Existence Of Neurons Research Articles

Small numbers are sensed directly, high numbers constructed from size and density

Two theories compete to explain how we estimate the numerosity of visual object sets. The first suggests that the apparent numerosity is derived from an analysis of more low-level features like size and density of the set. The second theory suggests that numbers are sensed directly. Consistent with the latter claim is the existence of neurons in parietal cortex which are specialized for processing the numerosity of elements in the visual scene. However, recent evidence suggests that only low numbers can be sensed directly whereas the perception of high numbers is supported by the analysis of low-level features. Processing of low and high numbers, being located at different levels of the neural hierarchy should involve different receptive field sizes. Here, I tested this idea with visual adaptation. I measured the spatial spread of number adaptation for low and high numerosities. A focused adaptation spread of high numerosities suggested the involvement of early neural levels where receptive fields are comparably small and the broad spread for low numerosities was consistent with processing of number neurons which have larger receptive fields. These results provide evidence for the claim that different mechanism exist generating the perception of visual numerosity. Whereas low numbers are sensed directly as a primary visual attribute, the estimation of high numbers however likely depends on the area size over which the objects are spread.

IMAGING OF AGEING AND SEEDING EFFECTS ON TAU PATHOLOGY IN THE MOUSE TAUOPATHY MODEL

The formation of neurofibrillary tangles (NFTs) consisting of hyperphosphorylated tau protein is one of the pathological hallmarks of Alzheimer's disease (AD). Recent studies using tau transgenic mouse models have revealed that tau protein can spread from cell to cell in a prion-like manner, leading to disease progression in a stereotypical and time-dependent fashion. However, much is still unknown about whether these transgenic mice constitute valid models of human AD and the factors that regulate the pathological hyperphosphorylation of tau. We used a transgenic mouse model expressing the 383 amino acid isoform of human tau with the P301S mutation. To analyse the expression pattern of mutated human tau and hyperphosphorylated tau, we used immunohistochemistry and confocal microscopy on 3-month-old and 7-month-old mice that were either non-seeded or seeded by injection of synthetic fibrillar tau. In non-seeded 3-month-old mice, only 74.80 ± 0.99% of frontal cortex layer 2/3 neurons express the tau transgene, with different neurons showing varying levels of expression. Remarkably, even in 3-month-old mice, 55.39 ± 1.00% of frontal cortex neurons already contain low diffuse levels of hyperphosphorylated tau. We showed that this group of vulnerable neurons could be induced to develop pathologically high levels of tau suggestive of NFTs with both age and seeding, with the proportion of neurons containing pathological levels of tau increasing from 0.02% at 3 months to 9.54% (non-seeded) and 12.97% (seeded) at 7 months of age. The existence of neurons not expressing the transgene should be taken into account when using the P301S model to investigate other factors modulating tau hyperphosphorylation and spreading. Contrary to previous findings, most human tau-expressing neurons in young mice already contain low levels of hyperphosphorylated tau, which predisposes them to NFT pathology with age or seeding. Expression pattern of human tau in the frontal cortex of the P301S transgenic mouse model. Age and seeding are independently associated with increased levels of pathological tau protein.

Long-Range, Pattern-Dependent Contextual Effects in Early Human Visual Cortex

The standard view of neurons in early visual cortex is that they behave like localized feature detectors. Here we demonstrate that processing in early visual areas goes beyond feature detection by showing that neural responses are greater when a feature deviates from its context compared to when it does not deviate from its context. Using psychophysics, fMRI, and electroencephalography methodologies, we measured neural responses to an oriented Gabor ("target") embedded in various visual patterns as defined by the relative orientation of flanking stimuli. We first show using psychophysical contrast adaptation and fMRI that a target that differs from its context results in more neural activity compared to a target that is contained within an alternating sequence, suggesting that neurons in early visual cortex are sensitive to large-scale orientation patterns. Next, we use event-related potentials to show that orientation deviations affect the earliest sensory components of the target response. Finally, we use forced-choice classification of "noise" stimuli to show that we are more likely to "see" orientations that deviate from the context. Our results suggest that early visual cortex is sensitive to global patterns in images in a way that is markedly different from the predictions of standard models of cortical visual processing.

Blood pressure regulation by C1 neurons in the rostral ventrolateral medulla: new light on the subject

Blood pressure regulation by C1 neurons in the rostral ventrolateral medulla: new light on the subject

Intrinsic Bursters Increase the Robustness of Rhythm Generation in an Excitatory Network

The pre-Botzinger complex (pBC) is a vital subcircuit of the respiratory central pattern generator. Although the existence of neurons with pacemaker-like bursting properties in this network is not questioned, their role in network rhythmogenesis is unresolved. Modeling is ideally suited to address this debate because of the ease with which biophysical parameters of individual cells and network architecture can be manipulated. We modeled the parameter variability of experimental data from pBC bursting pacemaker and nonpacemaker neurons using a modified version of our previously developed pBC neuron and network models. To investigate the role of pacemakers in networkwide rhythmogenesis, we simulated networks of these neurons and varied the fraction of the population made up of pacemakers. For each number of pacemaker neurons, we varied the amount of tonic drive to the network and measured the frequency of synchronous networkwide bursting produced. Both excitatory networks with all-to-all coupling and sparsely connected networks were explored for several levels of synaptic coupling strength. Networks containing only nonpacemakers were able to produce networkwide bursting, but with a low probability of bursting and low input and output ranges. Our results indicate that inclusion of pacemakers in an excitatory network increases robustness of the network by more than tripling the input and output ranges compared with networks containing no pacemakers. The largest increase in dynamic range occurs when the number of pacemakers in the network is greater than 20% of the population. Experimental tests of our model predictions are proposed.

Spatiotopic Transfer of Visual-Form Adaptation across Saccadic Eye Movements

Although conscious perception is smooth and continuous, the input to the visual system is a series of short, discrete fixations interleaved with rapid shifts of the eye. One possible explanation for visual stability is that internal maps of objects and their visual properties are remapped around the time of saccades, but numerous studies have demonstrated that visual patterns are not combined across saccades. Here, we report that visual-form aftereffects transfer across separate fixations when adaptor and test are presented in the same spatial position. The magnitude of the transsaccadic adaptation increased with stimulus complexity, suggesting a progressive construction of spatiotopic receptive fields along the visual-form pathway. These results demonstrate that basic shape information is combined across saccades, allowing for predictive and consistent information from the past to be incorporated into each new fixation.

Contrast Adaptation and Representation in Human Early Visual Cortex

The human visual system can distinguish variations in image contrast over a much larger range than measurements of the static relationship between contrast and response in visual cortex would suggest. This discrepancy may be explained if adaptation serves to re-center contrast response functions around the ambient contrast, yet experiments on humans have yet to report such an effect. By using event-related fMRI and a data-driven analysis approach, we found that contrast response functions in V1, V2, and V3 shift to approximately center on the adapting contrast. Furthermore, we discovered that, unlike earlier areas, human V4 (hV4) responds positively to contrast changes, whether increments or decrements, suggesting that hV4 does not faithfully represent contrast, but instead responds to salient changes. These findings suggest that the visual system discounts slow uninformative changes in contrast with adaptation, yet remains exquisitely sensitive to changes that may signal important events in the environment.

Spontaneously active cells induce state transitions in a model of olfactory cortex

The existence of neurons with intrinsic oscillations does not in itself explain the synchronization of local populations of neurons, but it is likely to pace population rhythms when the neurons are suitably coupled by chemical and/or electrical synapses. In the present study, we have investigated the role of spontaneously active cells as noisy or pacemaker units in setting global oscillations in a three-layered cortical model. The presence of a small number of noisy (spontaneously active) units induce oscillations at the network level in the range of the gamma rhythm. The number of noisy units in the network and their type (excitatory or inhibitory or excitatory and inhibitory together) determines the emergence of regular oscillations or aperiodic (chaotic) behaviour. It also determines the onset of the global behaviour. On replacing a noisy unit by a pacemaker unit, similar gamma oscillations were generated. With both noisy and pacemaker units, we found that certain characteristics of the spontaneous activity determine the delay period for the onset of global activity. Preliminary studies have been carried out with spontaneously active units having a chaotic dynamics but the results are much similar to that with a noisy burst. Different functional roles have been suggested for cortical oscillations, such as determining global functional states and specifying connectivity during development. Oscillations at different frequency bands, in particular in the gamma band (around 40 Hz), have also been associated with memory and attention. The presence of spontaneously active neurons, either with noisy or oscillatory activity, could be responsible for global oscillations in the absence of external stimuli in certain cortical areas in the mature brain.

Motion energy versus position tracking: spatial, temporal and chromatic parameters

The fundamental question in motion perception is whether motion is an interpretation imposed on an object or feature perceived at separate positions at sequential instants, or whether it is the response of direction-sensitive detectors that can extract the motion-energy in the stimulus, i.e. the orientation of spatio-temporal energy. To answer this question we constructed stimuli whose position cahnges in one direction while the motion energy contained in the same spatial frequency moved in the same or the opposite direction (by superimposing moving sinusoidal gratings on stationary gratings of the same spatial frequency and orientation). In every case tested (0.25-25 Hz temporal frequency; 0.25–1.0 cyc/deg spatial frequency; achromatic and equiluminant contrast), the perceived direction of motion was in the direction of motion energy, indicating the existence of neurons which compute motion direction without explicitly computing spatial position. The measurements also confirmed that motion-energy computations can be modeled as separable in spatial and temporal frequency.

The history of radial glia

Radial glial cells are now recognized as a transient population that serves as scaffolding for neuronal migration. The recognition of the existence and role of radial glia has not been smooth, and here we provide a brief historical overview on the pioneering studies on this subject. The histologists and embryologists Albert Kölliker and Wilhelm His performed seminal investigations on cortical morphogenesis in the last decades of the 19th century. However, the introduction of the silver impregnation Golgi technique, and its diffusion in the late 1880s, played a crucial role in the detection of radial glial processes. The radial arrangement of fibers emerging from the neuroepithelium lining the central canal was initially detected in the embryonic spinal cord by Camillo Golgi himself. The first Golgi impregnation of the cerebral cortex of mammalian fetuses was performed by Giuseppe Magini, who detected radial fibers extending from the ventricular neuroepithelium, and observed cells intercalated along these processes. Radial fibers, regarded as epithelial or ependymal processes, were then observed in the developing spinal cord and cerebral cortex by several investigators. Santiago Ramón y Cajal was the first to suggest that radial fibers were modified astrocytic processes functioning as a support during cortical histogenesis. Cajal acknowledged Magini’s findings, but he criticized Magini’s observations on the existence of neurons along radial fibers. With the advent of electron microscopy, the existence of radially arranged glial processes along which young neurons migrate was finally ascertained in the early 1970s by Pasko Rakic, thus opening a new era in the cellular and molecular biology of radial glia.

Cellular localization and laminar distribution of NMDAR1 mRNA in the rat cerebral cortex.

N-methyl-D-aspartate (NMDA) receptors, which play a critical role in many cortical functions, are composed of a heteromeric assembly of different subunits: of these, the NMDA receptor subunit 1 (NMDAR1) is a constant component of, and thus an excellent marker for, NMDA receptors. In this study, we have investigated the cellular localization and laminar distribution of NMDAR1 mRNA in the cerebral cortex of adult rats by in situ hybridization histochemistry with a 35S-labeled cRNA probe. Specificity and background levels were determined in adjacent sections incubated with a 35S-labeled sense RNA. In sections incubated with the antisense RNA probe, specific hybridization signal was observed in a large number of cells. Some cells, however, did not appear to contain NMDAR1 mRNA. The vast majority of these unlabeled cells were small, suggesting that they are astrocytes or other small nonneuronal cells. Double-labeling studies with in situ hybridization histochemistry and immunocytochemistry with antibodies to glial fibrillary acidic protein (GFAP) showed that about 95.7% of the GFAP-positive cells did not express NMDAR1 mRNA, indicating that virtually all astrocytes do not contain this transcript. A semiquantitative evaluation of cortical neurons, defined as those cells larger than the GFAP-positive astrocytes, revealed that about 80% were associated with silver grains. The number of silver grains associated with every neuron was determined from sections exposed for 15 days, the background level was subtracted, and all labeled neurons were grouped into five groups: A (< or = 10 grains), B (11-20 grains), C (21-30 grains), D (31-40 grains), and E (> 40 grains). The number of neurons belonging to each group was then evaluated according to their occurrence in each cortical layer. In layer I all labeled neurons were in group A, whereas in layers II-III and V-VI positive neurons were in group A-E. In layer IV most neurons were in groups A and B, whereas only a few were in group E. These observations indicate that 1) virtually all cortical cells containing NMDAR1 mRNA in adult rats are neurons; 2) about 80% of all cortical neurons express NMDAR1 mRNA; and 3) labeled neurons can be divided into several groups on the basis of NMDAR1 mRNA levels expressed, which presumably reflect the number of NMDA receptors. The existence of neurons with a different number of receptors may be a critical factor for determining the physiological effect of NMDA receptor activation.(ABSTRACT TRUNCATED AT 400 WORDS)

Histo- and immunocytochemical characterization of the neurons of the mucosal plexus in the rat colon.

The mucosal plexus of the rat colon descendens is constituted of a network of nerves that, in contrast to most other segments of the digestive tract, contains also ganglia. The ganglia, consisting of neurons and glial cells, are located in the basal part of the lamina propria at distances between 100 and 1,200 microns. They are not vascularized. The neurons in these ganglia were characterized by means of: (1) the histochemical demonstration of acetylcholinesterase (AChE) activity, (2) the immunocytochemical identification of neurofilament proteins (NFP; 200 kD) and (3) their ultrastructure. The glial cells, which were AChE negative, could be distinguished from the neurons by differences in size and chromatin pattern. All neurons of the mucosal plexus reveal AChE activity in the perikaryon, but only parts of the axons are AChE positive. NFP-like immunoreactivity was detected in the perikarya but only in a minor part of the axons. These findings confirm previous light-microscopical observations and add new evidence for the existence of neurons (ganglia) in the mucosal plexus of the rat colon.

Spinal neurons with branched axons traveling in both the dorsal and dorsolateral funiculi

Antidromic search stimuli were delivered to cervical (C2–C3) dorsal and dorsolateral funiculi that were dissected apart from one another and from the rest of the spinal cord. Fifty-six neurons were antidromically identified in the dorsal horn of the lumbosacral enlargement. Of these neurons, 23 were activated antidromically from both the dorsal columns and the ipsilateral dorsolateral funiculus. The neurons were found at depths corresponding to laminae III and IV. About half of the neurons responded only to innocuous, tactile stimuli whereas the other half responded to both innocuous and noxious stimuli. The existence of neurons with branched axons ascending both the dorsal and dorsolateral funiculi raises the possibility that the dorsal column postsynaptic and spinocervical tracts may not be completely independent projections.

Immunocytochemical evidence for the existence of GABAergic neurons in the nucleus raphe dorsalis. possible existence of neurons containing serotonin and GABA

It has been established that nerve cell bodies of the nucleus raphe dorsalis (NRD) belong to ascending 5-hydroxytryptamine systems. These neurons could be modulated by GABAergic interneurons or interposed GABA neurons. A high glutamate decar☐ylase (GAD) activity in the NRD and a specific high-affinity uptake mechanism for GABA suggest the presence of GABA synthesizing elements in the NRD. Anti-GAD antibodies were used by an immunocytochemical procedure to demonstrate the presence of GABAergic elements. Anti-GAD antibodies were previously tested in the cerebellum and substantia nigra. Large amounts of GAD-positive reaction product were observed in the cytoplasm of some neurons (fusiform, ovoid or multipolar) or appeared as punctate deposits apposed to dendrites, soma and dispersed in the neuropil of the NRD. At the electron microscopic level, GAD-positive reaction product was observed within the cytoplasm of numerous somata in sections from colchicine-treated rats. GAD-positive staining was observed in numerous fibers or axonal terminals and two types of morphologically different fibers could be distinguished. The first displays small clear vesicles and few large granular vesicles (LGV) (80–100 nm), the second displays only clear round vesicles (40–60 nm). After 5,7-dihydroxytryptamine treatment (a neurotoxic for 5-HT terminals), the immunocytochemical labeling is much decreased. Some reactive neurons are still dispersed in the nucleus but the fibers containing LGV are no longer observed. These results strongly suggest that some neuronal elements in the NRD are morphologically, pharmacologically and anatomically similar to 5-HT neurons described at this level. Such cell elements could possess a double GABA and 5-HT potentiality. If this is not the case, a population of GABA neurons could be sensitive to 5,7-DHT and so have the capacity to take up 5-HT. The other reactive elements, insensitive to 5,7-DHT, could represent the GABAergic interneurons postulated at this level. Numerous GAD positive fibers or axon terminals were observed in synaptic contact with dendrites, axons or soma of other neurons. The chemical nature of the neuronal postsynaptic elements remains unknown. These findings strongly support the hypothesis for GABA-mediated inhibition in the NRD.

On the existence of neurones in the human visual system selectively sensitive to the orientation and size of retinal images.

1. It was found that an occipital evoked potential can be elicited in the human by moving a grating pattern without changing the mean light flux entering the eye. Prolonged viewing of a high contrast grating reduces the amplitude of the potential evoked by a low contrast grating.2. This adaptation to a grating was studied psychophysically by determining the contrast threshold before and after adaptation. There is a temporary fivefold rise in contrast threshold after exposure to a high contrast grating of the same orientation and spatial frequency.3. By determining the rise of threshold over a range of spatial frequency for a number of adapting frequencies it was found that the threshold elevation is limited to a spectrum of frequencies with a bandwidth of just over an octave at half amplitude, centred on the adapting frequency.4. The amplitude of the effect and its bandwidth are very similar for adapting spatial frequencies between 3 c/deg. and 14 c/deg. At higher frequencies the bandwidth is slightly narrower. For lower adapting frequencies the peak of the effect stays at 3 c/deg.5. These and other findings suggest that the human visual system may possess neurones selectively sensitive to spatial frequency and size. The orientational selectivity and the interocular transfer of the adaptation effect implicate the visual cortex as the site of these neurones.6. This neural system may play an essential preliminary role in the recognition of complex images and generalization for magnification.