Horizontal spread of synchronized activity in neocortex and its control by GABA-mediated inhibition

1989 ◽  
Vol 61 (4) ◽  
pp. 747-758 ◽  
Author(s):  
Y. Chagnac-Amitai ◽  
B. W. Connors
Keyword(s):  
Neural Activity ◽  
Single Cells ◽  
Epileptiform Activity ◽  
Cortical Activity ◽  
Synaptic Activity ◽  
Cortical Inhibition ◽  
Field Potentials ◽  
Bathing Medium ◽  
Horizontal Spread ◽  
Epileptiform Events

1. Suppression of GABAA receptor-mediated inhibition disrupts the neural activity of neocortex and can lead to synchronized discharges that mimic those of partial epilepsy. We have studied the role of GABAA-mediated inhibition in controlling the synchronization and horizontal (tangential) spread of cortical activity. 2. Slices of rat SmI were maintained in vitro and focally stimulated in layer VI while recording with a horizontal array of extracellular electrodes. Inhibition was slightly suppressed by adding low concentrations of the GABAA antagonists bicuculline or bicuculline methiodide to the bathing medium. Under control conditions neural activity was narrowly confined to a vertical strip of cortex. The horizontal spread of activity expanded about twofold in the presence of antagonist concentrations (less than or equal to 0.5 microM) that were expected to suppress GABAA function by no more than 10-20%. 3. At antagonist concentrations between 0.4 and 1.0 microM, evoked epileptiform activity appeared. These threshold-dose epileptiform events showed wide variations in size and duration (even at the same recording site), very variable distances of horizontal propagation, specific sites of propagation failure, reversals of propagation direction, and directional asymmetries in their probability of propagation. This contrasts with activity observed previously (Ref. 9) in high bicuculline concentrations (greater than or equal to 10 microM): large, stereotyped events that propagate reliably without decrement or reflection. 4. Intracellular recordings were obtained from pyramidal neurons in layers II/III in the presence of less than or equal to 1 microM bicuculline. Inhibitory postsynaptic potentials (IPSPs) were observed during both primary evoked responses and propagating epileptiform events and were often comparable in size and duration to those in untreated cortex. Epileptiform field potentials were always correlated with synaptic activity in single cells, but the pattern and type of PSPs varied with the form of the field potentials. Large amplitude epileptiform events coincided with an overwhelming inhibition of upper layer neurons. 5. We conclude that 1) the horizontal spread of normal cortical activity is strongly constrained by GABAA-mediated IPSPs, 2) a relatively small reduction in the efficacy of inhibition leads to a large increase in the spread of excitation, 3) initiation and propagation of synchronized epileptiform activity can occur even in the presence of robust cortical inhibition, and 4) the character of epileptiform activity is strongly affected by the influences of inhibition.

scholarly journals Prefrontal cortical plasticity during learning of cognitive tasks

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Hua Tang ◽  
Mitchell R. Riley ◽  
Balbir Singh ◽  
Xue-Lian Qi ◽  
David T. Blake ◽  
...  
Keyword(s):  
Neural Activity ◽  
Cortical Plasticity ◽  
Cortical Activity ◽  
Phase Changes ◽  
Cognitive Tasks ◽  
Training Phase ◽  
Field Potentials ◽  
Electrode Arrays ◽  
Control Task ◽  
Prefrontal Cortical

AbstractTraining in working memory tasks is associated with lasting changes in prefrontal cortical activity. To assess the neural activity changes induced by training, we recorded single units, multi-unit activity (MUA) and local field potentials (LFP) with chronic electrode arrays implanted in the prefrontal cortex of two monkeys, throughout the period they were trained to perform cognitive tasks. Mastering different task phases was associated with distinct changes in neural activity, which included recruitment of larger numbers of neurons, increases or decreases of their firing rate, changes in the correlation structure between neurons, and redistribution of power across LFP frequency bands. In every training phase, changes induced by the actively learned task were also observed in a control task, which remained the same across the training period. Our results reveal how learning to perform cognitive tasks induces plasticity of prefrontal cortical activity, and how activity changes may generalize between tasks.

Synchronized excitation and inhibition driven by intrinsically bursting neurons in neocortex

1989 ◽  
Vol 62 (5) ◽  
pp. 1149-1162 ◽  
Author(s):  
Y. Chagnac-Amitai ◽  
B. W. Connors
Keyword(s):  
Action Potentials ◽  
Lower Layer ◽  
Single Cells ◽  
Pyramidal Cells ◽  
Synaptic Activity ◽  
Large Field ◽  
Repetitive Firing ◽  
Field Potentials ◽  
Single Neurons ◽  
Single Action

1. The cellular mechanisms of synchronous synaptic activity were studied in isolated slices of rat SmI neocortex in which gamma-aminobutyric acid (GABA)-mediated inhibition was slightly suppressed. Intracellular measurements were made from single neurons, and extracellular recordings monitored the timing and intensity of population events. 2. Neurons in cortical layers II-VI were classified by the attributes of their single action potentials and repetitive firing patterns during injection of intracellular current pulses. Regular-spiking (RS) cells occurred in all layers and had relatively long-duration spikes and strong frequency adaptation. Intrinsically bursting (IB) cells occurred only in layers IV and V and generated bursts of greater than or equal to 3 spikes; some IB cells of lower-layer V produced repetitive bursts during long depolarizing pulses. Fast-spiking (FS) cells had brief spikes and little or no adaptation and fired at high frequencies. 3. When GABAA-mediated inhibition was slightly reduced with low doses of bicuculline methiodide (BMI, 0.8-1.0 microM), synchronous events were evoked by stimulating layer VI with single shocks. Synchronous events were characterized by prominent, often all-or-none extracellular field potentials that propagated horizontally for variable distances up to several millimeters. Large field potentials were invariably correlated with excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) in single neurons. Both PSPs and field potentials often had long (up to 250 ms) and variable latencies, and sometimes two or more events were generated by single stimuli. In all cases the PSPs and field potentials were synchronous. Both field potentials and single cells sometimes generated short epochs (3-7 peaks) of rhythmic events at 20-50 Hz. 4. The physiological class of single neurons was correlated with the relative dominance of excitation and inhibition during each synchronous event. In phase with each synchronous event, most RS cells were very strongly inhibited with only small amounts of concurrent excitation. By contrast, IB cells were strongly and consistently excited, with relatively little inhibition. FS cells were also phasically excited. 5. Anatomic studies have identified RS and IB cells as pyramidal cells and FS cells as GABAergic nonpyramidal cells. This implies that, during the synchronous events of the present study, the majority of pyramidal cells were dominated by IPSPs. Synchronous excitation of FS cells, the presumed inhibitory interneurons, is consistent with this. Only a subset of the pyramidal neurons, almost all of them IB cells of the middle layers, displayed strong, synchronous excitation and clusters of action potentials.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Bidirectional neuron-glioma interactions: effects of glioma cells on synaptic activity and its impact on tumor growth

2019 ◽  
Vol 21 (Supplement_4) ◽  
pp. iv1-iv1
Author(s):  
Elena Tantillo ◽  
Eleonora Vannini ◽  
Chiara Cerri ◽  
Chiara Maria Mazzanti ◽  
Mario Costa ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Neural Activity ◽  
Visual Stimulation ◽  
Glioma Cells ◽  
Cortical Activity ◽  
Synaptic Function ◽  
Synaptic Activity ◽  
Network Activity ◽  
Functional Changes ◽  
Glioma Progression

Abstract Gliomas grow in a neuronal environment, but little is known on the functional changes in peritumoral neurons during tumor development. Moreover, investigations on the role of neural activity in glioma progression have yielded contradictory results. Here, we monitored longitudinal changes in network activity by recording visual evoked potentials (VEP) and local field potentials (LFP) after transplant of GL261 glioma cells in mouse visual cortex. We detected a progressive deterioration of VEP amplitudes in glioma-bearing mice, accompanied by an increase in slow network oscillations. At the cellular level, the analysis of microdissected peritumoral neurons showed alterations in both pre- and post-synaptic markers. To investigate whether glioma-driven alterations in synaptic function may impact on tumor growth, we manipulated levels of afferent cortical activity in glioma-bearing mice. Specifically, we tested blockade of synaptic activity via botulinum neurotoxin A (BoNT/A), visual deprivation (dark rearing, DR) and visual stimulation (VS). Replicating cells were quantified via immunostaining for BrdU and Ki67. We found that manipulation of cortical activity bidirectionally regulated glioma proliferation. Silencing of cortical synapses with BoNT/A and DR increased tumor proliferation while daily VS had the opposite effect. These findings demonstrate reduced responsiveness of peritumoral neurons which may in turn stimulate tumor cell proliferation, thus triggering a vicious loop that exacerbates glioma progression. Physiological stimulation of neural activity appears to restrain glioma proliferation so it could be implemented in the clinical setting as an adjuvant therapy.

Eyeblink conditioning contingent on hippocampal theta enhances hippocampal and medial prefrontal responses

2011 ◽  
Vol 105 (5) ◽  
pp. 2213-2224 ◽  
Author(s):  
Ryan D. Darling ◽  
Kanako Takatsuki ◽  
Amy L. Griffin ◽  
Stephen D. Berry
Keyword(s):  
Neural Activity ◽  
Theta Rhythm ◽  
Eyeblink Conditioning ◽  
Trace Conditioning ◽  
Distributed Network ◽  
Field Potentials ◽  
Trace Interval ◽  
Behavioral Learning ◽  
Paired Group ◽  
Hippocampal Theta

Trace eyeblink classical conditioning (tEBCC) can be accelerated by making training trials contingent on the naturally generated hippocampal 3- to 7-Hz theta rhythm. However, it is not well-understood how the presence (or absence) of theta affects stimulus-driven changes within the hippocampus and how it correlates with patterns of neural activity in other essential trace conditioning structures, such as the medial prefrontal cortex (mPFC). In the present study, a brain-computer interface delivered paired or unpaired conditioning trials to rabbits during the explicit presence (T+) or absence (T−) of theta, yielding significantly faster behavioral learning in the T+-paired group. The stimulus-elicited hippocampal unit responses were larger and more rhythmic in the T+-paired group. This facilitation of unit responses was complemented by differences in the hippocampal local field potentials (LFP), with the T+-paired group demonstrating more coherent stimulus-evoked theta than T−-paired animals and both unpaired groups. mPFC unit responses in the rapid learning T+-paired group displayed a clear inhibitory/excitatory sequential pattern of response to the tone that was not seen in any other group. Furthermore, sustained mPFC unit excitation continued through the trace interval in T+animals but not in T−animals. Thus theta-contingent training is accompanied by 1) acceleration in behavioral learning, 2) enhancement of the hippocampal unit and LFP responses, and 3) enhancement of mPFC unit responses. Together, these data provide evidence that pretrial hippocampal state is related to enhanced neural activity in critical structures of the distributed network supporting the acquisition of tEBCC.

scholarly journals Potassium diffusive coupling in neural networks

2010 ◽  
Vol 365 (1551) ◽  
pp. 2347-2362 ◽  
Author(s):  
Dominique M. Durand ◽  
Eun-Hyoung Park ◽  
Alicia L. Jensen
Keyword(s):  
Neural Networks ◽  
Neural Activity ◽  
Neuronal Excitability ◽  
Epileptiform Activity ◽  
Lateral Diffusion ◽  
Normal Activity ◽  
Ionic Concentration ◽  
Extracellular Potassium ◽  
Potassium Accumulation ◽  
Diffusive Coupling

Conventional neural networks are characterized by many neurons coupled together through synapses. The activity, synchronization, plasticity and excitability of the network are then controlled by its synaptic connectivity. Neurons are surrounded by an extracellular space whereby fluctuations in specific ionic concentration can modulate neuronal excitability. Extracellular concentrations of potassium ([K + ] o ) can generate neuronal hyperexcitability. Yet, after many years of research, it is still unknown whether an elevation of potassium is the cause or the result of the generation, propagation and synchronization of epileptiform activity. An elevation of potassium in neural tissue can be characterized by dispersion (global elevation of potassium) and lateral diffusion (local spatial gradients). Both experimental and computational studies have shown that lateral diffusion is involved in the generation and the propagation of neural activity in diffusively coupled networks. Therefore, diffusion-based coupling by potassium can play an important role in neural networks and it is reviewed in four sections. Section 2 shows that potassium diffusion is responsible for the synchronization of activity across a mechanical cut in the tissue. A computer model of diffusive coupling shows that potassium diffusion can mediate communication between cells and generate abnormal and/or periodic activity in small (§3) and in large networks of cells (§4). Finally, in §5, a study of the role of extracellular potassium in the propagation of axonal signals shows that elevated potassium concentration can block the propagation of neural activity in axonal pathways. Taken together, these results indicate that potassium accumulation and diffusion can interfere with normal activity and generate abnormal activity in neural networks.

Altered desensitization produces enhancement of EPSPs in neocortical neurons

1994 ◽  
Vol 72 (2) ◽  
pp. 1032-1036 ◽  
Author(s):  
M. R. Pelletier ◽  
J. J. Hablitz
Keyword(s):  
Nmda Receptors ◽  
Time Course ◽  
Glutamate Release ◽  
Epileptiform Activity ◽  
Brain Slices ◽  
Synaptic Activity ◽  
Membrane Properties ◽  
Repetitive Firing ◽  
Resting Membrane Potential ◽  
Bath Application

1. Neocortical brain slices were prepared from rats (35–50 days of age) and maintained in vitro. Intracellular recordings were obtained from neurons in cortical layers II/III. The effect of bath application of cyclothiazide (CYZ), a potent blocker of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor desensitization, on evoked synaptic activity and passive membrane properties was investigated. 2. Bath application of CYZ did not significantly affect resting membrane potential, input resistance, or repetitive firing. CYZ increased both the amplitude and duration of evoked excitatory postsynaptic potentials (EPSPs). Polysynaptic responses were also augumented. These effects persisted after the blockade of N-methyl-D-aspartate (NMDA) receptors with D-2-amino-5-phosphonovaleric acid (D-APV). The magnitude of these effects appeared to vary directly with stimulation intensity and presumably, amount of glutamate release. 3. Epileptiform activity was induced by bath application of bicuculline methiodide. The amplitude and duration of evoked paroxysmal discharges were increased by CYZ. Similar results were seen in presence of D-APV. 4. These results indicate that CYZ has significant effects on synaptic transmission. Desensitization of non-NMDA receptors may be an important mechanism for determining the time course of EPSPs and in curtailing epileptiform responses in the rat neocortex.

scholarly journals The Making of Long-Lasting Memories: A Fruit Fly Perspective

2021 ◽  
Vol 15 ◽  
Author(s):  
Camilla Roselli ◽  
Mani Ramaswami ◽  
Tamara Boto ◽  
Isaac Cervantes-Sandoval
Keyword(s):  
Learning And Memory ◽  
Neural Activity ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Fruit Fly ◽  
Memory Formation ◽  
Synaptic Activity ◽  
Model Organisms ◽  
Transient Wave ◽  
Control Of Gene Expression

Understanding the nature of the molecular mechanisms underlying memory formation, consolidation, and forgetting are some of the fascinating questions in modern neuroscience. The encoding, stabilization and elimination of memories, rely on the structural reorganization of synapses. These changes will enable the facilitation or depression of neural activity in response to the acquisition of new information. In other words, these changes affect the weight of specific nodes within a neural network. We know that these plastic reorganizations require de novo protein synthesis in the context of Long-term memory (LTM). This process depends on neural activity triggered by the learned experience. The use of model organisms like Drosophila melanogaster has been proven essential for advancing our knowledge in the field of neuroscience. Flies offer an optimal combination of a more straightforward nervous system, composed of a limited number of cells, and while still displaying complex behaviors. Studies in Drosophila neuroscience, which expanded over several decades, have been critical for understanding the cellular and molecular mechanisms leading to the synaptic and behavioral plasticity occurring in the context of learning and memory. This is possible thanks to sophisticated technical approaches that enable precise control of gene expression in the fruit fly as well as neural manipulation, like chemogenetics, thermogenetics, or optogenetics. The search for the identity of genes expressed as a result of memory acquisition has been an active interest since the origins of behavioral genetics. From screenings of more or less specific candidates to broader studies based on transcriptome analysis, our understanding of the genetic control behind LTM has expanded exponentially in the past years. Here we review recent literature regarding how the formation of memories induces a rapid, extensive and, in many cases, transient wave of transcriptional activity. After a consolidation period, transcriptome changes seem more stable and likely represent the synthesis of new proteins. The complexity of the circuitry involved in memory formation and consolidation is such that there are localized changes in neural activity, both regarding temporal dynamics and the nature of neurons and subcellular locations affected, hence inducing specific temporal and localized changes in protein expression. Different types of neurons are recruited at different times into memory traces. In LTM, the synthesis of new proteins is required in specific subsets of cells. This de novo translation can take place in the somatic cytoplasm and/or locally in distinct zones of compartmentalized synaptic activity, depending on the nature of the proteins and the plasticity-inducing processes that occur. We will also review recent advances in understanding how localized changes are confined to the relevant synapse. These recent studies have led to exciting discoveries regarding proteins that were not previously involved in learning and memory processes. This invaluable information will lead to future functional studies on the roles that hundreds of new molecular actors play in modulating neural activity.

scholarly journals Cross-modal orienting of exogenous attention results in visual-cortical facilitation, not suppression

2020 ◽  
Author(s):  
Jonathan M. Keefe ◽  
Emilia Pokta ◽  
Viola S. Störmer
Keyword(s):  
Neural Activity ◽  
Target Location ◽  
Visual Target ◽  
Cortical Activity ◽  
Exogenous Attention ◽  
Peripheral Target ◽  
Behavioral Performance ◽  
Auditory Cue ◽  
Visual Cortical

AbstractAttention may be oriented exogenously (i.e., involuntarily) to the location of salient stimuli, resulting in improved perception. However, it is unknown whether exogenous attention improves perception by facilitating processing of attended information, suppressing processing of unattended information, or both. To test this question, we measured behavioral performance and cue-elicited neural changes in the electroencephalogram as participants (N = 19) performed a task in which a spatially non-predictive auditory cue preceded a visual target. Critically, this cue was either presented at a peripheral target location or from the center of the screen, allowing us to isolate spatially specific attentional activity. We find that both behavior and attention-mediated changes in visual-cortical activity are enhanced at the location of a cue prior to the onset of a target, but that behavior and neural activity at an unattended target location are equivalent to that following a central cue that does not direct attention (i.e., baseline). These results suggest that exogenous attention operates solely via facilitation of information at an attended location.

scholarly journals Key aspects of neurovascular control mediated by specific populations of inhibitory cortical interneurons

2019 ◽  
Author(s):  
L Lee ◽  
L Boorman ◽  
E Glendenning ◽  
C Christmas ◽  
P Sharp ◽  
...  
Keyword(s):  
Neural Activity ◽  
Cortical Inhibition ◽  
Cortical Interneurons ◽  
Haemodynamic Changes ◽  
A Cell ◽  
Cortical Excitation ◽  
Negative Bold ◽  
Key Aspects ◽  
Oxide Synthase

AbstractInhibitory interneurons can evoke vasodilation and vasoconstriction, making them potential cellular drivers of neurovascular coupling. However, the specific regulatory roles played by particular interneuron subpopulations remain unclear. Our purpose was therefore to adopt a cell-specific optogenetic approach to investigate how somatostatin (SST) and neuronal nitric oxide synthase (NOS1)-expressing interneurons might influence neurovascular relationships. In mice, specific activation of SST- or NOS1-interneurons was sufficient to evoke haemodynamic changes similar to those evoked by physiological whisker stimulation. In the case of NOS1-interneurons, robust haemodynamic changes occurred with minimal changes in neural activity. Conversely, activation of SST-interneurons produced robust changes in evoked neural activity with shallow cortical excitation and pronounced deep layer cortical inhibition. This often resulted in a central increase in blood volume with corresponding surround decrease, analogous to the negative BOLD signal. These results demonstrate the role of specific populations of cortical interneurons in the active control of neurovascular function.

Initiation of Spontaneous Epileptiform Activity in the Neocortical Slice

1998 ◽  
Vol 80 (2) ◽  
pp. 978-982 ◽  
Author(s):  
Yang Tsau ◽  
Li Guan ◽  
Jian-Young Wu
Keyword(s):  
Optical Imaging ◽  
Epileptiform Activity ◽  
Fast Imaging ◽  
Dominant Focus ◽  
Adult Rat ◽  
Neocortical Slice ◽  
Local Circuitry ◽  
Multielectrode Recording ◽  
Voltage Sensitive Dyes ◽  
Epileptiform Events

Tsau, Yang, Li Guan, and Jian-Young Wu. Initiation of spontaneous epileptiform activity in the neocortical slice. J. Neurophysiol. 80: 978–982, 1998. Cortical local circuitry is important in epileptogenesis. Voltage-sensitive dyes and fast imaging were used to visualize the initiation of spontaneous paroxysmal events in adult rat neocortical slices. Although spontaneous paroxysmal events could start from anywhere in the preparation, optical imaging revealed that all spontaneous events started at a few confined initiation foci and propagated to the whole preparation. Multielectrode recording over hundreds of spontaneous events revealed that often two or three initiation foci coexisted in each preparation ( n = 10). These foci took turns being dominant; the dominant focus initiated the majority of the spontaneous paroxysmal events during that period. The dominant focus and dynamic rearrangement of foci suggest that the initiation of spontaneous epileptiform events involves a local multineuronal process, perhaps with potentiated synapses.

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