Suppression Of Neural Activity Research Articles

Age-related differences in enhancement and suppression of neural activity underlying selective attention in matched young and old adults

Selective attention reflects the top-down control of sensory processing that is mediated by enhancement or inhibition of neural activity. ERPs were used to investigate age-related differences in neural activity in an experiment examining selective attention to color under Attend and Ignore conditions, as well as under a Neutral condition in which color was task-irrelevant. We sought to determine whether differences in neural activity between old and young adult subjects were due to differences in age rather than executive capacity. Old subjects were matched to two groups of young subjects on the basis of neuropsychological test performance: one using age-appropriate norms and the other using test scores not adjusted for age. We found that old and young subject groups did not differ in the overall modulation of selective attention between Attend and Ignore conditions, as indexed by the size of the anterior Selection Positivity. However, in contrast to either young adult group, old subjects did not exhibit reduced neural activity under the Ignore relative to Neutral condition, but showed enhanced activity under the Attend condition. The onset and peak of the Selection Positivity occurred later for old than young subjects. In summary, older adults execute selective attention less efficiently than matched younger subjects, with slowed processing and failed suppression under Ignore. Increased enhancement under Attend may serve as a compensatory mechanism.

General Anesthesia

Appropriate balance between excitatory and inhibitory neural activity patterns is of utmost importance in the maintenance of neuronal homeostasis. General anesthetic-induced pharmacological interference with this equilibrium results not only in a temporary loss of consciousness but can also initiate long-term changes in brain function. Although these alterations were initially considered deleterious, recent observations suggest that at least under some specific conditions, they may eventually improve neural function. The goal of this review is to provide insights into the mechanisms underlying these dual effects. Basic science issues on the important role of critical periods during neural circuitry assembly will be discussed to better understand how even brief exposures to general anesthetics could initiate context-dependent lasting changes in neuronal structure and function. Recent series of observations suggesting a developmental stage-dependent impact of these drugs on synaptogenesis will then be summarized together with currently known molecular mechanisms underlying these effects. Particular emphasis will be placed on how anesthetic drugs modulate neural plasticity in the adult brain and how this may improve neural function under some pathological states. The ensemble of these new observations strongly suggests that general anesthetics should not merely be considered toxic drugs but rather acknowledged as robust, context-dependent modulators of neural plasticity.

Low-Level Right Vagal Stimulation: Anticholinergic and Antiadrenergic Effects

We sought to extend the use of low-level vagal stimulation by applying it only to the right vagus nerve (LL-RVS) to suppress atrial fibrillation (AF). In 10 pentobarbital anesthetized dogs, LL-RVS (20 Hz, 0.1 ms pulse width) was delivered to the right vagal trunk via wire electrodes at voltages 50% below that which slowed the sinus rate (SR) or atrio-ventricular conduction. Electrode catheters were sutured at multiple atrial and pulmonary vein (PV) sites to record electrograms. LL-RVS continued for 3 hours. At the end of each hour, 40 ms of high-frequency stimulation (HFS; 100 Hz, 0.01 ms pulse width) was delivered 2 ms after atrial pacing (during the refractory period) to determine the AF threshold (AF-TH) at each site. Other electrodes were attached to the superior left ganglionated plexi (SLGP) and right stellate ganglion (RSG) so that HFS (20 Hz, 0.1 ms pulse width) to these sites induced SR slowing and acceleration, respectively. Microelectrodes inserted into the anterior right ganglionated plexi (ARGP) recorded neural activity. (1) Three hours of LL-RVS induced a progressive increase in AF-TH at all sites (all P < 0.05). (2) The SR slowing and acceleration response induced by SLGP and RSG stimulation, respectively, was blunted by LL-RVS. (3) The frequency and amplitude of the neural activity recorded from the ARGP were markedly inhibited by LL-RVS. LL-RVS suppressed AF inducibility and the chronotropic responses to parasympathetic and sympathetic stimulation. Inhibition of neural activity in the GP may be a mechanism underlying these results.

Use of a Gain-Of-Function BK Channel to Suppress Neural Excitability

BK channels have a uniquely large single channel conductance and are activated in physiological settings by coincident membrane depolarization and rise in intracellular Ca2+ (Ca2+i). Increasing K+ conductances, in many instances, reduces neuronal activity. In this study we used a ‘gain-of-function’ BK channel as a tool to suppress neural excitability. We created a BK channel construct with an Arginine (R) to Glutamine (Q) point mutation in the S4 voltage sensor. Previous studies in Xenopus oocytes with symmetrical K+ solutions showed that R207Q results in a significant negative shift in the channel's voltage-dependence of activation through reduced coupling between Ca2+ binding and channel opening (Diaz et al, 1998). To address how this mutation would affect excitability in mammalian cells under physiological conditions, we recorded from inside-out patches excised from HEK293T cells at various [Ca2+]i. Wild-type (WT) BK and R207Q cDNAs were expressed separately and together to form homo- and putative heterotetramers. Currents from R207Q alone and WT/R207Q co-expression both display strong gain-of-function properties in HEK cells under physiological conditions. The V0.5s for WT, WT/R207Q and R207Q currents with nominal [Ca2+]i were 113.5 ±3.5, 67.0 ±5.2 and 24.3 ±3.3 mV, respectively. In addition, currents recorded from R207Q- and WT/R207Q-expressing HEK cells with nominal [Ca2+]i activated faster than WT currents with 5 µM [Ca2+]i, at +80 mV (Tau activation=1.6 ±0.2, 2.1 ±0.2 and 5.8 ±2.6 ms, respectively). Overall, WT/R207Q currents in the absence of Ca2+i were similar to WT currents with 50 µM Ca2+i. When an R207Q transgene was expressed in mouse hypothalamic neurons with endogenous BK channels present, action potential frequency was suppressed (WT: 33.3 ±3.2 versus R207Q: 65.5 ±7.3 Hz). This work demonstrates that cells expressing R207Q channels have hyperactive BK currents, resulting in suppression of neural activity under physiological conditions.

Dual Mechanism of Neuronal Ensemble Inhibition in Primary Auditory Cortex

Inhibition plays an essential role in shaping and refining the brain's representation of sensory stimulus attributes. In primary auditory cortex (A1), so-called "sideband" inhibition helps to sharpen the tuning of local neuronal responses. Several distinct types of anatomical circuitry could underlie sideband inhibition, including direct thalamocortical (TC) afferents, as well as indirect intracortical mechanisms. The goal of the present study was to characterize sideband inhibition in A1 and to determine its mechanism by analyzing laminar profiles of neuronal ensemble activity. Our results indicate that both lemniscal and nonlemniscal TC afferents play a role in inhibitory responses via feedforward inhibition and oscillatory phase reset, respectively. We propose that the dynamic modulation of excitability in A1 due to the phase reset of ongoing oscillations may alter the tuning of local neuronal ensembles and can be regarded as a flexible overlay on the more obligatory system of lemniscal feedforward type responses.

Failure of repetition suppression and memory encoding in aging and Alzheimer’s disease

The suppression of neural activity in the medial temporal lobe (MTL) has been suggested as a marker of successful recognition of familiarity in healthy subjects, but to be impaired in patients with Alzheimer's disease (AD). In this study, we investigated whether the ability to suppress MTL activity during repeated exposure to face-name pairs was related to the ability to successfully encode novel associations in 90 individuals ranging from healthy young and older subjects to mildly impaired elderly and AD patients. Activity in the anterior MTL during Repeated stimuli was inversely related to performance in post-scan associative recognition for the Novel face-name pairs. In a subset (n=60) of subjects undergoing more detailed neuropsychological testing, greater MTL Repeated activity was correlated with worse word-list delayed recall performance. Failure of response suppression to familiar information may be a sensitive marker of MTL dysfunction and memory impairment in aging and prodromal AD.

Task-dependent differences in corticobulbar excitability of the submental motor projections: Implications for neural control of swallowing

It has been suggested that the primary motor cortex plays a substantial role in the neural circuitry that controls swallowing. Although its role in the voluntary oral phase of swallowing is undisputed, its precise role in motor control of the more reflexive, pharyngeal phase of swallowing is unclear. The contribution of the primary motor cortex to the pharyngeal phase of swallowing was examined using transcranial magnetic stimulation (TMS) to evoke motor evoked potentials (MEPs) in the anterior hyomandibular muscle group during either volitional submental muscle contraction or contraction during the pharyngeal phase of both volitionally, and reflexively, initiated swallowing. For each subject, in all three conditions, TMS was triggered when submental surface EMG (sEMG) reached 75% of the mean maximal submental sEMG amplitude measured during 10 volitional swallows. MEPs recorded during volitional submental muscle contraction were elicited in 22 of the 35 healthy subjects examined (63%). Only 16 of these 22 subjects (45.7%) also displayed MEPs recorded during volitional swallowing, but their MEP amplitudes were larger when triggered by submental muscle contraction than when triggered by volitional swallowing. Additionally, only 7 subjects (of 19 tested) showed MEPs triggered by submental muscle contraction during a reflexively triggered pharyngeal swallow. These differences indicate differing levels of net M1 excitability during execution of the investigated tasks, possibly brought about by task-dependent changes in the balance of excitatory and inhibitory neural activity.

Analysis of GABAergic and Non-GABAergic Neuron Activity in the Optic Lobes of the Forager and Re-Orienting Worker Honeybee (Apis mellifera L.)

BackgroundEuropean honeybee (Apis mellifera L.) foragers have a highly developed visual system that is used for navigation. To clarify the neural basis underlying the highly sophisticated visual ability of foragers, we investigated the neural activity pattern of the optic lobes (OLs) in pollen-foragers and re-orienting bees, using the immediate early gene kakusei as a neural activity marker.Methodology/Principal FindingsWe performed double-in situ hybridization of kakusei and Amgad, the honeybee homolog of the GABA synthesizing enzyme GAD, to assess inhibitory neural activity. kakusei-related activity in GABAergic and non-GABAergic neurons was strongly upregulated in the OLs of the foragers and re-orienting bees, suggesting that both types of neurons are involved in visual information processing. GABAergic neuron activity was significantly higher than non-GABAergic neuron activity in a part of the OLs of only the forager, suggesting that unique information processing occurs in the OLs of foragers. In contrast, GABAergic neuron activity in the antennal lobe was significantly lower than that of GABAergic neurons in the OLs in the forager and re-orienting bees, suggesting that kakusei-related visual activity is dominant in the brains of these bees.Conclusions/SignificanceThe present study provides the first evidence that GABAergic neurons are highly active in the OL neurons of free-moving honeybees and essential clue to reveal neural basis of the sophisticated visual ability that is equipped in the small and simple brain.

Optogenetically induced suppression of neural activity in the macaque motor cortex

Optogenetically induced suppression of neural activity in the macaque motor cortex

Bottom-Up Driven Involuntary Auditory Evoked Field Change: Constant Sound Sequencing Amplifies But Does Not Sharpen Neural Activity

The capability of involuntarily tracking certain sound signals during the simultaneous presence of noise is essential in human daily life. Previous studies have demonstrated that top-down auditory focused attention can enhance excitatory and inhibitory neural activity, resulting in sharpening of frequency tuning of auditory neurons. In the present study, we investigated bottom-up driven involuntary neural processing of sound signals in noisy environments by means of magnetoencephalography. We contrasted two sound signal sequencing conditions: "constant sequencing" versus "random sequencing." Based on a pool of 16 different frequencies, either identical (constant sequencing) or pseudorandomly chosen (random sequencing) test frequencies were presented blockwise together with band-eliminated noises to nonattending subjects. The results demonstrated that the auditory evoked fields elicited in the constant sequencing condition were significantly enhanced compared with the random sequencing condition. However, the enhancement was not significantly different between different band-eliminated noise conditions. Thus the present study confirms that by constant sound signal sequencing under nonattentive listening the neural activity in human auditory cortex can be enhanced, but not sharpened. Our results indicate that bottom-up driven involuntary neural processing may mainly amplify excitatory neural networks, but may not effectively enhance inhibitory neural circuits.

Predictive knowledge of stimulus relevance does not influence top-down suppression of irrelevant information in older adults

Our ability to focus attention on task-relevant stimuli and ignore irrelevant distractions is reflected by differential enhancement and suppression of neural activity in sensory cortices. Previous research has shown that older adults exhibit a deficit in suppressing task-irrelevant information, the magnitude of which is associated with a decline in working memory performance. However, it remains unclear if a failure to suppress is a reflection of an inability of older adults to rapidly assess the relevance of information upon stimulus presentation when they are not aware of the relevance beforehand. To address this, we recorded the electroencephalogram (EEG) in healthy older participants (aged 60—80 years) while they performed two different versions of a selective face/scene working memory task, both with and without prior knowledge as to when relevant and irrelevant stimuli would appear. Each trial contained two faces and two scenes presented sequentially followed by a 9 sec delay and a probe stimulus. Participants were given the following instructions: remember faces (ignore scenes), remember scenes (ignore faces), remember the xth and yth stimuli (where x and y could be 1st, 2nd, 3rd or 4th), or passively view all stimuli. Working memory performance remained consistent regardless of task instructions. Enhanced neural activity was observed at posterior electrodes to attended stimuli, while neural responses that reflected the suppression of irrelevant stimuli was absent for both tasks. The lack of significant suppression at early stages of visual processing was revealed by P1 amplitude and N1 latency modulation indices. These results reveal that prior knowledge of stimulus relevance does not modify early neural processing during stimulus encoding and does not improve working memory performance in older adults. These results suggest that the inability to suppress irrelevant information early in the visual processing stream by older adults is related to mechanisms specific to top-down suppression.

Inhibition of neural activity depletes orexin from rat hypothalamic slice culture

Orexins (hypocretins) are neuropeptides produced by a small population of hypothalamic neurons whose dysregulation may lead to narcolepsy, a neurological disorder characterized by disorganization of sleep and wakefulness. Excessive stimulation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors causes preferential loss of orexin neurons in the hypothalamus, whereas an adequate level of neuronal excitatory activities is generally known to be important for the maintenance of central neurons. By examining the effect of manipulation of neural activity, we found that 24-72 hr application of tetrodotoxin (TTX) caused a substantial decrease in the number of orexin-immunoreactive neurons, but not of melanin-concentrating hormone-immunoreactive neurons, in hypothalamic slice culture. Similar results were obtained when neural activity was arrested by added extracellular Mg(2+). Reduction of orexin expression by TTX and Mg(2+) was also observed at mRNA level. The decrease of orexin-immunoreactive neurons was attributable to depletion of orexin, because it was reversible after washout of TTX or elevated extracellular Mg(2+) and was not associated with induction of cell death. Blockers of voltage-dependent Ca(2+) channels as well as of NMDA receptors also induced a significant and selective decrease of orexin-immunoreactive neurons. Moreover, TTX-induced decrease of orexin immunoreactivity was largely abrogated by concurrent application of a moderate concentration of NMDA. These results suggest that Ca(2+) entry associated with nontoxic levels of spontaneous activity of glutamatergic inputs plays an important role in the maintenance of orexin neurons in a tissue culture model.

Neural Suppression of Irrelevant Information Underlies Optimal Working Memory Performance

Our ability to focus attention on task-relevant information and ignore distractions is reflected by differential enhancement and suppression of neural activity in sensory cortex (i.e., top-down modulation). Such selective, goal-directed modulation of activity may be intimately related to memory, such that the focus of attention biases the likelihood of successfully maintaining relevant information by limiting interference from irrelevant stimuli. Despite recent studies elucidating the mechanistic overlap between attention and memory, the relationship between top-down modulation of visual processing during working memory (WM) encoding, and subsequent recognition performance has not yet been established. Here, we provide neurophysiological evidence in healthy, young adults that top-down modulation of early visual processing (< 200 ms from stimulus onset) is intimately related to subsequent WM performance, such that the likelihood of successfully remembering relevant information is associated with limiting interference from irrelevant stimuli. The consequences of a failure to ignore distractors on recognition performance was replicated for two types of feature-based memory, motion direction and color. Moreover, attention to irrelevant stimuli was reflected neurally during the WM maintenance period as an increased memory load. These results suggest that neural enhancement of relevant information is not the primary determinant of high-level performance, but rather optimal WM performance is dependent on effectively filtering irrelevant information through neural suppression to prevent overloading a limited memory capacity.

Heme-oxygenase-2 immunolabelling in pig jejunum

Heme-oxygenase-2 generates carbon monoxide in the enteric nervous system and in interstitial cells of Cajal in the canine, mouse and human jejunum. Carbon monoxide is considered a non-adrenergic and non-cholinergic inhibitory neurotransmitter and it establishes and maintains the resting membrane potential in the stomach and small intestine. The aim of this study was to determine the distribution of heme-oxygenase-2 in the enteric nervous system of the pig jejunum. Heme-oxygenase-2 immunoreactivity was found in neurons of myenteric ganglia and in nerve fibers in the circular and longitudinal muscle layers. These results suggest that carbon monoxide is produced in the enteric nervous system of the pig jejunum and might mediate inhibitory neural activity in myenteric ganglia and inhibitory neural input to smooth muscle cells in the circular and longitudinal muscle layers.

Frequency-specific modulation of population-level frequency tuning in human auditory cortex

BackgroundUnder natural circumstances, attention plays an important role in extracting relevant auditory signals from simultaneously present, irrelevant noises. Excitatory and inhibitory neural activity, enhanced by attentional processes, seems to sharpen frequency tuning, contributing to improved auditory performance especially in noisy environments. In the present study, we investigated auditory magnetic fields in humans that were evoked by pure tones embedded in band-eliminated noises during two different stimulus sequencing conditions (constant vs. random) under auditory focused attention by means of magnetoencephalography (MEG).ResultsIn total, we used identical auditory stimuli between conditions, but presented them in a different order, thereby manipulating the neural processing and the auditory performance of the listeners. Constant stimulus sequencing blocks were characterized by the simultaneous presentation of pure tones of identical frequency with band-eliminated noises, whereas random sequencing blocks were characterized by the simultaneous presentation of pure tones of random frequencies and band-eliminated noises. We demonstrated that auditory evoked neural responses were larger in the constant sequencing compared to the random sequencing condition, particularly when the simultaneously presented noises contained narrow stop-bands.ConclusionThe present study confirmed that population-level frequency tuning in human auditory cortex can be sharpened in a frequency-specific manner. This frequency-specific sharpening may contribute to improved auditory performance during detection and processing of relevant sound inputs characterized by specific frequency distributions in noisy environments.

An anti-immobility effect of exogenous corticosterone in mice

Although traditionally considered to be etiological factors in depression, corticosteroids have been shown to exert an acute antidepressant action under some conditions. To investigate the mechanism of this effect, the present experiment sought to develop an animal model of it in mice using the repeated forced swim procedure. Corticosterone or desmethylimipramine was administered in the drinking water before, during or after repeated daily forced swims or a tail suspension test. Glucocorticoid and mineralocorticoid receptor involvement were assessed by coadministration of RU486 or spironolactone. Plasma corticosterone and fos expression in the paraventricular nucleus of the hypothalamus and piriform cortex were also measured in the treated animals. Corticosterone, given either before/during or after repeated swim, was found to produce a rapid reduction of immobility that was greater than that produced by desmethylimipramine given by the same route and dose and for the same duration. There was a nonsignificant tendency toward this effect in the tail suspension test. RU486 failed to block the effect but results with spironolactone were ambiguous. Plasma corticosterone was elevated in an inverted U-shaped fashion by the hormone treatment. Fos expression in response to the last swim was blunted in the paraventricular hypothalamus but enhanced in the piriform cortex. It is concluded that short-term treatment with corticosterone has a marked antidepressant effect in the mouse repeated forced swim test and merits further consideration as a short-term therapeutic agent in low doses. The hormone may act by suppression of neural activity in central stress circuits leading to a disinhibition of regions involved in active behavioral coping.

Asymmetric lateral inhibitory neural activity in the auditory system: a magnetoencephalographic study

BackgroundDecrements of auditory evoked responses elicited by repeatedly presented sounds with similar frequencies have been well investigated by means of electroencephalography and magnetoencephalography (MEG). However the possible inhibitory interactions between different neuronal populations remains poorly understood. In the present study, we investigated the effect of proceeding notch-filtered noises (NFNs) with different frequency spectra on a following test tone using MEG.ResultsThree-second exposure to the NFNs resulted in significantly different N1m responses to a 1000 Hz test tone presented 500 ms after the offset of the NFNs. The NFN with a lower spectral edge closest to the test tone mostly decreased the N1m amplitude.ConclusionThe decrement of the N1m component after exposure to the NFNs could be explained partly in terms of lateral inhibition. The results demonstrated that the amplitude of the N1m was more effectively influenced by inhibitory lateral connections originating from neurons corresponding to lower rather than higher frequencies. We interpret this effect of asymmetric lateral inhibition in the auditory system as an important contribution to reduce the asymmetric neural activity profiles originating from the cochlea.

Suppression of neural activity and hemodynamic responses during hypercapnic challenges in rats

Suppression of neural activity and hemodynamic responses during hypercapnic challenges in rats

Turing instability and pattern formation in a two-population neuronal network model

A two-population firing-rate model describing the dynamics of excitatory and inhibitory neural activity in one spatial dimension is investigated with respect to formation of patterns, in particular stationary periodic patterns and spatiotemporal oscillations. Conditions for existence of spatially homogeneous equilibrium states are first determined, and the stability properties of these equilibria are investigated. It is shown that the nonlocal synaptic interactions may promote a finite bandwidth instability in a way analogous to diffusion effects in the classical Turing instability for reaction–diffusion equations and modulational instability in the theory of nonlinear waves in nonlocal defocusing Kerr media. Our analysis relies on the wave-number dependent invariants of the 2×2-matrix representing the spatially Fourier-transformed linearized evolution equations. The generic picture which emerges is an instability consisting of a finite set of well-separated unstable bands in wave-number space (gain bands). The case with symmetrical, exponentially decaying connectivity functions is investigated in detail, allowing for a more comprehensive analysis of the gain-band structure, and, in particular, conditions for the excitation of a single gain band through a Turing–Hopf bifurcation with the relative inhibition time constant as control parameter. Two typical situations emerge depending on the thresholds and inclinations of the sigmoidal firing-rate functions: (i) A single gain-band is excited through a Turing–Hopf bifurcation, and the resulting state is a spatiotemporally oscillating pattern, or (ii) the instability develops into a stationary periodic pattern, i.e. a set of equidistant bumps. The dependence of instability-type on the inclinations of the firing-rate function and the time constant are comprehensively investigated, demonstrating, for example, that only stationary patterns can be generated for sufficiently small inhibitory time constants. The nonlinear development of the gain-band instabilities is further elucidated by direct numerical simulations.

Ischemia-induced disturbance of neuronal network function in the rat spinal cord analyzed by voltage-imaging

Using a voltage-imaging technique, we analyzed the acute effect of ischemia, hypoxia and hypoglycemia on the neuronal network function of the rat spinal cord. Ischemic, hypoxic, or hypoglycemic stress was loaded to spinal cord slices with an oxygen- and glucose-free, oxygen-free, or glucose-free mock cerebrospinal fluid, respectively. Depolarizing signals in the dorsal horn, induced by dorsal root stimulation, consisted of fast (pre-synaptic) and slow (post-synaptic) components. The slow component was attenuated much more than the fast component under an ischemic condition ( P<0.0002). Post-synaptic neuronal activities in lamina III–IV were suppressed earlier than those in lamina I–II. The nerve fiber was relatively resistant to ischemia. As long as the fast component was preserved in the dorsal horn, the suppression of the fast and slow components was reversible. There was a significant difference ( P<0.05) in the recovered slow component sizes between the group in which the fast component was suppressed by more than 20% by ischemia and the group in which the suppression was less than 20%. Further prolonged stress irreversibly eliminated most of the slow component, and attenuated the fast component (to 59±8%) accompanied by cellular damage in histology. Suppression of neural activity by hypoxic or hypoglycemic stress was less prominent than that by ischemia. Prolonged ischemic stress suddenly and irreversibly eliminated depolarizing signals in the ventral horn accompanied by morphological damage of motoneurons. Immunohistochemical staining was negative for apoptosis. We have, for the first time, analyzed the processes of spinal cord disturbance induced by ischemia, hypoxia and hypoglycemia at the neuronal network level by directly observing the regional neuronal network activities within the spinal cord. We conclude that synaptic transmission in the dorsal horn, especially in deep regions, is vulnerable and first affected by these stresses. Severe ischemic stress induces irreversible dysfunction of neurons accompanied by eventual cell death in both dorsal and ventral horns.