produce central retinal specializations such as an area centralis or visual streak. In central visual system structures, pronounced spatial and spatiotemporal inhomogeneities in cell death are seen both in layers and regions of the lateral geniculate nucleus and superior colliculus; similar indications of inhomogeneities are seen in those nonvisual structures that have been examined. Cell death in the cortex is highly nonuniform, by layer and by cortical area. A variety of possible functions for these regional losses are proposed, in the context of a uniform mechanism for cell death that allows it to assume multiple functions. © 1992 John Wiley & Sons, Inc.     

Retinal Inputs to the Thalamus Are Selectively Gated by Arousal

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Isocortical Hyperemia and Allocortical Inflammation and Atrophy Following Generalized Convulsive Seizures of Thalamic Origin in the Rat

1. Generalized convulsive seizures can be elicited by a single unilateral microinjection of the cholinergic muscarinic agonist, carbachol, into the specific sites of the thalamus including ventral posterolateral and the reticular thalamic nuclei. The implication of the thalamic specific and reticular neurons is reviewed and discussed.2. On the basis of the c-fos regional expression and well-known efferent and afferent pathways linking these regions, a neuronal network relating the limbic, thalamo–striatal–cortical, and central autonomic systems, was constructed.3. The pattern of Fos immunoreactivity associated with long-lasting isocortical vasodilatation elicited by generalized convulsive seizures in anesthetized rat following cholinergic stimulation of the thalamus can be attributed to both the electrocortical activity and the long-lasting increase in cortical blood flow. We propose that the sustained cerebral cortical blood flow response during convulsive epileptic seizures may implicate intracerebral vasodilatory and vasoconstrictory neural mechanisms. Double-labeled NADPH-d and Fos-positive neurons implicated in maintaining the sustained isocortical vasodilatory response were found in the anterior lateral hypothalamic area. Inhibition of these neurons prevented the increase in cortical blood flow despite an increased metabolic demand manifested by the ictal electrocortical activity.4. Medial temporal lobe atrophy, including hippocampus, amygdala, and parahippocampal gyrus (piriform and entorhinal cortices) are the most common pathology in man. However the origin of medial lobe atrophy remain uncertain. Our results provide evidence that the allocortical microvascular inflammation may be in origin of the neurovascular degenerative processes leading to atrophy.     

Noise-Induced Coherence and Network Oscillations in a Reduced Bursting Model

The dynamics of the Hindmarsh-Rose (HR) model of bursting thalamic neurons is reduced to a system of two linear differential equations that retains the subthreshold resonance properties of the HR model. Introducing a reset mechanism after a threshold crossing, we turn this system into a resonant integrate-and-fire (RIF) model. Using Monte-Carlo simulations and mathematical analysis, we examine the effects of noise and the subthreshold dynamic properties of the RIF model on the occurrence of coherence resonance (CR). Synchronized burst firing occurs in a network of such model neurons with excitatory pulse-coupling. The coherence level of the network oscillations shows a stochastic resonance-like dependence on the noise level. Stochastic analysis of the equations shows that the slow recovery from the spike-induced inhibition is crucial in determining the frequencies of the CR and the subthreshold resonance in the original HR model. In this particular type of CR, the oscillation frequency strongly depends on the intrinsic time scales but changes little with the noise intensity. We give analytical quantities to describe this CR mechanism and illustrate its influence on the emerging network oscillations. We discuss the profound physiological roles this kind of CR may have in information processing in neurons possessing a subthreshold resonant frequency and in generating synchronized network oscillations with a frequency that is determined by intrinsic properties of the neurons. PACS 05.45.-a, 05.40.Ca, 87.18.Sn, 87.19     

Kinetics of low threshold calcium channels of relay cells in cat lateral geniculate nucleus

Kinetics of the low threshold T-type Ca2+ channel is studied with single electrode voltage damp technique on brain slices of the cat lateral geniculate nucleus (LGN). Space damp is dramatically improved by blocking various K+ and Na+ channels, decreasing Ca2+ current and selecting proper holding potentials. Results from this study are similar to those obtained from acutely dissociated LGN neurons of the rat, indicating that the kinetics of T-Ca2+ channels of the cat LGN neurons is the same as that of the rat LGN. The result reported previously on the cat LGN may result from a defect in space damp.     

树鼩在医学生物学中的应用

目的树鼩是一种新型实验动物,由于它的许多分子与细胞结构近似于人类,已成功建立了多种人类病毒感染的动物模型,并在神经生物学、生殖生物学、免疫学和社会心理学等方面有相当广泛和深入的应用和研究。