老年猫视皮层细胞对刺激反应的对比敏感度下降伴随皮层内抑制作用减弱(英文)

对人类和动物的心理学研究证实,老年个体的视觉对比敏感度相对青年个体显著下降。为揭示其可能的神经机制,采用在体细胞外单细胞记录技术研究青、老年猫(Felis catus)初级视皮层(primary visual cortex,V1)细胞对不同视觉刺激对比度的调谐反应。结果显示,老年猫V1细胞对视觉刺激反应的平均对比敏感度比青年猫显著下降,这与灵长类报道的研究结果相一致,表明衰老影响视皮层细胞对视觉刺激反应的对比敏感度是灵长类和非灵长类哺乳动物中普遍存在的现象,并可能是介导老年性视觉对比敏感度下降的神经基础。另外,与青年猫相比,老年猫初级视皮层细胞对视觉刺激的反应性显著增强,信噪比下降,感受野显著增大,表明衰老导致的初级视皮层细胞对视觉刺激反应的对比敏感度下降伴随着皮层内抑制性作用减弱。     

Top-Down Inputs Enhance Orientation Selectivity in Neurons of the Primary Visual Cortex during Perceptual Learning

Perceptual learning has been used to probe the mechanisms of cortical plasticity in the adult brain. Feedback projections are ubiquitous in the cortex, but little is known about their role in cortical plasticity. Here we explore the hypothesis that learning visual orientation discrimination involves learning-dependent plasticity of top-down feedback inputs from higher cortical areas, serving a different function from plasticity due to changes in recurrent connections within a cortical area. In a Hodgkin-Huxley-based spiking neural network model of visual cortex, we show that modulation of feedback inputs to V1 from higher cortical areas results in shunting inhibition in V1 neurons, which changes the response properties of V1 neurons. The orientation selectivity of V1 neurons is enhanced without changing orientation preference, preserving the topographic organizations in V1. These results provide new insights to the mechanisms of plasticity in the adult brain, reconciling apparently inconsistent experiments and providing a new hypothesis for a functional role of the feedback connections.     

猫丘系层Glu与GABA表达的年龄相关性变化

为探讨青年猫和老年猫丘系层谷氨酸（Glu）与γ-氨基丁酸（GABA）表达的年龄相关性变化,利用Nissl染色显示丘系层神经元,免疫组织化学ABC法标记Glu和GABA免疫阳性神经元。光镜下观察、拍照,对Glu和GABA能免疫阳性神经元分别计数并换算成密度。利用IPE软件测量Glu和GABA免疫阳性反应灰度值（免疫阳性强度与灰度值成反比）。结果显示,Glu和GABA阳性反应神经元、阳性纤维及其终末在青年猫及老年猫丘系层均有分布。与青年猫相比,老年猫丘系层Glu能免疫阳性神经元密度显著增大（p〈0.01）,免疫阳性反应灰度值显著降低（p〈0.01）,免疫阳性反应显著增强;GABA能免疫阳性神经元密度显著下降（p〈0.01）,免疫阳性反应灰度值显著升高（p〈0.01）,免疫阳性反应显著减弱。结果提示,衰老过程中猫丘系层Glu的表达增强和GABA的表达减弱导致兴奋性神经递质和抑制性神经递质之间的平衡失调,可能是视觉、听觉、躯体感觉等单感觉功能衰退及多感觉整合功能增强的主要原因之一。     

急性毁损猫的初级视区使高级视区细胞失去对视觉刺激的诱发反应(英文)

心理物理学研究提示,初级视区毁损后的视觉残留可能是通过外纹状皮层的神经网络重组介导的,但缺少支持这一假说的电生理实验证据。采用在体细胞外单细胞记录技术,该研究分别检测了初级视区(主要包括17和18区)急性毁损猫和正常对照猫的高级视区(包括19、20和21区)神经元对不同视觉刺激的反应性。结果显示,与对照相比,急性毁损初级视区使99.3%的高级视区神经元丧失对运动光栅刺激的诱发反应,93%的神经元丧失对闪光刺激的反应。该结果表明,急性毁损成年猫的初级视皮层可能会导致其绝大部分视觉能力丧失。在幼年期实施初级视皮层毁损后,成年猫出现的残留视觉可能主要是由于手术后皮层下神经核团与外纹状皮层之间的通路重组引起的。     

猫外侧膝状体年龄相关性形态学变化

目的比较青年猫与老年猫外侧膝状体(lateral geniculate nucleus,LGN)神经元及γ-氨基丁酸(gama-aminobutyric acid,GABA)能神经元的年龄相关性变化,探讨老年个体视觉功能衰退的相关神经机理。方法Nissl染色示猫外侧膝状体分层结构(A、A1、C3层)及神经元,免疫组织化学法示GABA免疫阳性神经元。光镜下观察、拍照,Nissl染色切片测量外侧膝状体各层厚度、神经元胞体直径并计数神经元数量;免疫组化染色切片测量外侧膝状体各层中GABA阳性神经元胞体直径并计数GABA阳性神经元数量。结果青年猫及老年猫外侧膝状体各层厚度、神经元数量及胞体直径无明显改变(P>0.05);与青年猫相比,老年猫外侧膝状体各层中GABA阳性神经元数量及胞体直径均有不同程度的显著下降(P<0.01),且GABA免疫阳性反应减弱。结论在动物个体衰老进程中,外侧膝状体总体神经元保持相对稳定可能对老年个体维持视觉功能具有一定意义;老年个体外侧膝状体GABA能神经元对视觉信息传递及整合过程的抑制性调节功能削弱,可能是外侧膝状体水平上导致老年个体视觉功能衰退的原因之一。     

The tuning of striate neurons to cross-like figures during local blockade of intracortical inhibition]

Many neurons in the cat primary visual cortex reveal sensitivity to cruciform and corner figures as well as to local orientation discontinuities. We investigated this sensitivity in 85 V1 neurons before and after the local blockade of GABA(A)ergic inhibition by microiontophoretic application of bicuculline and observed two opposite effects: a decrease or disappearance of sensitivity to crosses in about half of the neurons and its increase or appearance in about one third of the units. The results indicate substantial and drastically different contribution of intracortical inhibition to sensitivity to line-crossings in the visual cortical neurons. Some possible mechanisms of this difference are discussed.     

猫初级视皮层内GIu/GABA表达比率的衰老性变化

最近的一些研究结果显示,视皮层内抑制性递质系统作用减弱可能是导致老年性视觉功能衰退的重要因素.是否皮层内兴奋性递质系统亦伴随衰老而发牛改变并影响皮层内神经兴奋与抑制的平衡尚不清楚.为此,利用Nissl染色和免疫组织化学染色方法以及Image-Pro Express图像分析软件对青、老年猫初级视皮层(17区)内各层神经元密度、兴奋性递质谷氨酸免疫反应阳性(Glu-immunoreactive,Glu-IR)神经元密度以及抑制性递质γ-氨基丁酸免疫反应阳性(γ-aminobutyric acid.immunoreactive,GABA-IR)神经元密度进行了统汁分析.结果显示,青、老年猫初级视皮层各层神经元密度均没有明显的年龄性差异(P>0.05);与青年猫相比,老年猫初级视皮层Glu-IR、GABA-IR神经元密度均显著减少(P<0.01),而Glu.IR/GABA.IR神经元密度比率去却显著增大(P<0.01).结果提示,老年猫初级视皮层内兴奋性递质系统作用相对增强,而抑制性递质系统的作用相对减弱,导致皮层内兴奋-抑制平衡关系失调,这可能是引起老年个体视觉功能衰退的重要原因之一.     

GABA antagonism reverses hypoxic respiratory depression in the cat

We assessed the role of gamma-aminobutyric acid (GABA) as a potential causative agent of hypoxic respiratory depression by monitoring the response of the phrenic neurogram to systemic infusion of the GABA antagonist bicuculline (0.01 mg.kg-1.min-1) under control conditions and during isocapnic brain hypoxia produced by CO inhalation in separate groups of anesthetized, glomectomized, vagotomized, paralyzed, and ventilated cats with blood pressure held constant. The maximum effect of bicuculline in subseizure doses in control cats was to increase minute phrenic activity to 151 +/- 14% of preinfusion values. Infusion was continued until seizure activity was seen in the electroencephalogram. A 53% decrease of arterial O2 content resulted in a marked reduction of both peak phrenic amplitude and phrenic firing frequency to 16 and 64% of control values, respectively. Infusion of bicuculline while the level of hypoxia was maintained constant restored both peak phrenic amplitude and phrenic firing frequency to prehypoxic levels. The maximum effect of bicuculline was to increase minute phrenic activity to 123 +/- 13% of the prehypoxic value. These results suggest that although GABA has only a modest role in determining the output of the control phrenic neurogram, a significant portion of the phrenic depression that occurs during hypoxia can be attributed to inhibition of respiratory neurons by GABA.     

Membrane potential synchrony in primary visual cortex during sensory stimulation

When the primary visual cortex (V1) is activated by sensory stimulation, what is the temporal correlation between the synaptic inputs to nearby neurons? This question underlies the origin of correlated activity, the mechanism of how visually evoked activity emerges and propagates in cortical circuits, and the relationship between spontaneous and evoked activity. Here, we have recorded membrane potential from pairs of V1 neurons in anesthetized cats and found that visual stimulation suppressed low-frequency membrane potential synchrony (0-10 Hz), and often increased synchrony at high frequencies (20-80 Hz). The increase in high-frequency synchrony occurred for neurons with similar orientation preferences and for neurons with different orientation preferences and occurred for a wide range of stimulus orientations. Thus, while only a subset of neurons spike in response to visual stimulation, a far larger proportion of the circuit is correlated with spiking activity through subthreshold, high-frequency synchronous activity that crosses functional domains.     

TrkB受体依赖的PV神经元调控小鼠视觉方位辨别能力的机制

神经营养因子-酪氨酸受体激酶B （tyrosine receptor kinase B,TrkB）信号通路在调控初级视皮层（primary visual cortex,V1）兴奋与抑制平衡上发挥着重要的作用,以往的研究揭示了其通过增加兴奋性传递效率来调控皮层兴奋性水平的机制,却并未阐明TrkB受体如何通过抑制系统来调控兴奋与抑制平衡,进而影响视觉皮层功能。为了探讨TrkB信号通路如何特异性地调控最主要的抑制性神经元——PV神经元进而对小鼠视觉皮层功能产生影响,本研究通过病毒特异性地降低V1区的PV神经元上TrkB受体的表达水平,并通过在体多通道电生理手段记录初级视皮层抑制性与兴奋性神经元功能变化,通过行为学实验测试小鼠的方位辨别能力改变。结果表明,初级视觉皮层中的PV抑制性神经元上的TrkB受体表达减少会显著增加兴奋性神经元的反应强度,减弱抑制性神经元与兴奋性神经元的方位辨别能力,增加二者的信噪比,但是小鼠个体水平的方位辨别能力出现下降。这些结果说明,TrkB信号通路并非单纯通过增加靶向PV神经元的兴奋性传递来调控PV神经元的功能,其对神经元信噪比的影响也并非由于抑制系统的增强所致。     

Responses of parietal associative neurons to stimulation of primary sensory areas

Responses of 251 neurons in the anterior part of the middle suprasylvian gyrus to stimulation of primary sensory (auditory, visual, somatosensory) areas and also to acoustic, visual, and somatosensory stimuli were studied in acute experiments on cats anesthetized with chloralose (40 mg/kg) and pentobarbital (20 mg/kg). Three groups of neurons were distinguished by their responses to stimulation of the primary sensory areas: those responding by an increased firing rate (117) or by inhibition (35) and those not responding (99). Responses of 193 neurons to stimulation of the peripheral afferent systems were analyzed. Neurons of the parietal associative cortex responded more frequently to cortical stimulation than to peripheral. By the duration of the latent period of their response to cortical stimulation the neurons were divided into three groups: those with short (less than 20 msec), medium (20–30 msec), and long latent periods (over 30 msec). The first group was the largest.Kemerovo State Medical Institute. Translated from Neirofiziologiya, Vol. 4, No. 5, pp. 524–530, September–October, 1972.     

Possible involvement of GABA in the central actions of benzodiazepines.

The effects of several benzodiazepines on a variety of nervous activities known or presumed to depend on GABA are presented and compared with those of agents that deplete or increase the level of endogenous GABA: antagonism of various convulsant agents in mice, enhancement of presynaptic inhibition in the spinal cord and the cuneate nucleus of cats, decrease of the spontaneous firing rate of cerebellar Purkinje cells in cats and rats, antagonism of bicuculine-induced depression of the strio-nigral-evoked potential in the cat, potentiation of haloperidol-induced catalepsy in rats, GABA-mimetic actions on drug-induced PGO-waves in cats and on eserine-induced circling in guinea pigs. Diazepam slightly increased the GABA level in the cat spinal cord and in the total brain of mice and rats; this increase does not seem to be due to an increase of GABA synthesis. It is concluded that benzodiazepines probably enhance presynaptic inhibition at all levels of the neuraxis and that this effect requires not only the presence of GABA but is also dependent on an activity of GABA-ergic neurons. Benzodiazepines also appear to enhance postsynaptic inhibition where this is mediated by GABA. Many actions of benzodiazepines can be tentatively explained by a stimulus-bound enhancement of GABA effects.     

Adaptation-induced plasticity of orientation tuning in adult visual cortex

A key emergent property of the primary visual cortex (V1) is the orientation selectivity of its neurons. The extent to which adult visual cortical neurons can exhibit changes in orientation selectivity is unknown. Here we use single-unit recording and intrinsic signal imaging in V1 of adult cats to demonstrate systematic repulsive shifts in orientation preference following short-term exposure (adaptation) to one stimulus orientation. In contrast to the common view of adaptation as a passive process by which responses around the adapting orientation are reduced, we show that changes in orientation tuning also occur due to response increases at orientations away from the adapting stimulus. Adaptation-induced orientation plasticity is thus an active time-dependent process that involves network interactions and includes both response depression and enhancement.     

二甲双胍调节初级视觉皮层兴奋性和抑制性平衡及改善视觉功能的研究

大脑皮层中兴奋和抑制系统之间的动态平衡决定了皮层神经元对刺激的反应特性.已有研究表明,二甲双胍能够诱导 γ-氨基丁酸受体向突触后膜聚集,增强神经系统的抑制效果.本课题进一步探讨了二甲双胍对初级视觉皮层兴奋和抑制系统平衡的调节作用,以及其改善小鼠视觉功能的潜力.实验使用成年雄性小鼠,实验组(metformin)10只每天...     

GABA-opioid interactions in the globus pallidus: [D-Ala2]-Met-enkephalinamide attenuates potassium-evoked GABA release after nigrostriatal lesion

The motor signs of Parkinson's disease have been partly attributed to an overinhibition of the external globus pallidus (GP) that results from hyperactivity of striatopallidal GABA/enkephalinergic neurons. The goals of this study were to measure basal levels of extracellular fluid GABA in the GP of normal cats, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated parkinsonian cats and cats spontaneously recovered from MPTP-induced parkinsonism, and to examine the effects of opioid receptor activation on potassium (K+)-evoked GABA release in the GP in these animals. Basal GP GABA levels were increased 75% from normal in parkinsonian animals 1 week after MPTP administration and returned to control levels in recovered animals 6 weeks after MPTP administration. No significant differences were observed in K+-evoked GABA release across conditions. The opioid receptor agonist [D-Ala2]-Met-Enkephalinamide (DALA) significantly attenuated K+-evoked GABA release in the GP of MPTP-treated symptomatic and recovered cats, but had no significant effect on GABA release in normal animals. These data show that basal GP GABA levels are elevated coincident with expression of parkinsonian signs and return to normal in animals that have functionally compensated for a nigrostriatal lesion. DALA-induced inhibition of pallidal GABA release after a dopamine-depleting lesion, suggests that enkephalin may attenuate GABA release in the GP specifically after striatal dopamine loss.     

Retinal and cortical nonlinearities combine to produce masking in V1 responses to plaids

The visual response of a cell in the primary visual cortex (V1) to a drifting grating stimulus at the cell’s preferred orientation decreases when a second, perpendicular, grating is superimposed. This effect is called masking. To understand the nonlinear masking effect, we model the response of Macaque V1 simple cells in layer 4Cα to input from magnocellular Lateral Geniculate Nucleus (LGN) cells. The cortical model network is a coarse-grained reduction of an integrate-and-fire network with excitation from LGN input and inhibition from other cortical neurons. The input is modeled as a sum of LGN cell responses. Each LGN cell is modeled as the convolution of a spatio-temporal filter with the visual stimulus, normalized by a retinal contrast gain control, and followed by rectification representing the LGN spike threshold. In our model, the experimentally observed masking arises at the level of LGN input to the cortex. The cortical network effectively induces a dynamic threshold that forces the test grating to have high contrast before it can overcome the masking provided by the perpendicular grating. The subcortical nonlinearities and the cortical network together account for the masking effect. Melinda Koelling is formerly from Center for Neural Science and Courant Institute, New York University.     

Dopamine D1 receptor signaling system regulates ryanodine receptor expression after intermittent exposure to methamphetamine in primary cultures of midbrain and cerebral cortical neurons

Regulatory mechanisms of ryanodine receptor (RyR) expression are not well known, although methamphetamine (METH) has been reported to up-regulate RyRs in mouse brain. This study investigate regulatory mechanisms of RyR expression by dopaminergic system using the midbrain and cerebral cortical neurons in primary culture intermittently exposed to METH and dopamine receptor (DR) agonists (1 h/day, for 3 days). Intermittent METH (10 μM) exposure enhanced RyR-1 and -2 proteins and their mRNA, but not RyR-3 expression in the both types of the neurons. These METH-induced increases of RyR proteins and their mRNA were dose-dependently blocked by SCH23390 (a selective D(1) DR antagonist), but not a D(2)DR antagonist sulpiride, suggesting a regulatory role of D(1)DRs in RyR expression by METH in these neurons. In cerebral cortical neurons, intermittent SKF82958 (a selective D(1)DR agonist) exposure increased RyR-1 and -2 proteins and their mRNA, whereas quinpirole (a selective D(2)DR agonist) showed no effects. KT5720, a protein kinase A inhibitor, dose-dependently attenuated the METH-stimulated RyR-1 and -2 expressions in cerebral cortical neurons. METH significantly increased phosphorylation of cAMP-response element-binding protein, which was completely suppressed by SCH23390. These results indicate that RyR-1 and -2 expressions are regulated by D(1)DRs via the signal transduction linked to D(1)DRs.     

Anodal transcranial direct current stimulation reduces psychophysically measured surround suppression in the human visual cortex

Transcranial direct current stimulation (tDCS) is a safe, non-invasive technique for transiently modulating the balance of excitation and inhibition within the human brain. It has been reported that anodal tDCS can reduce both GABA mediated inhibition and GABA concentration within the human motor cortex. As GABA mediated inhibition is thought to be a key modulator of plasticity within the adult brain, these findings have broad implications for the future use of tDCS. It is important, therefore, to establish whether tDCS can exert similar effects within non-motor brain areas. The aim of this study was to assess whether anodal tDCS could reduce inhibitory interactions within the human visual cortex. Psychophysical measures of surround suppression were used as an index of inhibition within V1. Overlay suppression, which is thought to originate within the lateral geniculate nucleus (LGN), was also measured as a control. Anodal stimulation of the occipital poles significantly reduced psychophysical surround suppression, but had no effect on overlay suppression. This effect was specific to anodal stimulation as cathodal stimulation had no effect on either measure. These psychophysical results provide the first evidence for tDCS-induced reductions of intracortical inhibition within the human visual cortex.     

Investigation of functional organization of receptive fields in the cat visual cortex

Receptive fields of neurons in Area 17 of the visual cortex were investigated in cats. Concentrically shaped fields, fields responding selectively to orientation of a strip or edge, and fields which can be regarded as intermediate between the first two types are described. The boundary between zones of summation and of lateral inhibition coincides in some receptive fields with the boundary between central and peripheral zones with opposite forms of response, while in other fields they do not coincide. For some cells there is no peripheral zone or it may disappear with worsening of the state of function. Cells were observed for which an increase in area of the stimulus in the central zone inhibits the response reaction. Analysis of these data suggests that several cells of the geniculate ganglion converge on some cortical neurons, and several cortical cells on others. An effect of adaptive inhibition was found in which constant illumination of an area in the center of the receptive field inhibits the response in another part. It is shown that this effect is unconnected with the action of scattered light. Constant illumination of the peripheral part of the receptive field deinhibits adaptive inhibition. The boundary between the zones of summation and of lateral inhibition coincides with the boundary between the zones of adaptive inhibition and deinhibition.I. V. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 1, No. 1, pp. 90–100, July–August, 1969.     

Ensemble activity of neurons in the visual, frontal, and sensorimotor cortices and dorsal striatum during actualization of behavioral program under conditions of strategy choice

Unit and network activity of neurons in the visual, sensorimotor, and frontal cortical areas and dorsal striatum was investigated in cats under conditions of choice of the reinforcement value depending on its delay. The animals did not differ from each other in behavior. After immediate or delayed responses cats got low- or highly-valuable reinforcement, respectively. Single-unit activity in the visual and sensorimotor cortical areas and dorsal striatum was similar during performance of immediate and delayed responses. However, significant inhibition was observed in the frontal neurons during the delay period. The network activity of visual and frontal cortex displayed smaller number of interneuronal interactions during delayed responses as compared to immediate reactions. The network activity of neurons in the brain structures under study pointed to the interstructural interaction, but only during delayed reactions, steady interneuronal communication was observed between the frontal cortex and dorsal striatum. Thus, both types of estimation of cellular activity revealed differences in the ensemble organization during different types of behavior and showed specific reactions of neuronal ensembles.