995 research outputs found
Feature selectivity of the gamma-band of the local field potential in primate primary visual cortex
No full textExtra-cellular voltage fluctuations (local field potentials; LFPs) reflecting neural mass action are ubiquitous across species and brain regions. Numerous studies have characterized the properties of LFP signals in the cortex to study sensory and motor computations as well as cognitive processes like attention, perception and memory. In addition, its extracranial counterpart – the electroencelphalogram (EEG) – is widely used in clinical applications. However, the link between LFP signals and the underlying activity of local populations of neurons remains largely elusive. Here, we review recent work elucidating the relationship between spiking activity of local neural populations and LFP signals. We focus on oscillations in the gamma-band (30-90Hz) of the local field potential in the primary visual cortex (V1) of the macaque that dominate during visual stimulation. Given that in area V1 much is known about the properties of single neurons and the cortical architecture, it provides an excellent opportunity to study the mechanisms underlying the generation of the local field potential
Orientation tuning of the local field potential and multi-unit activity in the primary visual cortex of the macaque
No full textOscillations in the local field potential (LFP) are abundant across species and brain regions. The possible relationship of these low-frequency extracelluar voltage fluctuations with the activity of the underlying local population of neurons remains largely elusive. To study this relationship, we used an array of chronically implanted tetrodes spanning a distance of 700 μm and simultaneously recorded action potentials from multiple well-isolated single units, multi unit activity (MUA) and LFP from area V1 of the awake, behaving macaque. Moving and static gratings of different orientations were used for visual stimulation. In agreement with previous studies we find that the increase of LFP gamma-band power is a function of the orientation of the stimulus. However, the power of the gamma-band contains much less information about the orientation of the stimulus than the MUA and SUA recorded at the same site (Figure 1A). The average discriminability d‘ between preferred and orthogonal orientation was 2.46 for MUA, 2.45 for SUA and 1.01 for the LFP. Moreover, in contrast to recent results from area MT (Liu and Newsome, 2006) we find only a weak correlation between the preferred orientation of the MUA tuning function and that of the LFP (Figure 1B, different colors indicate different animals). Interestingly, all nearby LFP recording sites in our array were tuned to a similar orientation while the preferred orientations of MUA tuning functions were widely scattered. These results suggest that the power of LFP signals does not capture local population activity at the scale of orientation columns in area V1
Decorrelated Neuronal Firing in Cortical Microcircuits
No full textCorrelated trial-to-trial variability in the activity of cortical neurons is thought to reflect the functional connectivity of the circuit. Many cortical areas are organized into functional columns, in which neurons are believed to be densely connected and to share common input. Numerous studies report a high degree of correlated variability between nearby cells. We developed chronically implanted multitetrode arrays offering unprecedented recording quality to reexamine this question in the primary visual cortex of awake macaques. We found that even nearby neurons with similar orientation tuning show virtually no correlated variability. Our findings suggest a refinement of current models of cortical microcircuit architecture and function: Either adjacent neurons share only a few percent of their inputs or, alternatively, their activity is actively decorrelated
Orientation tuning of the local field potential and multi-unit activity in the primary visual cortex of the macaque
No full textOscillations in the local field potential (LFP) are abundant across species and brain regions. The possible relationship of these low-frequency extracelluar voltage fluctuations with the activity of the underlying local population of neurons remains largely elusive. To study this relationship, we used an array of chronically implanted tetrodes spanning a distance of 700 μm and simultaneously recorded action potentials from multiple well-isolated single units, multi unit activity (MUA) and LFP from area V1 of the awake, behaving macaque. Moving and static gratings of different orientations were used for visual stimulation. In agreement with previous studies we find that the increase of LFP gamma-band power is a function of the orientation of the stimulus. However, the power of the gamma-band contains much less information about the orientation of the stimulus than the MUA and SUA recorded at the same site (Figure 1A). The average discriminability d ‘between preferred and orthogonal orientation was 2.46 for MUA, 2.45 for SUA and 1.01 for the LFP. Moreover, in contrast to recent results from area MT (Liu and Newsome, 2006) we find only a weak correlation between the preferred orientation of the MUA tuning function and that of the LFP (Figure 1B, different colors indicate different animals). Interestingly, all nearby LFP recording sites in our array were tuned to a similar orientation while the preferred orientations of MUA tuning functions were widely scattered. These results suggest that the power of LFP signals does not capture local population activity at the scale of orientation columns in area V1
Comparing the feature selectivity of the gamma-band of the local field potential and the underlying spiking activity in primate visual cortex
No full textThe local field potential (LFP), comprised of low-frequency extra-cellular voltage fluctuations, has been used extensively to study the mechanisms of brain function. In particular, oscillations in the gamma-band (30–90 Hz) are ubiquitous in the cortex of many species during various cognitive processes. Surprisingly little is known about the underlying biophysical processes generating this signal. Here, we examine the relationship of the local field potential to the activity of localized populations of neurons by simultaneously recording spiking activity and LFP from the primary visual cortex (V1) of awake, behaving macaques. The spatial organization of orientation tuning and ocular dominance in this area provides an excellent opportunity to study this question, because orientation tuning is organized at a scale around one order of magnitude finer than the size of ocular dominance columns. While we find a surprisingly weak correlation between the preferred orientation of multi-unit activity and gamma-band LFP recorded on the same tetrode, there is a strong correlation between the ocular preferences of both signals. Given the spatial arrangement of orientation tuning and ocular dominance, this leads us to conclude that the gamma-band of the LFP seems to sample an area considerably larger than orientation columns. Rather, its spatial resolution lies at the scale of ocular dominance columns
Recording Chronically from the same Neurons in Awake, Behaving Primates
No full textUnderstanding the mechanisms of learning requires characterizing how the response properties of individual neurons and interactions across populations of neurons change over time. In order to study learning in-vivo, we need the ability to track an electrophysiological signature that uniquely identifies each recorded neuron for extended periods of time. We have identified such an extracellular signature using a statistical framework which allows quantification of the accuracy by which stable neurons can be identified across successive recording sessions. Our statistical framework uses spike waveform information recorded on a tetrodes four channels in order to define a measure of similarity between neurons recorded across time. We use this framework to quantitatively demonstrate for the first time the ability to record from the same neurons across multiple consecutive days and weeks. The chronic recording techniques and methods of analyses we report can be used to characterize the changes in brain circuits du
e to learning
Unraveling the interplay of brain networks by combining neuromodulatory tools and in vivo MRI in rodents
No full textAbstract: The increasing prevalence of neurological disorders poses an ever-increasing healthcare burden on society. A better understanding of the underlying mechanisms mediating these neurological disorders is indispensable for the identification of new potential therapeutic targets. Various neurological disorders have been associated with disturbances in the interplay of functional brain networks. This thesis focuses on unraveling the relationships between functional brain networks, with particular interest for the default mode-like network and task-positive networks in rodents. We utilized a relatively new multi-modal approach combining chemogenetics and non-invasive functional magnetic resonance imaging (fMRI). This combined approach allows collecting valuable information about the role of specific subsets of cells in brain network function and dysfunction. In the first part of this thesis, we found that chemogenetic manipulation of a specific area, i.e. the anterior cingulate area (ACC), is able to modulate the neural activity and functional connectivity of brain networks. More specifically, silencing of the ACC resulted in altered neural activity and functional connectivity in brain networks including connections with sensory cortex, thalamus, basolateral amygdala and ventral pallidum, areas involved in attention processes, working memory, fear behavior and reward, respectively. In addition, we found that damage to the ACC is associated with decreased functional connectivity in the default mode-like network, the task-positive network and visual system. Interestingly, these affected functional networks demonstrated distinguishable recovery patterns over time. In the second part of this thesis, we focused on the interactions between the default mode-like network and attentional processes. We found that stimulating bottom-up sensory processes (by presenting continuous random flickering light to sedated rats) could decrease the activity and functional connectivity in the default mode-like network, similarly as task-related deactivations. In a next study, we aimed to shed light on the mechanisms involved in the deactivation of the default mode-like network during attentional processes. Our results indicated functional connectivity decreases in the default mode-like network upon chemogenetic stimulation of basal forebrain cholinergic neurons, suggesting a role for the cholinergic system in default mode-like network regulation. Taken together, this thesis provides unique insights on functional and dysfunctional brain networks. Furthermore, this thesis underscores the significance of combining chemogenetics with fMRI for future studies as well as its promise for future neurotherapeutics as it can eliminate the off-target effects of current therapeutics and allows the on-demand control of specified neurons
Der griechische Gelehrte Georgios Zachariadis und sein Beitrag zum slawischen Schrifttum im 19. Jahrhundert
No full textAmong the Greek scholars who lived during the 19th century in the north-eastern Balkans, and also in Central Europe, and by their work contributed to the spiritual development of the Balkan Slavs, pride of place must be given to Georgios Zachariadis. Unfortunately, however, no detailed monograph on Zachariadis exists. On this account the problems that arise concerning the life and activities of this Greek scholar are still many and varied. In his study the author tries to fill one part of this lacuna. At the beginning of the work the following are examined, on the basis of new historical evidence: the date and place of Georgios Zachariadis’ birth, his studies and tenure as teacher in the Greek school at Zemun, the Serbian school at Šabac, and the Greek school in Vienna. The author continues his study by analyzing the various works of Zachariadis, which are written on Old Church^Slavonic, and the translations this Greek scholar made from Greek into Old Church Slavonic. Finally, the extent of Georgios Zachariadis’ contribution to Slavonic letters is made clear
Unravelling the impacts of misfolded proteins in the initiation and progression of Alzheimer's disease
No full textAbstract: Alzheimer\u2019s disease (AD) is an incurable neurodegenerative disorder, eventually leading to dementia and affecting the elderly. Due to ageing of the population, the prevalence of AD is expected to rise, with a global cost of caretaking of AD patients estimated to hundreds of billion dollars. As the aetiology of AD pathology remains elusive, the development of appropriate curative therapies requires more in-depth knowledge on the early stages of AD pathology, which is the focus of this PhD. We studied the impacts of misfolded proteins encountered in AD (A\u3b2, tau) in the initiation and progression of AD pathology, using highly translational in vivo MRI techniques, in combination with the Tet-Off APP and hTau.P301L mouse models, simulating A\u3b2 and tau pathology, respectively, in a context resembling sporadic AD. On the one hand, the Tet-Off APP mice showed early soluble A\u3b2-associated hyperconnectivity of brain networks prior to A\u3b2 plaque formation, followed by a hypoconnectivity after the onset of A\u3b2 plaque deposition which was associated with neuroinflammation surrounding the plaques. Furthermore, the effects of A\u3b2 accumulation on the brain-wide glymphatic clearance were evaluated at a more advanced stage of AD and showed an impaired glymphatic brain fluid transport. More specifically, they demonstrated a reduced glymphatic inflow in the brain parenchyma affecting the dynamics of the glymphatic transport and thus presumably the effective clearance of brain waste, including A\u3b2. On the other hand, in the hTau.P301L mice, tau fibrils did not affect the functional connectivity of brain networks, despite progressive accumulation throughout the brain up to 15 weeks after seeding. In conclusion, the results presented in this thesis indicate that degradation of the brain\u2019s functional integrity is associated with soluble A\u3b2 toxicity, even in a context of sporadic AD. Moreover, A\u3b2 toxicity seems to also impact the glymphatic brain fluid circulation directly and indirectly in AD pathology, with a brain-wide spread of neuroinflammatory responses. This demonstrates as well the importance of using neuroimaging techniques to shed light on the underlying mechanisms of the early events caused by the synergy between A\u3b2 and tau, emphasizing the clinical relevance of preclinical studies using animal models, especially for the identification of new targets, as potential therapeutic strategies for AD
The influence of different brain states on the default mode-like network in rodents
No full textAbstract: The default mode network (DMN) is a large-scale brain network that is thought to play a fundamental role in internally oriented cognition, self-referential thought, mind-wandering and autobiographical memory. This brain network has consistently been shown in humans to be highly active and synchronized during rest. However, during an attentive brain state, e.g. during the performance of an external attention demanding task, DMN deactivates and desynchronizes. This functionality of the DMN is thought to facilitate task performance by suppressing internally based processing and task-independent brain activity during a task. Furthermore, it allows to shift additional cognitive processing resources towards the execution of the task. In recent years, preclinical imaging studies have discovered the existence of a default mode-like network (DMLN) in rodents. This DMLN consist out of anatomical homologous regions to the DMN in humans, however the resemblance in functionality remains to be proven. In this thesis, we investigated the functionality of the DMLN in rodents by using functional magnetic resonance imaging (fMRI) techniques during a visual attentive brain state. Here we could demonstrate that similarly as the human DMN, DMLN in rats was shown to deactivate and desynchronize during a visual attentive brain state. This result provides evidence that DMLN in rodents is functionally alike to the DMN in humans. As both networks show high correspondence in anatomy and functionality, results coming from DMLN animal studies could aid to some extent in the understanding of the DMN in humans. Next, we investigated a potential mechanism through which attention might modulate the DMLN i.e. the cholinergic system. As such, we used chemogenetics to stimulate cholinergic neurons in the basal forebrain inducing a cholinergic stimulated brain state and its effect was investigated using fMRI techniques. Results coming from this experiment demonstrated a clear roll of the cholinergic system in the control of synchronization and activity of the DMLN. Due to the strong link between attention and the cholinergic system, we hypothesize that the cholinergic system is the neuromodulatory system through which the attention system exert its modulation on the DMLN. Lastly, in the final part of the thesis, we focused on improving analysis methods for fMRI techniques. To do so, we developed a probabilistic vascular mouse brain atlas to objectively detect vascular influences within fMRI data. The vascular atlas was applied to fMRI data and was demonstrated to be an effective method to objectively identify vascular influences
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