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At least 145 records · Page 8Linked to original sources

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.

Animals↗

[Three dimensional stereotactic functional neurosurgical planning].

In order to arrive the small area in the deep brain with minimum invasion, stereotactic technique is useful. Subthalamic nucleus stimulation with this technique has been common for Parkinson disease. Recently some papers reported the cognitive performance change after implantation and there were some discussion about the electrode trajectory. Though we didn't have the answer until now, three-dimensional target included the trajectory seems to be important. Another way, stereotactic technique was used the epilepsy evaluation. The point of this procedure was based on the clinical aspect, the well-known neural network and the anatomical understanding for each patient. Three-dimensional anatomical target provides us the best treatment for stereotactic neurosurgery.

Electric Stimulation Therapy↗

Basal ganglia neural responses during behaviorally effective deep brain stimulation of the subthalamic nucleus in rats performing a treadmill locomotion test.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for Parkinson's disease (PD). In spite of proven therapeutic success, the mechanism underlying the benefits of DBS has not been resolved. A multiple-channel single-unit recording technique was used in the present study to investigate basal ganglia (BG) neural responses during behaviorally effective DBS of the STN in a rat model of PD. Rats underwent unilateral dopamine (DA) depletion by injection of 6-hydroxyDA (6-OHDA) into one side of the medial forebrain bundle and subsequently developed a partial akinesia, which was assessed during the treadmill locomotion task. High frequency stimulation (HFS) of the STN restored normal treadmill locomotion behavior. Simultaneous recording of single unit activity in the striatum (STR), globus pallidus (GP), substantia nigra pars reticulata (SNr), and STN revealed a variety of neural responses during behaviorally effective HFS of the STN. Predominant inhibitory responses appeared in the STN stimulation site. Nearly equal numbers of excitatory and inhibitory responses were found in the GP and SNr, whereas more rebound excitatory responses were found in the STR. Mean firing rate did not change significantly in the STR, GP, and SNr, but significantly decreased in both sides of STN during DBS. A decrease in firing rate in the contralateral side of STN provides neural substrate for the clinical observation that unilateral DBS produces bilateral benefits in patients with PD. In addition to the firing rate changes, a decrease in burst firing was observed in the GP and STN. The present study indicates that DBS induces complex modulations of the BG circuit and further suggests that BG network reorganization, rather than a simple excitation or inhibition, may underlie the therapeutic effects of DBS in patients with PD.

Adrenergic Agents↗

GBFN: A gated bimodal fusion network leveraging foundation model embeddings for cancer drug sensitivity prediction.

Despite recent progress in deep learning for cancer drug sensitivity prediction, many existing models still rely on task-specific representation learning or relatively simple multimodal fusion, which may limit their ability to capture complex drug-cell interactions. To address this issue, we developed GBFN, a gated bimodal fusion network for continuous IC50 prediction that integrates pretrained drug and cell-line representations. Specifically, drug embeddings were obtained from SMI-TED, whereas cell-line embeddings were derived from transcriptomic profiles using BulkFormer. These two modalities were then combined through a dimension-wise gated fusion module and used to predict IC50 values in matched drug-cell line pairs. On the CCLE-based benchmark, GBFN outperformed representative neural baselines, including GraphDRP, TGSA, and TransEDRP, and achieved the best overall performance, with an R&#xb2; of 0.8714 and an RMSE of 0.8938. Moreover, ablation analysis showed that the model using drug features and cell-line expression data with gated fusion performed better than the corresponding model using direct concatenation, indicating that the improvement was associated with the fusion strategy rather than with the input modalities alone. In addition, cell-line expression data were more informative than mutation data in the present setting, and adding mutation data to the model using drug features and expression data did not further improve performance. Across major cancer types, GBFN maintained generally high cell-line-level predictive performance, and perturbation-based attribution identified biologically relevant transcriptomic programs in selected drug-cell line settings. Together, these findings support GBFN as a compact and effective framework for continuous drug response prediction.

Humans↗

Delayed feedback control of collective synchrony: an approach to suppression of pathological brain rhythms.

We suggest a method for suppression of synchrony in a globally coupled oscillator network, based on the time-delayed feedback via the mean field. Having in mind possible applications for suppression of pathological rhythms in neural ensembles, we present numerical results for different models of coupled bursting neurons. A theory is developed based on the consideration of the synchronization transition as a Hopf bifurcation.

Action Potentials↗

Peripheral sympathetic innervation of the deep pineal gland of the golden hamster.

Both the superficial and deep pineal components of the intact hamster contain a rich network of green to yellow-green fluorescent nerve fibres. After either superior cervical ganglionectomy or after transection of the nervi conarii the majority of the fluorescing fibres disappeared from both the superficial and deep pineal masses. Although the deep pineal remained intact after surgical removal of the superficial pineal, it was devoid of any green or yellow-green fluorescent fibres.

Animals↗

Low-frequency subthalamic oscillations increase after deep brain stimulation in Parkinson's disease.

This work is the second of a series of papers in which we investigated the neurophysiological basis of deep brain stimulation (DBS) clinical efficacy using post-operative local field potential (LFP) recordings from DBS electrodes implanted in the subthalamic nucleus (STN) in patients with Parkinson's disease. We found that low-frequency (1-1.5Hz) oscillations in LFP recordings from the STN of patients with Parkinson's disease dramatically increase after DBS of the STN itself (log power change=0.93+/-0.62; Wilcoxon: p=0.0002, n=13), slowly decaying to baseline levels after turning DBS off. The DBS-induced increase of low-frequency LFP oscillations is highly reproducible and appears only after the delivery of DBS for a time long enough to induce clinical improvement. This increase of low-frequency LFP oscillations could reflect stimulation-induced modulation of network activity or could represent changes of the electrochemical properties at the brain-electrode interface.

Action Potentials↗

Entorhinal cortex projection cells to the hippocampal formation in vitro.

Retrogradely labeled cells in superficial and deep layers of the entorhinal cortex (EC) were analyzed following application of the fluorescent tracer rhodamine-dextran-amine in different sites of the hippocampal formation in a slice preparation. The results demonstrate a strong projection from layer IV/V to the dentate gyrus, that is in slices significantly stronger than that from layer II. In deep layers a large number of multipolar cells were found which were only labeled by dye application to the subiculum. Patch-clamp recordings from these cells revealed intrinsic low threshold membrane potential oscillations, suggesting their possible contribution to oscillatory network activity of the EC and subiculum.

Animals↗

Novel interneuronal network in the mouse posterior piriform cortex.

The neural circuits of the piriform cortex mediate field potential oscillations and complex functions related to integrating odor cues with behavior, affective states, and multisensory processing. Previous anatomical studies have established major neural pathways linking the piriform cortex to other cortical and subcortical regions and major glutamatergic and GABAergic neuronal subtypes within the piriform circuits. However, the quantitative properties of diverse piriform interneurons are unknown. Using quantitative neural anatomical analysis and electrophysiological recording applied to a GAD65-EGFP transgenic mouse expressing GFP (green fluorescent protein) under the control of the GAD65 promoter, here we report a novel inhibitory network that is composed of neurons positive for GAD65-EGFP in the posterior piriform cortex (PPC). These interneurons had stereotyped dendritic and axonal properties that were distinct from basket cells or interneurons expressing various calcium-binding proteins (parvalbumin, calbindin, and calretinin) within the PPC. The GAD65-GFP neurons are GABAergic and outnumbered any other interneurons (expressing parvalbumin, calbindin, and calretinin) we studied. The firing pattern of these interneurons was highly homogenous and is similar to the regular-spiking nonpyramidal (RSNP) interneurons reported in primary sensory and other neocortical regions. Robust dye coupling among these interneurons and expression of connexin 36 suggested that they form electrically coupled networks. The predominant targets of descending axons of these interneurons were the dendrites of Layer III principal cells. Additionally, synapses were found on dendrites and somata of deep Layer II principal neurons and Layer III basket cells. A similar interneuronal subtype was also found in GAD65-EGFP-negative mouse. The extensive dendritic bifurcation at superficial lamina IA among horizontal afferent fibers and unique axonal targeting pattern suggests that these interneurons may play a role in direct feedforward inhibitory and disinhibitory olfactory processing. We conclude that the GAD65-GFP neurons may play distinct roles in regulating information flow and olfactory-related oscillation within the PPC in vivo.

Animals↗

Data-driven approaches in green microbiology: strategies for plant growth-promoting bacteria.

Plant growth-promoting bacteria (PGPB) are gaining attention as scalable biological solutions to enhance crop productivity and resilience. However, accurately identifying and characterizing PGPB remains challenging, particularly under variable environmental conditions where microbial functions are context-dependent and shaped by complex plant-microbe interactions. Advances in high-throughput sequencing have shifted the field from culture-dependent approaches to genome-informed strategies, enabling large-scale taxonomic and functional profiling. Although trait-based databases support the prediction of plant-beneficial genes, they capture only a fraction of the underlying biological complexity and often require labor-intensive analyses. Machine learning (ML) and deep learning (DL) have emerged as powerful tools to integrate genomic, physiological, and ecological data, enabling the prioritization of candidate strains with plant growth-promoting potential. To evaluate advances in the field, we conducted a systematic review of studies integrating ML and DL with PGPB characterization, assessing algorithm selection, performance, and target plant systems. Across 248 observations, only 6.0% of studies directly addressed PGPB screening, whereas the majority (77.4%) focused on plant disease detection, revealing a substantial gap in the application of AI to beneficial microorganisms for plant growth. Convolutional neural networks (CNNs) were the most frequently applied algorithms, largely driven by image-based phenotyping tasks. Overall, the field is constrained by limited datasets, high computational demands, and challenges in modeling multispecies and host-associated interactions. We highlight the need for integrative and interpretable ML and DL frameworks that bridge genomic data and functional validation. Such approaches represent a promising path toward scalable, data-driven discovery and deployment of bioinoculants in sustainable agriculture.

Agriculture↗

Entorhinal cortex of the monkey: VII. intrinsic connections.

The organization of intrinsic connections within the entorhinal cortex was investigated in Macaca fascicularis monkeys. Anterograde tracers ((3)H-amino acids, Phaseolus vulgaris-leucoagglutinin, biotinylated dextran amine, or Fluoro-Ruby) were injected into the deep or superficial layers of the entorhinal cortex in 24 animals. These injections labeled extensive intrinsic projections that terminated throughout all layers of the entorhinal cortex. Labeling was typically continuous i.e., there was no evidence of a patchy or columnar organization. Each injection produced a rostrocaudally oriented band of labeled fibers and terminals that extended for one-third to one-half of the length of the entorhinal cortex. The more extensive distributions of labeled fibers were more typical of caudally placed injection sites. Taken together, the projections identified at least two mediolaterally differentiated bands: a lateral band that encompasses fields Elr, Elc, and the most lateral aspect of fields Ec and Ecl and a wider, medially situated band that encompasses much of fields Er, Ei, Ec, and Ecl. We obtained some evidence that field Eo constitutes a third, very medially placed band. The rostrocaudal organization of labeled fibers and the extent of labeling within the deep and superficial layers were unrelated to the laminar position of the injection. These data suggest that intrinsic associatonal connections in the monkey entorhinal cortex are organized into separate associational networks. Our findings are discussed with reference to the role of interlaminar connections in mediating physiological interactions between the neocortex and the hippocampus.

Animals↗

A decision support system to detect morphologic changes of chromatin arrangement in normal-appearing cells.

Several studies have described malignancy-associated changes (MACs) of chromatin arrangement in the nuclei of apparently normal cells adjacent to and distant from an invasive cancer area. MAC assessment is a hard task, since it requires a deep knowledge of morphologic features of chromatin arrangement. The aim of this work is to verify the reproducibility of the subjective evaluation of the expert on the basis of a decision support system (DSS) that automatically and objectively reproduces MAC diagnosis. A set of 61 patients with suspected clinical diagnosis for lung cancer has been taken into account. The scientist who first described MAC defined each patient as MAC positive or negative on the basis of the MAC diagnosis performed on all cells of the related cytologic sample. A DSS based on an artificial neural network has been set up to learn the relation between 14 morphometric and texture parameters, computed on each nucleus by image processing techniques, with the MAC diagnosis of the expert on each cell. The results show that an objective automatic assessment on MAC by the DSS can effectively support the MAC diagnosis. The method adopted in this approach may be also appropriate for other problems, where an automatic classification of visually inspected patterns of biological micro- and submicrostructure is needed.

Algorithms↗

Uncovering the mechanisms of deep brain stimulation for Parkinson's disease through functional imaging, neural recording, and neural modeling.

High-frequency deep brain stimulation (DBS) of the thalamus or basal ganglia represents an effective clinical technique for the treatment of several medically refractory movement disorders, including Parkinson's disease. However, understanding of the mechanisms of action of DBS remains elusive. The goal of this review is to address our understanding of the effects of high-frequency stimulation within the central nervous system based on results from functional imaging, neural recording, and neural modeling experiments. Using these results, we address the main hypotheses on the mechanisms of action of DBS and conclude that stimulation-induced desynchronization of network oscillations represents the hypothesis that best explains the presently available data.

Basal Ganglia↗

Histochemical localization of nitric oxide-synthesizing neurons and vascular sites in the guinea-pig intestine.

Laminar preparations of fixed segments of the guinea-pig intestine were examined for nitric oxide synthase activity using reduced nicotinamide adenine dinucleotide phosphate and nitroblue tetrazolium salt as substrates. Under conditions specific for detecting nitric oxide synthase-related diaphorase activity, a subpopulation of neural elements in the myenteric plexus, deep muscular plexus and submucosa were intensely stained. Intensely stained nerve fibres were distributed throughout the meshworks of the myenteric plexus and its innervation of the circular muscle, and in the submucosa within Henle's plexus. Intensely stained nerve cells and their processes were evident in most myenteric ganglia but were rare in ganglia of Henle's plexus. Stained ganglion cells comprised types I, II and VI of the morphologically defined enteric nerve cells. Stained neural elements were increasingly prevalent within successively more caudal segments of the intestine. In addition to neuronal staining, arterioles of the submucosal vascular network displayed distinct, punctate patches of staining distributed over their surface. Perivascular nerve fibre staining was absent. These results show nitric oxide synthase activity to be present within neurons and fibres of the major enteric nerve layers and within submucosal blood vessels throughout the guinea-pig small and large intestine.

Amino Acid Oxidoreductases↗

Substance P-, calcitonin gene-related peptide- and C-flanking peptide of neuropeptide Y-immunoreactive fibres are present in normal synovium but depleted in patients with rheumatoid arthritis.

By means of antisera to cytoplasmic components of nerve fibres and neuropeptides which are known to be present in sensory or sympathetic nerves we have examined the distribution of both total and different types of nerve fibres in normal and inflamed human synovial tissue. Samples of synovia were obtained at surgery from five normal and five rheumatoid patients (age range 10-77 years). In order to map the overall neural innervation of the synovium, antiserum to the general neuronal marker protein gene product 9.5 was employed. Substance P and calcitonin gene-related peptide antisera were employed to identify sensory fibres and antisera to the C-flanking peptide of neuropeptide Y to distinguish sympathetic nerves. In normal synovium protein gene product 9.5-immunoreactive fibres were numerous, in particular, the vasculature was densely innervated. Free protein gene product 9.5-immunoreactive fibres were less numerous but were present in all synovia examined, and in many cases these extended to the intimal layer. Neuropeptide immunostaining was predominantly found in perivascular networks. Fibres immunoreactive for the C-flanking peptide of neuropeptide Y were exclusively located around blood vessels whereas free fibres were immunoreactive for substance P or calcitonin gene-related peptide. As with free protein gene product 9.5-immunoreactive fibres, fibres expressing substance P or calcitonin gene-related peptide immunoreactivity were often seen in the intimal cell layer. In rheumatoid arthritis a similar innervation to that seen in normal synovium was apparent in the deep tissue but fibres immunoreactive for protein gene product 9.5, the C-flanking peptide of neuropeptide Y, substance P or calcitonin gene-related peptide were not visible in the more superficial tissues or the intimal cell layer. In addition, immunostaining of neuropeptides in the deep tissue was weaker in the diseased tissues than in normal controls. The data unequivocally demonstrate that synovial tissues are richly innervated and confirm the presence of both sensory and sympathetic nerves. The absence of nerves which innervate the superficial synovium in rheumatoid arthritis might suggest that there is increased release of substance P, calcitonin gene-related peptide and the C-flanking peptide of neuropeptide Y, reducing the stores in the nerves to levels below that detectable by immunocytochemistry. However, since protein gene product 9.5-immunoreactive nerves were not seen in the inflamed tissue it is probable that synovial growth outflanks neural growth and consequently as the disease progresses neural structures become restricted to deeper tissues.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Long-term anti-kindling effects of desynchronizing brain stimulation: a theoretical study.

In a modeling study we show that desynchronization stimulation may have powerful anti-kindling effects. For this, we incorporate spike-timing-dependent plasticity into a generic network of coupled phase oscillators, which serves as a model network of synaptically interacting neurons. Two states may coexist under spontaneous conditions: a state of uncorrelated firing and a state of pathological synchrony. Appropriate stimulation protocols make the network learn or unlearn the pathological synaptic interactions, respectively. Low-frequency periodic pulse train stimulation causes a kindling. Permanent high-frequency stimulation, used as golden standard for deep brain stimulation in medically refractory movement disorders, basically freezes the synaptic weights. In contrast, desynchronization stimulation, e.g., by means of a multi-site coordinated reset, has powerful long-term anti-kindling effects and enables the network to unlearn pathologically strong synaptic interactions. We propose desynchronization stimulation for the therapy of movement disorders and epilepsies.

Brain↗

Intracortical spread of neuronal activities induced by stimulation of recurrent and thalamic afferent pathways compared with epicortical activation.

In the encéphale isolé cat preparation the cerebral peduncle (CP) and the nucleus ventralis lateralis (VL) of the thalamus were stimulated. Short-latency responses recorded from precruciate cortical neurons consisted of excitatory (EPSP) and inhibitory postsynaptic potentials (IPSP). Laminar distributions of these responses and their latencies wee viewed as the spatiotemporal pattern of spread of excitation and inhibition within the cortex in comparison with those obtained by epicortical stimulation (EPICS). In contrast with activities by EPICS spreading downwards from superficial to deep layers, CP recurrent activities spread upwards from deep to middle or superficial layers, and those by VL afferents spread from middle to both superficial and deep layers bidirectionally. These three intracortical routes shared common cell assemblies in that they received convergent EPSPs or IPSPs to various extents from different inputs. The routes for EPICS and VL inputs were overlapped particularly with abundant supply of convergence in spite of their functional difference. Relevant potentiality of the cerebral network in forming plural patterns was discussed.

Afferent Pathways↗

Medial septal modulation of entorhinal single unit activity in anesthetized and freely moving rats.

Reversible inactivation of the medial septal area results in a spatial memory impairment and selective disruption of hilar/CA3, but not CA1, location-specific discharge. The present study examined the possibility that such septal deafferentation produces effects on hippocampal function by altering physiological properties of the primary input and output structures for hippocampus, the entorhinal cortex and the subiculum, respectively. Single unit activity of hippocampal, entorhinal, and subicular cells was recorded before, during, and after septal injection of lidocaine in anesthetized rats. When compared to hippocampal cells, relatively few subicular and entorhinal cells showed a change in mean firing rate following septal inactivation. Entorhinal unit responses to septal inactivation (via tetracaine injection) were also examined in freely moving rats performing a spatial maze task. About one-third of entorhinal cells showed enhanced or reduced firing rates of 40% or more. Also, the spatial distribution of cells found in the superficial, but not deep, entorhinal layers became less clear following septal inactivation. Together, these data are consistent with the hypothesis that manipulation of the medial septum affects hippocampal function via its septosubicular and septo-entorhinal projections in addition to the more direct septohippocampal pathway. Since entorhinal cortical function was affected by tetracaine injection into the septum, it does not appear that direct entorhinal-CA1 afferents were primarily responsible for the maintenance of CA1 location-specific neural activity in previous septal inactivation experiments. Rather, these data are consistent with the hypothesis that the persistence of CA1 place fields was accomplished by intrahippocampal neural network operations.

Afferent Pathways↗