Neurons In Cortical Areas Research Articles

Effects of armodafinil nanocrystal nasal hydrogel on recovery of cognitive function in sleep-deprived rats

Armodafinil is typically used in clinical practice to maintain cognition and wakefulness in patients suffering from sleep deprivation. However, its poor water solubility and large dosage limit its effective application. Herein, we formulated armodafinil in a nanocrystal hydrogel (NCsG) with appropriate fluidity and viscosity, capable of rapidly dissolving after staying in the nasal cavity for > 4 h and then penetrating the mucosa as quickly as possible in vitro. We found that armodafinil NCsG was biologically safe, as it had no visible ciliary toxicity, as well as extremely stable due to the existence of intermolecular hydrogen-bonding forces. Nasal administration of armodafinil NCsG proved to be more efficient and targeted than oral administration due to its preferential absorption in plasma and more-concentrated distribution in the brain. In addition, compared with the model group, sleep-deprived rats treated with NCsG undergoing Morris water maze (MWM) behavioral experiments had shorter escape latency and much more shuttle times across the platform. Meanwhile, in the open-field test (OFT), these same rats had longer periods of movement in the center, longer time spent upright, and lower anxiety, which clearly demonstrated improved cognitive awareness and wakefulness after intranasal administration. Moreover, we speculated that armodafinil NCsG had a protective effect on hippocampal neurons in Cortical Area 1 (CA1), which is closely related to cognitive function, by upregulating brain-derived neurotrophic factor (BDNF) protein expression. Consequently, the intranasal administration of armodafinil NCsG could serve as a promising integrated-control measure for sleep deprivation.

Digital Implementation of the Two-Compartmental Pinsky-Rinzel Pyramidal Neuron Model.

It is believed that brain-like computing system can be achieved by the fusion of electronics and neuroscience. In this way, the optimized digital hardware implementation of neurons, primary units of nervous system, play a vital role in neuromorphic applications. Moreover, one of the main features of pyramidal neurons in cortical areas is bursting activities that has a critical role in synaptic plasticity. The Pinsky-Rinzel model is a nonlinear two-compartmental model for CA3 pyramidal cell that is widely used in neuroscience. In this paper, a modified Pinsky-Rinzel pyramidal model is proposed by replacing its complex nonlinear equations with piecewise linear approximation. Next, a digital circuit is designed for the simplified model to be able to implement on a low-cost digital hardware, such as field-programmable gate array (FPGA). Both original and proposed models are simulated in MATLAB and next digital circuit simulated in Vivado is compared to show that obtained results are in good agreement. Finally, the results of physical implementation on FPGA are also illustrated. The presented circuit advances preceding designs with regards to the ability to replicate essential characteristics of different firing responses including bursting and spiking in the compartmental model. This new circuit has various applications in neuromorphic engineering, such as developing new neuroinspired chips.

A neural basis for the spatial suppression of visual motion perception.

In theory, sensory perception should be more accurate when more neurons contribute to the representation of a stimulus. However, psychophysical experiments that use larger stimuli to activate larger pools of neurons sometimes report impoverished perceptual performance. To determine the neural mechanisms underlying these paradoxical findings, we trained monkeys to discriminate the direction of motion of visual stimuli that varied in size across trials, while simultaneously recording from populations of motion-sensitive neurons in cortical area MT. We used the resulting data to constrain a computational model that explained the behavioral data as an interaction of three main mechanisms: noise correlations, which prevented stimulus information from growing with stimulus size; neural surround suppression, which decreased sensitivity for large stimuli; and a read-out strategy that emphasized neurons with receptive fields near the stimulus center. These results suggest that paradoxical percepts reflect tradeoffs between sensitivity and noise in neuronal populations.

The Disconnection Hypothesis inAlzheimer's Disease Studied Through Multimodal Magnetic Resonance Imaging: Structural, Perfusion, and Diffusion Tensor Imaging.

According to the so-called disconnection hypothesis, the loss of synaptic inputs from the medial temporal lobes (MTL) in Alzheimer's disease (AD) may lead to reduced activity of target neurons in cortical areas and, consequently, to decreased cerebral blood flow (CBF) in those areas. The aim of this study was to assess whether hypoperfusion in parietotemporal and frontal cortices of patients with mild cognitive impairment who converted to AD (MCI-c) and patients with mild AD is associated with atrophy in the MTL and/or microstructural changes in the white matter (WM) tracts connecting these areas. We assessed these relationships by investigating correlations between CBF in hypoperfused areas, mean cortical thickness in atrophied regions of the MTL, and fractional anisotropy (FA) in WM tracts. In the MCI-c group, a strong correlation was observed between CBF of the superior parietal gyri and FA in the parahippocampal tracts (left: r = 0.90, p < 0.0001; right: r = 0.597, p = 0.024), and between FA in the right parahippocampal tract and the right precuneus (r = 0.551, p = 0.041). No significant correlations between CBF in hypoperfused regions and FA in the WM tract were observed in the AD group. These results suggest an association between perfusion deficits and altered WM tracts in prodromal AD, while microvasculature impairments may have a greater influence in more advanced stages. We did not find correlations between cortical thinning in the medial temporal lobes and decreased FA in the WM tracts of the limbic system in either group.

Plasticity of spatial hearing: behavioural effects of cortical inactivation

The contribution of auditory cortex to spatial information processing was explored behaviourally in adult ferrets by reversibly deactivating different cortical areas by subdural placement of a polymer that released the GABAA agonist muscimol over a period of weeks. The spatial extent and time course of cortical inactivation were determined electrophysiologically. Muscimol-Elvax was placed bilaterally over the anterior (AEG), middle (MEG) or posterior ectosylvian gyrus (PEG), so that different regions of the auditory cortex could be deactivated in different cases. Sound localization accuracy in the horizontal plane was assessed by measuring both the initial head orienting and approach-to-target responses made by the animals. Head orienting behaviour was unaffected by silencing any region of the auditory cortex, whereas the accuracy of approach-to-target responses to brief sounds (40 ms noise bursts) was reduced by muscimol-Elvax but not by drug-free implants. Modest but significant localization impairments were observed after deactivating the MEG, AEG or PEG, although the largest deficits were produced in animals in which the MEG, where the primary auditory fields are located, was silenced. We also examined experience-induced spatial plasticity by reversibly plugging one ear. In control animals, localization accuracy for both approach-to-target and head orienting responses was initially impaired by monaural occlusion, but recovered with training over the next few days. Deactivating any part of the auditory cortex resulted in less complete recovery than in controls, with the largest deficits observed after silencing the higher-level cortical areas in the AEG and PEG. Although suggesting that each region of auditory cortex contributes to spatial learning, differences in the localization deficits and degree of adaptation between groups imply a regional specialization in the processing of spatial information across the auditory cortex.

The Influence of Contrasts on Directional and Spatial Frequency Tuning in Visual Cortex Areas 17/18 of the Cat

PurposeThe purpose of this study was to investigate the effects of contrast display exposure on neuronal directional and spatial frequency tuning. Neuronal responses were recorded from ninety-four neurons in cortical areas 17 and 18 in two adult cats.MethodsA multi-channel microelectrode was implanted in cortical areas 17 and 18 of two paralyzed and anaesthetized cats. Various drifting sinusoidal grating contrast displays were presented to one of the cats' eyes in the visual field. Contour plots based on the neuronal responses to the drifting sinusoidal grating displays using various contrasts (i.e., 0.4, 0.7, and 1.0) and velocities (i.e., 4.6, 13.9, 23.1, 32.3, 41.5, 50.8, and 60.0 deg/sec) were plotted as a function of the spatial frequency and the direction associated with each velocity and contrast used.ResultsFive parameters were extracted from these contour plots: 1) optimum response, 2) preferred direction, 3) optimum spatial frequency, 4) directional tuning width, and 5) spatial frequency bandwidth. To determine the optimal velocity, each parameter was plotted against each of the specific display contrasts used, and a 'best fit' line was established. Response amplitudes were dependent on the type of contrast utilized; however, the spatial frequency and directional tuning properties were stable for the cortical neurons assessed.ConclusionsThe results of the presentation of different contrasts on neuronal directional and spatial frequency tuning are consistent with behavioral results when medium and high contrast displays are used.

Information geometry in neural spike sequences

An information geometrical method is developed for characterizing or classifying neurons in cortical areas whose spike rates fluctuate in time. The interspike intervals (ISIs) of a spike sequence of a neuron is modeled as a gamma process with a time-variant spike rate, a fixed shape parameter and a fixed absolute refractory period. We formulate the problem of estimating the fixed parameters as semiparametric estimation and apply an information geometrical method to derive the optimal estimators from a statistical viewpoint.

Visual response properties of neurons in cortical areas MT and MST projecting to the dorsolateral pontine nucleus or the nucleus of the optic tract in macaque monkeys

Neurons in cortical medial temporal area (MT) and medial superior temporal area (MST) projecting to the dorsolateral pontine nucleus (DLPN) and/or to the nucleus of the optic tract and dorsal terminal nucleus (NOT-DTN) were identified by antidromic electrical stimulation in five macaque monkeys. Neurons projecting to either target were located in close proximity to each other, and in all subregions of MT and MST sampled. Only a small percentage of the antidromically identified projection neurons (4.4%) sent branches to both the NOT-DTN and the DLPN. Antidromic latencies of neurons projecting to the NOT-DTN (0.9-6 ms, median 2.1 ms) and to the DLPN (0.8-5 ms, median 2.0 ms) did not differ significantly. Visual response properties of the neurons antidromically activated from either site did not differ significantly from those of cells that were not so activated. On the population level only neurons activated from the NOT-DTN had a clear preference for ipsiversive stimulus movement, whereas the neurons activated from the DLPN and neurons not antidromically activated from either target had no common directional preference. These results are discussed in terms of specification of cortico-subcortical connections and with regard to pathways underlying slow eye movements in different visuomotor behaviours.

The Neural Basis for Combinatorial Coding in a Cortical Population Response

We have used a combination of theory and experiment to assess how information is represented in a realistic cortical population response, examining how motion direction and timing is encoded in groups of neurons in cortical area MT. Combining data from several single-unit experiments, we constructed model population responses in small time windows and represented the response in each window as a binary vector of 1s or 0s signifying spikes or no spikes from each cell. We found that patterns of spikes and silence across a population of nominally redundant neurons can carry up to twice as much information about visual motion than does population spike count, even when the neurons respond independently to their sensory inputs. This extra information arises by virtue of the broad diversity of firing rate dynamics found in even very similarly tuned groups of MT neurons. Additionally, specific patterns of spiking and silence can carry more information than the sum of their parts (synergy), opening up the possibility for combinatorial coding in cortex. These results also held for populations in which we imposed levels of nonindependence (correlation) comparable to those found in cortical recordings. Our findings suggest that combinatorial codes are advantageous for representing stimulus information on short time scales, even when neurons have no complicated, stimulus-dependent correlation structure.

Differential effects of stress and amphetamine administration on Fos‐like protein expression in corticotropin releasing factor‐neurons of the rat brain

Corticotropin releasing factor (CRF) appears to be critical for the control of important aspects of the behavioral and physiological response to stressors and drugs of abuse. However, the extent to which the different brain CRF neuronal populations are similarly activated after stress and drug administration is not known. We then studied, using double immunohistochemistry for CRF and Fos protein, stress and amphetamine-induced activation of CRF neurons in cortex, central amygdala (CeA), medial parvocellular dorsal, and submagnocellular parvocellular regions of the paraventricular nucleus of the hypothalamus (PVNmpd and PVNsm, respectively) and Barrington nucleus (Bar). Neither exposure to a novel environment (hole-board, HB) nor immobilization (IMO) increased Fos-like immunoreactivity (FLI) in the CeA, but they did to the same extent in cortical regions. In other regions only IMO increased FLI. HB and IMO both failed to activate CRF+ neurons in cortical areas, but after IMO, some neurons expressing FLI in the PVNsm and most of them in the PVNmpd and Bar were CRF+. Amphetamine administration increased FLI in cortical areas and CeA (with some CRF+ neurons expressing FLI), whereas the number of CRF+ neurons increased only in the PVNsm, in contrast to the effects of IMO. The present results indicate that stress and amphetamine elicited a distinct pattern of brain Fos-like protein expression and differentially activated some of the brain CRF neuronal populations, despite similar levels of overall FLI in the case of IMO and amphetamine.

Parietal Area 5 and the Initiation of Self-Timed Movements versus Simple Reactions

The timing of action has been studied extensively in reaction-time tasks in which an abrupt sensory stimulus triggers a movement. In these experiments, neurophysiologists have attempted to explain variability in movement time with variability in neuronal activity. However, in natural settings, movements are not usually triggered by abrupt sensory cues. What underlies the timing of action under such circumstances, when movements are uncoupled or only weakly coupled to abrupt events in the external world? We trained monkeys to perform the same arm movement either in direct reaction to a salient visual event, or as a self-timed action, less coupled to any obvious external trigger. Neurons in cortical area 5 exhibited phasic discharge modulations that were generally comparable for both modes of action, with some neurons increasing and others decreasing their firing rates with movement. For self-timed movements, however, there was an additional, slow ramp-up or ramp-down of activity in the few hundred milliseconds before the phasic discharge. These ramping modulations occurred well before any detectable changes in arm-muscle activity and their time course bore a striking resemblance to activity in the putamen preceding self-timed movements, observed previously. Together, the results suggest a possible mechanism for the internal timing of action within the motor system. In this model, reverberant activity in corticobasal-ganglia circuits reaches a threshold level resulting in much larger perimovement discharges within the same network, consequently driving the initiation of action.

Information Geometry of Interspike Intervals in Spiking Neurons

An information geometrical method is developed for characterizing or classifying neurons in cortical areas, whose spike rates fluctuate in time. Under the assumption that the interspike intervals of a spike sequence of a neuron obey a gamma process with a time-variant spike rate and a fixed shape parameter, we formulate the problem of characterization as a semiparametric statistical estimation, where the spike rate is a nuisance parameter. We derive optimal criteria from the information geometrical viewpoint when certain assumptions are added to the formulation, and we show that some existing measures, such as the coefficient of variation and the local variation, are expressed as estimators of certain functions under the same assumptions.

Precision pooling predicts primate perceptual performance

Moving stimuli evoke a response from a large number of neurons in cortical area MT. A new study investigates how perceptual decisions may arise from that population response, with important implications for theories of neural coding.

Relationship of Correlated Spontaneous Activity to Functional Ocular Dominance Columns in the Developing Visual Cortex

Utilizing a multielectrode array to record spontaneous and visually evoked activity of cortical neurons in area 17, we investigate the relationship between long-range correlated spontaneous activity and functional ocular dominance columns during early ferret postnatal development (P24–P29). In regions of visual cortex containing alternating ocular dominance patches, periodic fluctuations in correlated activity are observed in which spontaneous activity is most highly correlated between cortical patches exhibiting the same eye preference. However, these fluctuations are present even within large contralateral eye-dominated bands which lack any periodic alternations in ocular dominance. Thus, the organization of ocular dominance columns cannot fully account for the patterns of correlated activity we observe. Our results suggest that patterns of long-range correlated activity reflect an intrinsic periodicity of cortical connectivity that is constrained by segregated eye-specific LGN afferents.

Neuronal activity and its links with the perception of multi-stable figures.

In order to isolate the neuronal activity that relates to the making of perceptual decisions, we have made use of a perceptually ambiguous motion stimulus. This stimulus lies on the boundary between two perceptual categories that correspond to clockwise and counter-clockwise rotation of a three-dimensional figure. It consists of a two-dimensional pattern of moving dots that are capable of generating these two, distinct, three-dimensional percepts. We have studied the responses of neurons in cortical area V5/MT whilst macaque monkeys report judgements about the perceptual configuration of this stimulus. We extract a quantitative statistic called 'choice probability' that expresses the covariation of neuronal activity and perceptual choice. An analysis of choice probabilities shows that the pool of neurons involved in the perceptual decisions is a tightly constrained subset of the population of sensory neurons relevant to the perceptual task.

Motion information is spatially localized in a visual working-memory task.

We asked if the information about stimulus motion used in a visual working-memory task is localized in space. Monkeys compared the directions of two moving random-dot stimuli, sample and test, separated by a temporal delay and reported whether the stimuli moved in the same or in different directions. By presenting the two comparison stimuli in separate locations in the visual field, we determined whether information about stimulus direction was spatially localized during the storage and retrieval/comparison components of the task. Two psychophysical measures of direction discrimination provided nearly identical estimates of the critical spatial separation between sample and test stimuli that lead to a loss in threshold. Direction range thresholds measured with dot stimuli consisting of a range of local directional vectors were affected by spatial separation when a random-motion mask was introduced during the delay into the location of the upcoming test. The selective masking at the test location suggests that the information about the remembered direction was localized and available at that location. Direction difference thresholds, measured with coherently moving random dots, were also affected by separation between the two comparison stimuli. The separation at which performance was affected in both tasks increased with retinal eccentricity in parallel with the increase in receptive-field size in neurons in cortical area MT. The loss with transfer of visual information between different spatial locations suggests a contribution of cortical areas with localized receptive fields to the performance of the memory task. The similarity in the spatial scale of the storage mechanism derived psychophysically and the receptive field size of neurons in area MT suggest that MT neurons are central to this task.

The responses to illusory contours of neurons in cortex areas 17 and 18 of the cats

Responses to illusory contours (ICs) were sampled from neurons in cortical areas 17 and 18 of the anesthetized cats. For ICs sensitive cells, the differences of receptive field properties were compared when ICs and real contour stimuli were applied. Two hundred orientation or direction selective cells were studied. We find that about 42 percent of these cells were the ICs sensitive cells. Although their orientation or direction tuning curves to ICs bar and real bars were similar, the response modes (especially latency and time course) were different. The cells' responses to ICs were independent of the spatial phases of sinusoidal gratings, which composed the ICs. The cells' optimal spatial frequency to composing gratings the ICs was much higher than the one to moving gratings. Therefore, these cells really responded to the ICs rather than the line ends of composing gratings. For some kinds of velocity-tuning cells, the optimal velocity to moving ICs bar was much lower than the optimal velocity to moving bars. The present results demonstrate that some cells in areas 17 and 18 of cats have the ability to respond to ICs and have different response properties of the receptive fields to ICs and luminance boundaries via different neural mechanisms.

Expression of β-secretase mRNA in transgenic Tg2576 mouse brain with Alzheimer plaque pathology

On the basis of the recent cloning of the β-secretase, the beta-site amyloid precursor protein (APP)-cleaving enzyme (BACE), (Science, 286 (1999) 735), digoxigenin-labelled riboprobes were generated to localize the cellular expression pattern of BACE mRNA in brain sections of transgenic Tg2576 mice, overexpressing the Swedish mutation of the APP695 isoform. Non-radioactive in situ hybridization in combination with immunohistochemistry to identify the cell types and β-amyloid deposits revealed strong BACE mRNA hybridization signals in neurons of the cerebral cortex, hippocampal formation, thalamus and cholinergic basal forebrain nuclei, while astrocytes did not display any labeling. Neurons surrounding β-amyloid deposits did not demonstrate altered expression level of BACE mRNA as compared to neurons in cortical areas that are free of β-amyloid deposits, and the regional expression pattern of BACE mRNA did not correlate with the distribution of β-amyloid deposits. These data suggest that high level of expression of BACE mRNA is not necessarily related to enhanced deposition of β-amyloid plaques. To elucidate those factors that contribute to β-amyloid plaque deposition in a particular region, the transgenic Tg2576 mouse may represent an appropriate tool.

Cortical influences on the vestibular nuclei of the cat.

Our goal was to study potential substrates for cortical modulation of vestibular reflexes in the cat. In initial experiments, injections of wheat-germ-agglutinate-horseradish-peroxidase into Deiters' nucleus and the rostral descending nucleus revealed bilateral colonies of retrogradely filled neurons in cortical areas 6, 2, and 3a (about 60 cells per colony). In cats anesthetized with chloralose-urethane, we stimulated areas 2 and 3a with trains of pulses while recording from ipsilateral vestibular-nucleus neurons, which were characterized by their responses to sinusoidal tilts and tested for the presence of antidromic responses to stimulation of the upper cervical cord. A majority of the neurons was affected by cortical stimulation, showing either facilitation, inhibition, or a mixture of the two. Stimulation in area 2 was more effective than stimulation in area 3a. Despite the anatomic presence of direct cortico-vestibular projections, properties of facilitation and inhibition suggest that both were evoked by polysynaptic pathways. Cortical effects were broadly distributed to vestibular neurons without regard to responses of these neurons to sinusoidal tilts. There was no significant difference between effects on lateral and medial vestibulospinal tract neurons, but, as a group, vestibulospinal neurons were much more likely to be affected by cortical stimulation than neurons not antidromically activated from the C2 segment. We conclude that, by their influence on vestibulospinal neurons, neurons in cortical areas 2 and 3a should be able to modulate, in behaving animals, vestibular reflexes acting on the neck and limbs.

Computational Models of Thalamocortical Augmenting Responses

Repetitive stimulation of the dorsal thalamus at 7-14 Hz produces an increasing number of spikes at an increasing frequency in neocortical neurons during the first few stimuli. Possible mechanisms underlying these cortical augmenting responses were analyzed with a computer model that included populations of thalamocortical cells, thalamic reticular neurons, up to two layers of cortical pyramidal cells, and cortical inhibitory interneurons. Repetitive thalamic stimulation produced a low-threshold intrathalamic augmentation in the model based on the deinactivation of the low-threshold Ca2+ current in thalamocortical cells, which in turn induced cortical augmenting responses. In the cortical model, augmenting responses were more powerful in the "input" layer compared with those in the "output" layer. Cortical stimulation of the network model produced augmenting responses in cortical neurons in distant cortical areas through corticothalamocortical loops and low-threshold intrathalamic augmentation. Thalamic stimulation was more effective in eliciting augmenting responses than cortical stimulation. Intracortical inhibition had an important influence on the genesis of augmenting responses in cortical neurons: A shift in the balance between intracortical excitation and inhibition toward excitation transformed an augmenting responses to long-lasting paroxysmal discharge. The predictions of the model were compared with in vivo recordings from neurons in cortical area 4 and thalamic ventrolateral nucleus of anesthetized cats. The known intrinsic properties of thalamic cells and thalamocortical interconnections can account for the basic properties of cortical augmenting responses.