Nerve Spike Research Articles

Models optimized for real-world tasks reveal the task-dependent necessity of precise temporal coding in hearing.

Neurons encode information in the timing of their spikes in addition to their firing rates. Spike timing is particularly precise in the auditory nerve, where action potentials phase lock to sound with sub-millisecond precision, but its behavioral relevance remains uncertain. We optimized machine learning models to perform real-world hearing tasks with simulated cochlear input, assessing the precision of auditory nerve spike timing needed to reproduce human behavior. Models with high-fidelity phase locking exhibited more human-like sound localization and speech perception than models without, consistent with an essential role in human hearing. However, the temporal precision needed to reproduce human-like behavior varied across tasks, as did the precision that benefited real-world task performance. These effects suggest that perceptual domains incorporate phase locking to different extents depending on the demands of real-world hearing. The results illustrate how optimizing models for realistic tasks can clarify the role of candidate neural codes in perception.

A peripheral subepithelial network for chemotactile processing in the predatory sea slug Pleurobranchaea californica.

Many soft-bodied animals have extensive peripheral nervous systems (PNS) with significant sensory roles. One such, the sea slug Pleurobranchaea californica, uses PNS computations in its chemotactile oral veil (OV) in prey tracking, averaging olfactory stimuli across the OV to target likely source direction, or "stimulus place". This suggests a peripheral subepithelial network (SeN) interconnecting sensory sites to compute the directional average. We pursued anatomy and connectivity of previously described ciliated putative sensory cells on OV papillae. Scanning electron microscopy (SEM) confirmed paddle-shaped cilia in clusters. Anti-tubulin and phalloidin staining showed connections to branching nervelets and muscle fibers for contraction and expansion of papillae. Ciliary cell processes could not be traced into nerves, consistent with sensory transmission to CNS via secondary afferents. Anti-tyrosine hydroxylase-stained ciliated cells in clusters and revealed an at least partially dopaminergic subepithelial network interconnecting clusters near and distant, connections consistent with PNS averaging of multiple stimulated loci. Other, unidentified, SeN neurotransmitters are likely. Confirming chemotactile functions, perfusible suction electrodes recorded ciliary spiking excited by both mechanical and appetitive chemical stimuli. Stimuli induced sensory nerve spiking like that encoding stimulus place. Sensory nerve spikes and cilia cluster spikes were not identifiable as generated by the same neurons. Ciliary clusters likely drive the sensory nerve spikes via SeN, mediating appetitive and stimulus place codes to CNS. These observations may facilitate future analyses of the PNS in odor discrimination and memory, and also suggest such SeNs as potential evolutionary precursors of CNS place-coding circuitry in the segmented, skeletonized protostomes and deuterostomes.

Mesotrode chronic simultaneous mesoscale cortical imaging and subcortical or peripheral nerve spiking activity recording in mice.

Brain function originates from hierarchical spatial-temporal neural dynamics distributed across cortical and subcortical networks. However, techniques available to assess large-scale brain network activity with single-neuron resolution in behaving animals remain limited. Here, we present Mesotrode that integrates chronic wide-field mesoscale cortical imaging and compact multi-site cortical/subcortical cellular electrophysiology in head-fixed mice that undergo self-initiated running or orofacial movements. Specifically, we harnessed the flexibility of chronic multi-site tetrode recordings to monitor single-neuron activity in multiple subcortical structures while simultaneously imaging the mesoscale activity of the entire dorsal cortex. A mesoscale spike-triggered averaging procedure allowed the identification of cortical activity motifs preferentially associated with single-neuron spiking. Using this approach, we were able to characterize chronic single-neuron-related functional connectivity maps for up to 60 days post-implantation. Neurons recorded from distinct subcortical structures display diverse but segregated cortical maps, suggesting that neurons of different origins participate in distinct cortico-subcortical pathways. We extended the capability of Mesotrode by implanting the micro-electrode at the facial motor nerve and found that facial nerve spiking is functionally associated with the PTA, RSP, and M2 network, and optogenetic inhibition of the PTA area significantly reduced the facial movement of the mice. These findings demonstrate that Mesotrode can be used to sample different combinations of cortico-subcortical networks over prolonged periods, generating multimodal and multi-scale network activity from a single implant, offering new insights into the neural mechanisms underlying specific behaviors.

Mesotrode allows chronic simultaneous mesoscale cortical imaging and subcortical or peripheral nerve spiking activity recording in mice

Brain function originates from hierarchical spatial-temporal neural dynamics distributed across cortical and subcortical networks. However, techniques available to assess large-scale brain network activity with single-neuron resolution in behaving animals remain limited. Here, we present Mesotrode that integrates chronic wide-field mesoscale cortical imaging and compact multi-site cortical/subcortical cellular electrophysiology in head-fixed mice that undergo self-initiated running or orofacial movements. Specifically, we harnessed the flexibility of chronic multi-site tetrode recordings to monitor single-neuron activity in multiple subcortical structures while simultaneously imaging the mesoscale activity of the entire dorsal cortex. A mesoscale spike-triggered averaging procedure allowed the identification of cortical activity motifs preferentially associated with single-neuron spiking. Using this approach, we were able to characterize chronic single-neuron-related functional connectivity maps for up to 60 days post-implantation. Neurons recorded from distinct subcortical structures display diverse but segregated cortical maps, suggesting that neurons of different origins participate in distinct cortico-subcortical pathways. We extended the capability of Mesotrode by implanting the micro-electrode at the facial motor nerve and found that facial nerve spiking is functionally associated with the PTA, RSP, and M2 network, and optogenetic inhibition of the PTA area significantly reduced the facial movement of the mice. These findings demonstrate that Mesotrode can be used to sample different combinations of cortico-subcortical networks over prolonged periods, generating multimodal and multi-scale network activity from a single implant, offering new insights into the neural mechanisms underlying specific behaviors.

PO-01-191 CARDIAC NERVE ACTIVITY DURING APNEA IN ATRIAL FIBRILLATION PATIENTS

The cardiac autonomic system (CAS) is involved in the pathogenesis of atrial fibrillation (AF), particularly in AF’s association with sleep apnea. The human CAS response to apnea has not been characterized. The feasibility of CAS nerve recordings in humans has not been established. To record apnea-induced CAS nerve activity in humans before and after AF ablation. Six patients (age 70.8 ± 12.2 years; 66.7% men) undergoing paroxysmal (2/6) or persistent (4/6) AF ablation were enrolled in this study under an IRB-approved protocol. Under ultrasound and fluoroscopy guidance, multipolar catheters (EPR800, Millar, Houston, or EP star, Baylis, Toronto, CA) were placed in the stellate ganglion (SG) bilaterally and in the vein of Marshall (VOM). Nerve signals were recorded using a head stage digitizer via customized adapters and sampled at 30 kHz with a Grapevine recording system (Ripple, Salt Lake City, UT). Under general anesthesia, monitoring of arterial blood pressure, peripheral O2 (pO2) saturation and end-tidal CO2, apnea was induced by stopping ventilation until pO2 reached 90%, after which ventilation resumed. Four apneas were preformed– 2 before and 2 after ablation. Spike2 software (Cambridge Electronic Design, Cambridge, UK) was used to resolve nerve spike morphology, automatically discern spike morphologies, and quantify nerve activity. In all 6 patients, we observed increased VOM local nerve activation triggered by apnea, which were abolished by VOM ethanol infusion and AF ablation. We observed SG activation triggered by apnea in 2 out of 6 patients. In both cases SG activation were exaggerated after VOM ethanol infusion and AF ablation (Figure). In 4/6 SG activations were not recordable. CAS recording in humans undergoing AF ablation is feasible albeit inconsistent in the SG. Apnea produces activations of the CAS. VOM ethanol eliminates local nerve responses to apnea.

MP60-06 INCREASE IN AFFERENT PELVIC NERVE FIRING DURING CONTINUOUS FILLING IN AN ISOLATED PERFUSED PORCINE BLADDER MODEL

You have accessJournal of UrologyCME1 Apr 2023MP60-06 INCREASE IN AFFERENT PELVIC NERVE FIRING DURING CONTINUOUS FILLING IN AN ISOLATED PERFUSED PORCINE BLADDER MODEL Devin Rogers, R. Hart Moore, Mina P. Ghatas, Christopher Bednarz, Gabrielle Grob, Michael Shields, Linda S. Burkett, Selvaraj Muthusamy, John E. Speich, and Adam P. Klausner Devin RogersDevin Rogers More articles by this author , R. Hart MooreR. Hart Moore More articles by this author , Mina P. GhatasMina P. Ghatas More articles by this author , Christopher BednarzChristopher Bednarz More articles by this author , Gabrielle GrobGabrielle Grob More articles by this author , Michael ShieldsMichael Shields More articles by this author , Linda S. BurkettLinda S. Burkett More articles by this author , Selvaraj MuthusamySelvaraj Muthusamy More articles by this author , John E. SpeichJohn E. Speich More articles by this author , and Adam P. KlausnerAdam P. Klausner More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003318.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: While urodynamics testing is routinely used to evaluate voiding dysfunction, the tests are expensive, invasive, poorly reproducible, and prone to artifacts. There is a pressing need to develop next-generation urodynamics. The purpose of this study was to develop an ex-vivo porcine bladder model to measure afferent pelvic nerve signaling that can be used as a platform for novel urodynamic tools. METHODS: Porcine bladders with attached ureters and vascular supply were harvested from local abattoirs and perfused with physiologic buffer. Micro-hook electrodes were attached to the pelvic nerve on the posterior of the bladder and electroneurogram (ENG) signals were recorded at 20KHz. Each bladder was filled with 1 liter of saline over 10 minutes using standard urodynamics equipment which simultaneously recorded intravesical pressure (Figure 1A). Nerve amplitude was calculated as the area under the curve (AUC) for each minute and nerve firing rate was calculated as number of nerve spikes (above baseline threshold) per minute. At the conclusion of the experiment, samples of the nerve were collected and processed for histological analysis (H&E and S100 stains). RESULTS: A total of 9 pig bladders were used. A pathologist confirmed the presence of nerve in all adequately processed samples. Vesical pressure, nerve firing rate, and nerve amplitude were all found to increase with bladder filling (Figure 1B). During filling tertiles (low fill: min 1-3, med fill: min 4-6, and high fill: min 7-10), pressures were 0.22±0.04, 0.38±0.05 and 0.72±0.07 (cmH20). Nerve firing rates were 0.08±0.03, 0.31±0.06 and 0.43±0.04 spikes/minute, respectively, and nerve amplitudes were 0.11±0.06, 0.39±0.06 and 0.56±0.14 μV. There were strong relationships between average normalized pressure values and averaged normalized nerve firing rate (r2=0.66) as well as average normalized nerve amplitude (r2=0.8). CONCLUSIONS: The ex-vivo perfused porcine bladder model can reproducibly measure afferent nerve activity that correlates with intravesical pressure during filling. This protocol can be used as a preclinical model for the development of next-generation urodynamics technologies and could potentially be used as a surrogate measure of bladder sensation. Source of Funding: NIH R01-DK101719 & VCU Endeavour Legacy Foundation © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e844 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Devin Rogers More articles by this author R. Hart Moore More articles by this author Mina P. Ghatas More articles by this author Christopher Bednarz More articles by this author Gabrielle Grob More articles by this author Michael Shields More articles by this author Linda S. Burkett More articles by this author Selvaraj Muthusamy More articles by this author John E. Speich More articles by this author Adam P. Klausner More articles by this author Expand All Advertisement PDF downloadLoading ...

Artificial TMAP Signal Generator Based on One-Bit Sigma Delta Modulator for MEC Test

The current study proposes three electrode-channels with time delay of artificial nerve signals generator utilized with only a active low pass filter and a Field Programmable Gate Array (FPGA). The XC3S100E FPGA board adopted to design a novel and real-time artificial transmembrane action potential (TMAP). The implementation of one bit Sigma Delta Modulation (SDM) method with linearized technique could be very expensive and complicated products with other technologies option currently available such as a microcontroller due to the fabrication requirements. This technique could employ in many biomedical applications and testing efficiently, especially, in evaluating the multi-electrode cuff system without requiring use of real nerves spike from animal models and saving time and effort, and cost. Moreover, this approach is adopted for further improvement to the signal performances such as resolution, accuracy, differential linearity monotonic DAC, and settling time of the signal waveform without extra hardware or cost required. In addition, the design included three channels of white Gaussian noise uncorrelated for each TMAP signal to simulate the real nerve noise environment, which surrounds the electrode cuff in experimental cases. A noise channels with adjustment level is added to the nerve spike using three sets of taps are employed to provide three channels of noise sources. The Xilinx ISE platform and Mentor Graphics ModelSim tool are used to simulate and implement this, and the results produced are compared. The power consumption of conventional technology is 31 mW, which is significantly higher than the power consumed (21mW) in modern technology. Furthermore, as compared to the usual way, the proposed solution conserved around 10% of the FPGA resources. This technique offers reuse in other applications where delay time, low amplitude voltage signals, and multichannel generator is needed. Moreover, this system offers adjustable waveform signal, noise level, conduction velocity and time delay easily to adequate different applications and tests.

Mammalian octopus cells are direction selective to frequency sweeps by excitatory synaptic sequence detection

Octopus cells are remarkable projection neurons of the mammalian cochlear nucleus, with extremely fast membranes and wide-frequency tuning. They are considered prime examples of coincidence detectors but are poorly characterized invivo. We discover that octopus cells are selective to frequency sweep direction, a feature that is absent in their auditory nerve inputs. In vivo intracellular recordings reveal that direction selectivity does not derive from across-frequency coincidence detection but hinges on the amplitudes and activation sequence of auditory nerve inputs tuned to clusters of hot spot frequencies. A simple biophysical octopus cell model excited with real nerve spike trains recreates direction selectivity through interaction of intrinsic membrane conductances with the activation sequence of clustered excitatory inputs. We conclude that octopus cells are sequence detectors, sensitive to temporal patterns across cochlear frequency channels. The detection of sequences rather than coincidences is a much simpler but powerful operation to extract temporal information.

Calcium/calmodulin-dependent protein kinase II associates with the K+ channel isoform Kv4.3 in adult rat optic nerve.

Spikes are said to exhibit “memory” in that they can be altered by spikes that precede them. In retinal ganglion cell axons, for example, rapid spiking can slow the propagation of subsequent spikes. This increases inter-spike interval and, thus, low-pass filters instantaneous spike frequency. Similarly, a K+ ion channel blocker (4-aminopyridine, 4AP) increases the time-to-peak of compound action potentials recorded from optic nerve, and we recently found that reducing autophosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII) does too. These results would be expected if CaMKII modulates spike propagation by regulating 4AP-sensitive K+ channels. As steps toward identifying a possible substrate, we test whether (i) 4AP alters optic nerve spike shape in ways consistent with reducing K+ current, (ii) 4AP alters spike propagation consistent with effects of reducing CaMKII activation, (iii) antibodies directed against 4AP-sensitive and CaMKII-regulated K+ channels bind to optic nerve axons, and (iv) optic nerve CaMKII co-immunoprecipitates with 4AP-sensitive K+ channels. We find that, in adult rat optic nerve, (i) 4AP selectively slows spike repolarization, (ii) 4AP slows spike propagation, (iii) immunogen-blockable staining is achieved with anti-Kv4.3 antibodies but not with antibodies directed against Kv1.4 or Kv4.2, and (iv) CaMKII associates with Kv4.3. Kv4.3 may thus be a substrate that underlies activity-dependent spike regulation in adult visual system pathways.

Vagus nerve spiking activity modulates prefrontal–amygdalar circuit related to anxiety

The vagus nerve has critical for brain-body interaction. It conveys internal physiological information from peripheral organs to the brain, causing interoception. Although numerous studies have shown that an alternation in vagal sensory input affects emotional states such as anxiety and depression, the mechanism by which vagus nerve activity is correlated with anxiety-related brain activity remains unknown. We have previously established a vagal spike recording method using a cuff-shaped electrode while simultaneously recording central and peripheral bioelectrical signals in freely moving rodents. In the present study, we investigated correlation between vagus nerve and anxiety-related brain activity on an elevated plus maze. We combined the recording method of vagus nerve with recording of local field potentials (LFPs) of the prefrontal cortex and the amygdala, which are crucial for expression of anxiety. Vagus nerve activity was negatively correlated with anxiety-related 4-7 Hz activity in the prefrontal cortex and the amygdala. The correlation was abolished by left cervical vagotomy. Chronic social defeat stress decorrelated vagus nerve activity with 4-7 Hz LFP oscillations. These results imply neurophysiological mechanisms underlying anxiolytic effects of vagus nerve stimulation and provide insights into neurophysiological underpinnings of the relationship between vagus nerve and emotion-related behavior.

Cytoskeletal Filaments Deep Inside a Neuron Are not Silent: They Regulate the Precise Timing of Nerve Spikes Using a Pair of Vortices

Hodgkin and Huxley showed that even if the filaments are dissolved, a neuron’s membrane alone can generate and transmit the nerve spike. Regulating the time gap between spikes is the brain’s cognitive key. However, the time modula-tion mechanism is still a mystery. By inserting a coaxial probe deep inside a neuron, we have re-peatedly shown that the filaments transmit electromagnetic signals ~200 μs before an ionic nerve spike sets in. To understand its origin, here, we mapped the electromagnetic vortex produced by a filamentary bundle deep inside a neuron, regulating the nerve spike’s electrical-ionic vortex. We used monochromatic polarized light to measure the transmitted signals beating from the internal components of a cultured neuron. A nerve spike is a 3D ring of the electric field encompassing the perimeter of a neural branch. Several such vortices flow sequentially to keep precise timing for the brain’s cognition. The filaments hold millisecond order time gaps between membrane spikes with microsecond order signaling of electromagnetic vortices. Dielectric resonance images revealed that ordered filaments inside neural branches instruct the ordered grid-like network of actin–beta-spectrin just below the membrane. That layer builds a pair of electric field vortices, which coherently activates all ion-channels in a circular area of the membrane lipid bilayer when a nerve spike propagates. When biomaterials vibrate resonantly with microwave and radio-wave, simultaneous quantum optics capture ultra-fast events in a non-demolition mode, revealing multiple correlated time-domain operations beyond the Hodgkin–Huxley paradigm. Neuron holograms pave the way to understanding the filamentary circuits of a neural network in addition to membrane circuits.

Relationship between oxygen consumption and neuronal activity in a defined neural circuit

BackgroundNeuronal computations related to sensory and motor activity along with the maintenance of spike discharge, synaptic transmission, and associated housekeeping are energetically demanding. The most efficient metabolic process to provide large amounts of energy equivalents is oxidative phosphorylation and thus dependent on O2 consumption. Therefore, O2 levels in the brain are a critical parameter that influences neuronal function. Measurements of O2 consumption have been used to estimate the cost of neuronal activity; however, exploring these metabolic relationships in vivo and under defined experimental conditions has been limited by technical challenges.ResultsWe used isolated preparations of Xenopus laevis tadpoles to perform a quantitative analysis of O2 levels in the brain under in vivo-like conditions. We measured O2 concentrations in the hindbrain in relation to the spike discharge of the superior oblique eye muscle-innervating trochlear nerve as proxy for central nervous activity. In air-saturated bath Ringer solution, O2 levels in the fourth ventricle and adjacent, functionally intact hindbrain were close to zero. Inhibition of mitochondrial activity with potassium cyanide or fixation of the tissue with ethanol raised the ventricular O2 concentration to bath levels, indicating that the brain tissue consumed the available O2. Gradually increasing oxygenation of the Ringer solution caused a concurrent increase of ventricular O2 concentrations. Blocking spike discharge with the local anesthetics tricaine methanesulfonate diminished the O2 consumption by ~ 50%, illustrating the substantial O2 amount related to neuronal activity. In contrast, episodes of spontaneous trochlear nerve spike bursts were accompanied by transient increases of the O2 consumption with parameters that correlated with burst magnitude and duration.ConclusionsControlled experimental manipulations of both the O2 level as well as the neuronal activity under in vivo-like conditions allowed to quantitatively relate spike discharge magnitudes in a particular neuronal circuitry with the O2 consumption in this area. Moreover, the possibility to distinctly manipulate various functional parameters will yield more insight in the coupling between metabolic and neuronal activity. Thus, apart from providing quantitative empiric evidence for the link between physiologically relevant spontaneous spike discharge in the brain and O2-dependent metabolism, isolated amphibian preparations are promising model systems to further dissociate the O2 dynamics in relation to neuronal computations.

Dual real-time in vivo monitoring system of the brain-gut axis

The brain–gut axis which is an interaction between recognition and emotion and the gut sensory system for food and microbiota is important for health. However, there is no real-time monitoring system of the brain and the gut simultaneously so far. We attempted to establish a dual real-time monitoring system for the brain–gut axis by a combination of intravital Ca2+ imaging of the gut and electroencephalogram. Using a conditional Yellow Cameleon 3.60 expression mouse line, we performed intravital imaging of the gut, electrophysiological recordings of the vagus nerve, and electroencephalogram recordings of the various cortical regions simultaneously upon capsaicin stimuli as a positive control. Upon capsaicin administration into the small intestinal lumen, a simultaneous response of Ca2+ signal in the enteric nervous system and cortical local field potentials (LFPs) was successfully observed. Both of them responded immediately upon capsaicin stimuli. Capsaicin triggered a significant increase in the frequency of vagus nerve spikes and a significant decrease in the slow-wave power of cortical LFPs. Furthermore, capsaicin induced delayed and sustained Ca2+ signal in intestinal epithelial cells and then suppressed intestinal motility. The dual real-time monitoring system of the brain and the gut enables to dissect the interaction between the brain and the gut over time with precision.

Anlaysis of multiple organ interactions by recordings and manipulations of vagus nerve spiking activity

Anlaysis of multiple organ interactions by recordings and manipulations of vagus nerve spiking activity

自由行動下げっ歯動物における迷走神経の投射方向選択的な生理機能の解析

自由行動下げっ歯動物における迷走神経の投射方向選択的な生理機能の解析

Sniffing behaviour‐related changes in cardiac and cortical activity in rats

High-frequency (HF) sniffing represents active odour sampling and an increase in the animal's motivation. We examined how HF sniffing affects the physiological activity of the brain-body system. During HF sniffing, heart rates and the ratio of theta to delta critical local field potential power were comparable to those observed during motion periods. Vagus nerve spike rates did not vary depending on HF sniffing. Our results suggest that physiological factors in the central nervous system and the periphery are not simply determined by locomotion but are crucially associated with HF sniffing. Sniffing is a fundamental behaviour for odour sampling, and high-frequency (HF) sniffing, generally at a sniff frequency of more than 6Hz, is considered to represent an animal's increased motivation to explore external environments. Here, we examined how HF sniffing is associated with changes in physiological signals from the central and peripheral organs in rats. During HF sniffing while the rats were stationary, heart rates, the magnitude of dorsal neck muscle contraction, and the ratio of theta to delta local field potential power in the motor cortex were comparable to those observed during motion periods and were significantly higher than those observed during resting respiration periods. No pronounced changes in vagus nerve spike rates were detected in relation to HF sniffing. These results demonstrate that central and peripheral physiological factors are crucially associated with the emergence of HF sniffing, especially during quiescent periods. Behavioural data might be improved to more accurately evaluate an animal's internal psychological state if they are combined with a sniffing pattern as a physiological marker.

Integrating a brain into a bat robot

The sophisticated biosonar systems of horseshoe bats have enabled these animals to navigate and pursue prey in complex environments. A conspicuous peripheral dynamics in which the animals' noseleaves and pinnae change during biosonar behaviors could play an important role in enabling these capabilities. It may be hypothesized that for the integration between peripheral dynamics and neural signal processing/estimation to be maximally effective, the periphery should be controlled by feedback from the output of the subsequent neural echo processing. In the way, the specifics of sensory information encoding in the periphery could be controlled based on the needs of the neural signal processing. As a first step towards such an integration in a biomimetic sonar head, a computational model for the inner ear and the auditory nerve's spike code has been integrated with a dynamic periphery that—like the computational models—mimics horseshoe bats. For each model stage, alternative versions with different levels of complexity have been implemented to test how module complexity and the values of the associated parameters affect the capacity of the echo representation to encode sensory information. These effects have been tested based on a large dataset of 220 000 echoes collected in natural forest environments.

Analysis of mental states based on peripheral organ activity

Behavioral tests using rodents are widely used for assessing mental states of animals and the effects of pharmacological drugs on psychiatric disorders. However, the results of behavioral tests are sometimes inconsistent due to individual differences. To evaluate animal's mental states based on internal organ activity, we recently developed a new electrophysiological method to simultaneously monitor cortical local field potentials, electrocardiograms, electromyograms, respiratory signals, and vagus nerve spikes in a freely moving rodent. Here, we introduce some results obtained from an elevated plus maze test. Both cortical activity patterns and vagus nerve spike patterns are crucially related to other peripheral organ activity rather than arm types of the maze in which animal were located, which demonstrates that combining behavioral tests with peripheral physiological makers enables a more accurate evaluation of rodent mental states. Moreover, we show that functional connection patterns across cortical regions could be predictive factors accounting for stress susceptibility defined based on the irregularity of heartbeat signals, demonstrating that cortical activity may be a mechanism that causes abnormal activity of peripheral organs in response to mental stress episodes. These observations from our recording technique are a new step for understanding of the neurophysiological correlates of mind-body associations in health and disease.

Vagus nerve spiking activity associated with locomotion and cortical arousal states in a freely moving rat.

The vagus nerve serves as a central pathway for communication between the central and peripheral organs. Despite traditional knowledge of vagus nerve functions, detailed neurophysiological dynamics of the vagus nerve in naïve behavior remain to be understood. In this study, we developed a new method to record spiking patterns from the cervical vagus nerve while simultaneously monitoring central and peripheral organ bioelectrical signals in a freely moving rat. When the rats transiently elevated locomotor activity, the frequency of vagus nerve spikes was correspondingly increased, and this activity was retained for several seconds after the increase in running speed terminated. Spike patterns of the vagus nerve were not robustly associated with which arms the animals entered on an elevated plus maze. During sniffing behavior, vagus nerve spikes were nearly absent. During stopping, the vagus nerve spike patterns differed considerably depending on external contexts and peripheral activity states associated with cortical arousal levels. Stimulation of the vagus nerve altered rat's running speed and cortical arousal states depending on running speed at the instant of stimulation. These observations are a new step for uncovering the physiological dynamics of the vagus nerve modulating the visceral organs such as cardiovascular, respiratory, and gastrointestinal systems.

Hydrogen sulfide downregulates colonic afferent sensitivity by a nitric oxide synthase-dependent mechanism in mice.

The effect of hydrogen sulfide (H2 S) on visceral nociception is elusive. The conflicting evidence of its pro- and antinociceptive effects raises a series of questions with respect to the effect of H2 S on colonic afferent activity and the underlying mechanism, which was further elucidated in this study. Colonic mesenteric afferent nerve spikes of normal male C57BL/6J mice, Cbs+/- mice, and Wistar rats were recorded in vitro. The abdominal withdrawal reflex (AWR) induced by colorectal distension (CRD) was evaluated in Cbs+/- mice and WT littermates. Sodium hydrosulfide (NaHS) significantly decreased colonic afferent spontaneous discharge, chemosensitivity to bradykinin, mechanosensitivity to ramp distention, and intraluminal pressure in mice. Reducing the relaxant action of NaHS on intestinal smooth muscle using the nonspecific K+ channel blocker TEA (10mmol/L) did not block the inhibition of NaHS on afferent nerve activity. The inhibitory effects of NaHS (0.5mmol/L) on colonic afferent sensitivity were largely eliminated by the pretreatment with nonspecific NOS inhibitor NG -Methyl-l-arginine acetate salt (1mmol/L), the specific nNOS inhibitor NPLA (1μmol/L), or N-type Ca2+ channel blocker ω-conotoxin GVIA (1μmol/L). Compared with WT mice, Cbs+/- mice showed increased mesenteric afferent sensitivity to colonic distention and enhanced hyperalgesic response to CRD. Intraperitoneal administration of NaHS (60μmol/kg) alleviated the nociception response to CRD in both Cbs+/- and WT mice. H2 S downregulates colonic mesenteric afferent sensitivity by a nNOS-dependent mechanism in mice. Our findings may demonstrate a new mechanism for the antinociceptive effect of H2 S in colon.