Sensory Excitation Research Articles

Evaluation of Peripheral Neuropathy in Rat Models of Metabolic Syndrome and Diabetes Mellitus.

The dynamics of nephropathy development in rats with type 2 diabetes mellitus, caused by a high-fat diet and the streptozotocin administration (25 mg/kg), and metabolic syndrome, caused by addition of 20% fructose solution to the diet, was evaluated during the experiment. Models with moderate severity of metabolic changes without significant changes in body weight were obtained after 24 weeks. To study neuropathy severity, the method of electroneuromyography was used; the velocities of motor and sensory excitation propagation along the caudal nerve fibers were measured. In modeled diabetes mellitus against the background of hyperglycemia, a marked decrease in motor and sensory propagation rates was observed, and an increase in the response durations was noted from week 12 to week 24, indicating pronounced neuropathy. In the fructose model, the motor response duration increased from week 12, which possibly indicates the development of peripheral neuropathy.

Lateral inhibition in V1 controls neural & perceptual contrast sensitivity.

Lateral inhibition is a central principle for sensory system function. It is thought to operate by the activation of inhibitory neurons that restrict the spatial spread of sensory excitation. Much work on the role of inhibition in sensory systems has focused on visual cortex; however, the neurons, computations, and mechanisms underlying cortical lateral inhibition remain debated, and its importance for visual perception remains unknown. Here, we tested how lateral inhibition from PV or SST neurons in mouse primary visual cortex (V1) modulates neural and perceptual sensitivity to stimulus contrast. Lateral inhibition from PV neurons reduced neural and perceptual sensitivity to visual contrast in a uniform subtractive manner, whereas lateral inhibition from SST neurons more effectively changed the slope (or gain) of neural and perceptual contrast sensitivity. A neural circuit model identified spatially extensive lateral projections from SST neurons as the key factor, and we confirmed this with anatomy and direct subthreshold measurements of a larger spatial footprint for SST versus PV lateral inhibition. Together, these results define cell-type specific computational roles for lateral inhibition in V1, and establish their unique consequences on sensitivity to contrast, a fundamental aspect of the visual world.

Early Auditory Processing Predicts Efficient Working Memory Functioning in Schizophrenia.

Early auditory processing (EAP) deficits have been consistently documented in individuals diagnosed with schizophrenia (SZ). However, a relationship between EAP and executive attention has not been confirmed in SZ versus healthy controls (HC). The current study aimed to demonstrate that unlike HC, in SZ patients, auditory change-detection event-related potentials (ERPs) are significantly associated with executive working memory (WM) functioning. Additionally, correlational analyses investigated the relationships between patients’ auditory ERPs, WM performance, and schizophrenia symptom severity scores. We examined verbal WM accuracy associated with “executive-control” prefrontal cortex mechanisms and EAP ERPs under midline prefrontal electrodes in 12 SZ patients versus 12 demographically matched HC. Mismatch negativity (MMN) amplitudes and latencies in SZ patients were not significantly different from HC, however, their verbal WM performance was significantly impaired versus HC. Importantly, prolonged MMN latencies in the SZ group were correlated with better WM accuracy. In the HC group, WM accuracy was unrelated to MMN latencies. Patients’ MMN parameters were unrelated to schizophrenia symptom-domain severity. However, patients’ WM RTs and accuracy were significantly related to illness severity and negative symptom severity, respectively. Therefore, inefficient sensory excitation related to EAP timing may underlie poor executive verbal WM functioning and might indirectly exacerbate the severity of negative symptoms in SZ. Treatments targeting prefrontal cortex dysfunction in schizophrenia are discussed.

Predicting thermal pleasure experienced in dynamic environments from simulated cutaneous thermoreceptor activity.

Research into human thermal perception indoors has focused on "neutrality" under steady-state conditions. Recent interest in thermal alliesthesia has highlighted the hedonic dimension of our thermal world that has been largely overlooked by science. Here, we show the activity of sensory neurons can predict thermal pleasure under dynamic exposures. A numerical model of cutaneous thermoreceptors was applied to skin temperature measurements from 12 human subjects. A random forest model trained on simulated thermoreceptor impulses could classify pleasure responses (F1 score of 67%) with low false positives/negatives (4%). Accuracy increased (83%) when excluding the few extreme (dis)pleasure responses. Validation on an independent dataset confirmed model reliability. This is the first empirical demonstration of the relationship between thermoreceptors and pleasure arising from thermal stimuli. Insights into the neurophysiology of thermal perception can enhance the experience of built environments through designs that promote sensory excitation instead of neutrality.

Steinach. Ueber die centripetale Erregungsleitung im Bereiche des Spinalganglions. (On the centripetal conduction of excitation along the dorsal nodes). - Arch of Pfluger. Bd. 78, p. 291

According to the generally accepted view, sensory excitation in the spinal nerve system reaches the spinal cord through the nerve cells of the dorsal nodes, which from this point of view with full right can be attributed to the category of sensitive nerve cells. Working in the early 90s on the issue of negative fluctuations, Steinach came across a fact that remained completely inexplicable for him until the last day.

H2S Contributes to Carotid Body Response to Hypoxia but Not Anoxia

We previously reported that cystathionine‐γ‐lyase (CSE)‐derived H2S mediates carotid body (CB) response to hypoxia (Hx) (Peng et al., PNAS, 2010). A recent study showed that CB Type I cell responses to anoxia (Ax) were unaffected by CSE inhibitors (Kim et al. Respir Physiology, 2015). We re‐examined the role of CSE‐derived H2S in CB sensory and Type I cell responses to Hx and Ax in adult Sprague‐Dawley rats, wild‐type and CSE knockout (KO) mice. Hx (pO2=37± 3mmHg) produced robust sensory excitation, and increased H2S levels in the CB; whereas Ax (pO2 =5±4 mmHg) produced only a weak sensory excitation and had no effect on H2S levels. Ax evoked a robust [Ca2+]i response of Type I cells as compared to hypoxia. CSE inhibitor DL‐propargylglycine (DL‐PAG, 50μM) inhibited Hx but not Ax‐evoked sensory and Type I responses. Higher concentration (300μM) of DL‐PAG alone, or in combination with aminooxyacetic acid (300μM), non‐selectively blocked [Ca2+]i responses of Type I cells to Ax and decreased cell viability. CB sensory excitation and [Ca2+]i elevation in Type I cells were unaffected in CSE null mice as compared to wild‐type (Wt) mice. Breathing stimulation by Hx was absent in CSE KO mice, whereas depressed breathing by Ax was unaffected. These observations suggest that CSE‐derived H2S contributes to carotid body response to “physiologically” relevant hypoxia but not to anoxia.Support or Funding InformationSupported by National Institutes of Health grants P01‐HL‐90554This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Impaired Acute Hypoxic Sensing in Olfactory Receptor 78 Knockout Mice

Chang et al. (2015) reported that olfactory receptor 78 knockout (Olfr78 KO) mice exhibit impaired breathing and carotid body (CB) responses to hypoxia. However, a recent study questioned this finding (Lopez‐Barneo et al. 2018). To resolve the controversy, present study was performed on age and gender matched wild‐type (WT) and Olfr78 KO mice on Bl6 and Jax background strains (n=10 mice each genotype). Breathing was monitored in conscious mice by plethysmography and expressed as minute ventilation; VE/VO2, as well as by recording phrenic nerve activity (minute neural respiration; MNR, AU) in anesthetized mice. Hypoxia (12%O2)‐evoked increase in VE/VO2 and MNR were significantly attenuated in Olfr78 KO mice on Bl6 and Jax backgrounds, respectively as compared to WT mice (p<0.01). Hypoxia (pO2 ~35mmHg)–induced CB sensory excitation was 61 and 43% less in Olfr78‐Bl6 and Jax, respectively as compared to WT mice (p<0.01), and this effect was associated with 78% reduction in [Ca2+]i response of CB glomus cells to hypoxia (p< 0.01). In contrast, breathing and CB sensory nerve responses to 10%CO2 were comparable between Olfr78 KO (both Bl6 and Jax) and WT mice. These findings demonstrate that Olfr78 KO mice have impaired breathing, CB sensory, and glomus cell responses to acute hypoxia.Support or Funding InformationSupported by NIH‐HLBI P01‐HL‐90554This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

H2S mediates carotid body response to hypoxia but not anoxia

The role of cystathionine-γ-lyase (CSE) derived H2S in the hypoxic and anoxic responses of the carotid body (CB) were examined. Experiments were performed on Sprague-Dawley rats, wild type and CSE knockout mice on C57BL/6 J background. Hypoxia (pO2 = 37 ± 3 mmHg) increased the CB sensory nerve activity and elevated H2S levels in rats. In contrast, anoxia (pO2 = 5 ± 4 mmHg) produced only a modest CB sensory excitation with no change in H2S levels. DL-propargylglycine (DL-PAG), a blocker of CSE, inhibited hypoxia but not anoxia-evoked CB sensory excitation and [Ca2+]i elevation of glomus cells. The inhibitory effects of DL-PAG on hypoxia were seen: a) when it is dissolved in saline but not in dimethyl sulfoxide (DMSO), and b) in glomus cells cultured for18 h but not in cells either soon after isolation or after prolonged culturing (72 h) requiring 1–3 h of incubation. On the other hand, anoxia-induced [Ca2+]i responses of glomus cell were blocked by high concentration of DL-PAG (300μM) either alone or in combination with aminooxyacetic acid (AOAA; 300μM) with a decreased cell viability. Anoxia produced a weak CB sensory excitation and robust [Ca2+]i elevation in glomus cells of both wild-type and CSE null mice. As compared to wild-type, CSE null mice exhibited impaired CB chemo reflex as evidenced by attenuated efferent phrenic nerve responses to brief hyperoxia (Dejours test), and hypoxia. Inhalation of 100% N2 (anoxia) depressed breathing in both CSE null and wild-type mice. These observations demonstrate that a) hypoxia and anoxia are not analogous stimuli for studying CB physiology and b) CSE-derived H2S contributes to CB response to hypoxia but not to that of anoxia.

Simultaneous activation of parallel sensory pathways promotes a grooming sequence in Drosophila.

A central model that describes how behavioral sequences are produced features a neural architecture that readies different movements simultaneously, and a mechanism where prioritized suppression between the movements determines their sequential performance. We previously described a model whereby suppression drives a Drosophila grooming sequence that is induced by simultaneous activation of different sensory pathways that each elicit a distinct movement (Seeds et al., 2014). Here, we confirm this model using transgenic expression to identify and optogenetically activate sensory neurons that elicit specific grooming movements. Simultaneous activation of different sensory pathways elicits a grooming sequence that resembles the naturally induced sequence. Moreover, the sequence proceeds after the sensory excitation is terminated, indicating that a persistent trace of this excitation induces the next grooming movement once the previous one is performed. This reveals a mechanism whereby parallel sensory inputs can be integrated and stored to elicit a delayed and sequential grooming response.

Tasting arterial blood: what do the carotid chemoreceptors sense?

The carotid bodies are sensory organs that detect the chemical composition of the arterial blood. The carotid body sensory activity increases in response to arterial hypoxemia and the ensuing chemoreflex regulates vital homeostatic functions. Recent studies suggest that the carotid bodies might also sense arterial blood glucose and circulating insulin levels. This review focuses on how the carotid bodies sense O2, glucose, and insulin and some potential implications of these sensory functions on physiological regulation and in pathophysiological conditions. Emerging evidence suggests that carbon monoxide (CO)-regulated hydrogen sulfide (H2S), stemming from hypoxia, depolarizes type I cells by inhibiting certain K+ channels, facilitates voltage-gated Ca2+ influx leading to sensory excitation of the carotid body. Elevated CO and decreased H2S renders the carotid bodies insensitive to hypoxia resulting in attenuated ventilatory adaptations to high altitude hypoxia, whereas reduced CO and high H2S result in hypersensitivity of the carotid bodies to hypoxia and hypertension. Acute hypoglycemia augments the carotid body responses to hypoxia but that a prolonged lack of glucose in the carotid bodies can lead to a failure to sense hypoxia. Emerging evidence also indicates that carotid bodies might sense insulin directly independent of its effect on glucose, linking the carotid bodies to the pathophysiological consequences of the metabolic syndrome. How glucose and insulin interact with the CO-H2S signaling is an area of ongoing study.

Decision criterion dynamics in animals performing an auditory detection task.

Classical signal detection theory attributes bias in perceptual decisions to a threshold criterion, against which sensory excitation is compared. The optimal criterion setting depends on the signal level, which may vary over time, and about which the subject is naïve. Consequently, the subject must optimise its threshold by responding appropriately to feedback. Here a series of experiments was conducted, and a computational model applied, to determine how the decision bias of the ferret in an auditory signal detection task tracks changes in the stimulus level. The time scales of criterion dynamics were investigated by means of a yes-no signal-in-noise detection task, in which trials were grouped into blocks that alternately contained easy- and hard-to-detect signals. The responses of the ferrets implied both long- and short-term criterion dynamics. The animals exhibited a bias in favour of responding “yes” during blocks of harder trials, and vice versa. Moreover, the outcome of each single trial had a strong influence on the decision at the next trial. We demonstrate that the single-trial and block-level changes in bias are a manifestation of the same criterion update policy by fitting a model, in which the criterion is shifted by fixed amounts according to the outcome of the previous trial and decays strongly towards a resting value. The apparent block-level stabilisation of bias arises as the probabilities of outcomes and shifts on single trials mutually interact to establish equilibrium. To gain an intuition into how stable criterion distributions arise from specific parameter sets we develop a Markov model which accounts for the dynamic effects of criterion shifts. Our approach provides a framework for investigating the dynamics of decisions at different timescales in other species (e.g., humans) and in other psychological domains (e.g., vision, memory).

CaV3.2 T-type Ca²⁺ channels in H₂S-mediated hypoxic response of the carotid body.

Arterial blood O2 levels are detected by specialized sensory organs called carotid bodies. Voltage-gated Ca(2+) channels (VGCCs) are important for carotid body O2 sensing. Given that T-type VGCCs contribute to nociceptive sensation, we hypothesized that they participate in carotid body O2 sensing. The rat carotid body expresses high levels of mRNA encoding the α1H-subunit, and α1H protein is localized to glomus cells, the primary O2-sensing cells in the chemoreceptor tissue, suggesting that CaV3.2 is the major T-type VGCC isoform expressed in the carotid body. Mibefradil and TTA-A2, selective blockers of the T-type VGCC, markedly attenuated elevation of hypoxia-evoked intracellular Ca(2+) concentration, secretion of catecholamines from glomus cells, and sensory excitation of the rat carotid body. Similar results were obtained in the carotid body and glomus cells from CaV3.2 knockout (Cacna1h(-/-)) mice. Since cystathionine-γ-lyase (CSE)-derived H2S is a critical mediator of the carotid body response to hypoxia, the role of T-type VGCCs in H2S-mediated O2 sensing was examined. Like hypoxia, NaHS, a H2S donor, increased intracellular Ca(2+) concentration and augmented carotid body sensory nerve activity in wild-type mice, and these effects were markedly attenuated in Cacna1h(-/-) mice. In wild-type mice, TTA-A2 markedly attenuated glomus cell and carotid body sensory nerve responses to hypoxia, and these effects were absent in CSE knockout mice. These results demonstrate that CaV3.2 T-type VGCCs contribute to the H2S-mediated carotid body response to hypoxia.

Comparison impact of sensory excitation performed by family members and nurses on the level of consciousness in patients who are admitted to Intensive Care Unit

Background: Appropriate sensory excitation can improve brain synaptic contact and establish consciousness. Aim: The aim of this study was to investigate the sensory excitation delivered by family members and nurses on the level of consciousness in patients who are admitted to ICU. Method: In this clinical trial, 69 patients admitted to ICU in Ashair and Shafa Hospital, Khorammabad, were randomly assigned into two interventions and one control group. The first intervention group received sensory excitation by family members, and the second intervention group by the nurses. Control group were not received any intervention. Intervention was applied two hours a day at 4-5 pm and 8-9 pm to the intervention groups for six days. For all subjects in these three groups, the level of consciousness was measured twice at 5 minutes before and 30 minutes after intervention by the research assistant using Glasgow Coma Scale (GCS). The data were analyzed by SPSS software version 18 using repeated measures and ANOVA tests. Results: A significant discrepancy was observed between experimental groups in average increasing in GCS before and after intervention based on covariance analysis test results (P<0.001). In addition, the first intervention groups showed the higher increase in GCS score (0.388±0.032 units) and the second intervention the moderate increase (0.268±0.032 units). The lowest increase was found in control group (0.44±0.032 units). Conclusion: Sensory excitation performed by family members is more effective to improve the level of consciousness of coma patients than the nurses, thus it is suggested to provide conditions in which the nearest family members can do the sensitive excitation program for patients hospitalized in ICU ward subject to receiving adequate training.

Gaseous messengers in oxygen sensing

The carotid body is a sensory organ that detects acute changes in arterial blood oxygen (O(2)) levels and reflexly mediates systemic cardiac, vascular, and respiratory responses to hypoxia. This article provides a brief update of the roles of gas messengers as well as redox homeostasis by hypoxia-inducible factors (HIFs) in hypoxic sensing by the carotid body. Carbon monoxide (CO) and nitric oxide (NO), generated by heme oxygenase-2 (HO-2) and neuronal nitric oxide synthase (nNOS), respectively, inhibit carotid body activity. Molecular O(2) is a required substrate for the enzymatic activities of HO-2 and nNOS. Stimulation of carotid body activity by hypoxia may reflect reduced formation of CO and NO. Glomus cells, the site of O(2) sensing in the carotid body, express cystathionine γ-lyase (CSE), an H(2)S generating enzyme. Cth ( -/- ) mice, which lack CSE, exhibit severely impaired hypoxia-induced H(2)S generation, sensory excitation, and stimulation of breathing in response to low O(2). Hypoxia-evoked H(2)S generation in the carotid body requires the interaction of CSE with HO-2, which generates CO. Carotid bodies from Hif1a ( +/- ) mice with partial HIF-1α deficiency do not respond to hypoxia, whereas carotid bodies from mice with partial HIF-2α deficiency are hyper-responsive to hypoxia. The opposing roles of HIF-1α and HIF-2α in the carotid body have provided novel insight into molecular mechanisms of redox homeostasis and its role in hypoxia sensing. Heightened carotid body activity has been implicated in the pathogenesis of autonomic morbidities associated with sleep-disordered breathing, congestive heart failure, and essential hypertension. The enzymes that generate gas messengers and redox regulation by HIFs represent potential therapeutic targets for normalizing carotid body function and downstream autonomic output in these disease states.

Neocortical Interneurons: From Diversity, Strength

Interneurons in the neocortex of the brain are small, locally projecting inhibitory GABAergic cells with a broad array of anatomical and physiological properties. The diversity of interneurons is believed to be crucial for regulating myriad operations in the neocortex. Here, we describe current theories about how interneuron diversity may support distinct neocortical processes that underlie perception.

Peripheral sensory activation of cortical circuits in the leg motor cortex of man

Peripheral sensory afferents in the hand activate both excitatory and inhibitory intracortical circuits to potentially facilitate and prune descending motor commands. In this study, we characterized how afferent inputs modulate the excitability of cortical circuits in the leg area of the primary motor cortex by examining how stimulation of the tibial nerve (TN) at the ankle alters motor evoked potentials (MEPs) activated by transcranial magnetic stimulation (TMS). Resting MEPs in the tibialis anterior (TA) muscle were facilitated in response to heteronymous activation of the TN 45-50 ms earlier, whereas MEPs were inhibited at interstimulus intervals of 32.5-37.5 ms. Similar time-dependent modulation occurred in the soleus (SOL) muscle with stimulation of the homonymous posterior tibial nerve (PTN) at the knee. To determine the site of this afferent-evoked facilitation and inhibition (spinal or cortical), we compared the effects of afferent stimulation to responses evoked at subcortical sites. At interstimulus intervals where MEP facilitation was observed (near 50 ms), spinal H-reflexes and responses evoked from corticospinal tract stimulation at the brainstem were predominantly depressed by the sensory stimulus suggesting that the observed MEP facilitation was cortical in origin. At interstimulus intervals where MEP depression was observed (near 35 ms), brainstem evoked responses were depressed to a similar degree and, in contrast to the hand, this suggests that spinal rather than cortical circuits mediate short-latency afferent inhibition (SAI) of leg MEPs. When the MEP was facilitated by afferent inputs, short-interval intracortical inhibition (SICI) was reduced and intracortical facilitation (ICF) was increased, but long-interval intracortical inhibition (LICI) at a 100 ms interval was unchanged. In addition, sensory excitation increased the recruitment of early, middle and late descending corticospinal volleys as evidenced from increases in MEP facilitation at the corresponding I-wave periodicity. We propose that sensory activation from the leg has a diffuse and predominantly facilitatory effect on the leg primary motor cortex.

5‐HT evokes sensory long‐term facilitation of rodent carotid body via activation of NADPH oxidase

5-Hydroxytryptamine (5-HT) evokes long-term activation of neuronal activity in the nervous system. Carotid bodies, the sensory organs for detecting arterial oxygen, express 5-HT. In the present study we examined whether 5-HT evokes sensory long-term facilitation (LTF) of the carotid body, and if so by what mechanism(s). Experiments were performed on anaesthetized adult rats and mice. Sensory activity was recorded from carotid bodies ex vivo. Spaced (3 x 15 s of 100 nm at 5 min intervals) but not mass (300 nm, 45 s) application of 5-HT elicited LTF, whereas both modes of 5-HT application evoked initial sensory excitation of the carotid bodies in rats. Ketanserin, a 5-HT(2) receptor antagonist prevented sensory LTF but not the initial sensory excitation. Spaced application of 5-HT activated protein kinase C (PKC) as evidenced by increased phosphorylations of PKC at Thr(514) and myristoylated alanine-rich C kinase substrate (MARCKS) and these effects were abolished by ketanserin as well as bisindolylmaleimide (Bis-1), an inhibitor of PKC. Bis-1 prevented 5-HT-evoked sensory LTF. 5-HT increased NADPH oxidase activity and PKC-dependent phosphorylation of p47(phox) subunit of the oxidase complex. NADPH oxidase inhibitors (apocynin and diphenyl iodinium), as well as an anti-oxidant (N-acetyl cysteine), prevented 5-HT-evoked sensory LTF. Mice deficient in gp91(phox), the membrane subunit of the NADPH oxidase complex, showed no sensory LTF, although responding to 5-HT with initial afferent nerve activation, whereas both LTF and initial excitation by 5-HT were seen in wild-type mice. These results demonstrate that spaced but not mass application of 5-HT elicits sensory LTF of the carotid body via activation of 5-HT(2) receptors, which involves a novel signalling mechanism coupled to PKC-dependent activation of NADPH oxidase.

P2X purinoceptors and sensory transmission

The involvement of P2X purinoreceptors (P2X receptors) in somatosensory transmission is herein reviewed with a focus on those receptors that are expressed on sensory neurons to elucidate their roles in the initiation of sensory excitation from primary afferent neurons, in modulating synaptic transmission at the first sensory synapses formed between primary afferent central terminals and dorsal horn neurons, in directly mediating sensory synaptic transmission to the spinal cord dorsal horn, and in modulating synaptic transmission among spinal cord dorsal horn neurons. Research on P2X receptors has indicated that these receptors play a significant role in both physiological and pathological pain states. As a result, P2X receptors may serve as therapeutic targets for the treatment of pathological pain conditions associated with nerve injury, tissue inflammation, cancer, and other diseases.

Cellular stoichiometry of the components of the chemotaxis signaling complex.

The chemotactic sensory system of Escherichia coli comprises membrane-embedded chemoreceptors and six soluble chemotaxis (Che) proteins. These components form signaling complexes that mediate sensory excitation and adaptation. Previous determinations of cellular content of individual components provided differing and apparently conflicting values. We used quantitative immunoblotting to perform comprehensive determinations of cellular amounts of all components in two E. coli strains considered wild type for chemotaxis, grown in rich and minimal media. Cellular amounts varied up to 10-fold, but ratios between proteins varied no more than 30%. Thus, cellular stoichiometries were almost constant as amounts varied substantially. Calculations using those cellular stoichiometries and values for in vivo proportions of core components in complexes yielded an in vivo stoichiometry for core complexes of 3.4 receptor dimers and 1.6 CheW monomers for each CheA dimer and 2.4 CheY, 0.5 CheZ dimers, 0.08 CheB, and 0.05 CheR per complex. The values suggest a core unit of a trimer of chemoreceptor dimers, a dimer (or two monomers) of kinase CheA, and two CheW. These components may interact in extended arrays and, thus, stoichiometries could be nonintegral. In any case, cellular stoichiometries indicate that CheY could be bound to all signaling complexes and this binding would recruit essentially the entire cellular complement of unphosphorylated CheY, and also that phosphatase CheZ, methylesterase CheB, and methyltransferase CheR would be present at 1 per 2, per 14, and per 20 core complexes, respectively. These characteristic ratios will be important in quantitative treatments of chemotaxis, both experimental and theoretical.

Spreading sensory excitation

Integration and crosstalk between the signals carried by different primary afferent neurones occurs mainly in the CNS. In its simplest forms, this integration occurs as a result of the convergence of different axon terminals on the same second-order afferent neurones, or through axo–axonic synapses mediating presynaptic inhibition or excitation. A new concept has emerged recently, following the discovery that the electrical stimulation of peripheral branches of dorsal root ganglion (DRG) cells induced excitation of the soma not only of the stimulated neurones but also of neighbouring DRG cells within the same ganglion, despite lack of evidence for synaptic contacts between the somata of DRG cells. This phenomenon has been defined as cross-depolarization (CD) or cross-excitation. A recent study [ 1. Oh E.J. Weinreich D. Chemical communication between vagal afferent somata in nodose ganglia of the rat and the guinea-pig in vitro. J. Neurophysiol. 2002; 37: 2801-2807 Google Scholar ] now shows that ganglion cells associated with cranial nerves (e.g. the nodose ganglion associated with the vagal afferents) also display CD, demonstrating that this phenomenon is widespread among primary afferent neurones.