Electrophysiology

Disruptions in sleep/wake cycles, including decreased amplitude of rhythmic behaviors and fragmentation of the sleep episodes, are commonly associated with aging in humans and other mammals. While there are undoubtedly many factors contributing to these changes, a body of literature is emerging, suggesting that an age-related decline in the central circadian clock in the suprachiasmatic nucleus (SCN) may be a key element responsible. To explore age-related changes in the SCN, we have performed in vivo multiunit neural activity (MUA) recordings from the SCN of freely moving young (3-5 months) and middle-aged (13-18 months) mice. Importantly, the amplitude of day-night difference in MUA was significantly reduced in the older mice. We also found that the neural activity rhythms are clearly degraded in the subparaventricular zone, one of the main neural outputs of the SCN. Surprisingly, parallel studies indicate that the molecular clockwork in the SCN as measured by PER2 exhibited only minor deficits at this same age. Thus, the circadian output measured at the level of neural activity rhythms in the SCN is degraded by aging, and this decline occurs before the disruption of key components of the molecular clockwork.

Two studies were carried out to assess the applicability of echoplanar fMRI at 3.0 T to the analysis of somatosensory mechanisms in humans. Vibrotactile stimulation of the tips of digits two and five reliably generated significant clusters of activation in primary (SI) and secondary (SII) somatosensory cortex, area 43, the pre-central gyrus, posterior insula, posterior parietal cortex and posterior cingulate. Separation of these responses by digit in SI was possible in all subjects and the activation sites reflected the known lateral position of the representation of digit 2 relative to that of digit 5. A second study employed microneurographic techniques in which individual median-nerve mechanoreceptive afferents were isolated, physiologically characterized, and microstimulated in conjunction with fMRI. Hemodynamic responses, observed in every case, were robust, focal, and physiologically orderly. These techniques will enable more detailed studies of the representation of the body surface in human somatosensory cortex, the relationship of that organization to short-term plasticity in responses to natural tactile stimuli, and effects of stimulus patterning and unimodal/cross-modal attentional manipulations. They also present unique opportunities to investigate the basic physiology of the BOLD effect, and to optimize the operating characteristics of two important human functional neuroimaging modalities */highfield fMRI and high-resolution EEG-in an unusually specific and well-characterized neurophysiological setting.

The role of dopaminergic systems in the control of sexual behavior has been a subject of study for at least 40 years. Not surprisingly, reviews of the area have been published at variable intervals. However, the earlier reviews have been summaries of published research rather than a critical analysis of it. They have focused upon the conclusions presented in the original research papers rather than on evaluating the reliability and functional significance of the data reported to support these conclusions. During the last few years, important new knowledge concerning dopaminergic systems and their behavioral functions as well as the possible role of these systems in sexual behavior has been obtained. For the first time, it is now possible to integrate the data obtained in studies of sexual behavior into the wider context of general dopaminergic functions. To make this possible, we first present an analysis of the nature and organization of sexual behavior followed by a summary of current knowledge about the brain structures of crucial importance for this behavior. We then proceed with a description of the dopaminergic systems within or projecting to these structures. Whenever possible, we also try to include data on the electrophysiological actions of dopamine. Thereafter, we proceed with analyses of pharmacological data and release studies, both in males and in females. Consistently throughout this discussion, we make an effort to distinguish pharmacological effects on sexual behavior from a possible physiological role of dopamine. By pharmacological effects, we mean here drug-induced alterations in behavior that are not the result of the normal actions of synaptically released dopamine in the untreated animal. The conclusion of this endeavor is that pharmacological effects of dopaminergic drugs are variable in both males and females, independently of whether the drugs are administered systemically or intracerebrally. We conclude that the pharmacological data basically reinforce the notion that dopamine is important for motor functions and general arousal. These actions could, in fact, explain most of the effects seen on sexual behavior. Studies of dopamine release, in both males and females, have focused on the nucleus accumbens, a structure with at most a marginal importance for sexual behavior. Since accumbens dopamine release is associated with all kinds of events, aversive as well as appetitive, it can have no specific effect on sexual behavior but promotes arousal and activation of non-specific motor patterns. Preoptic and paraventricular nucleus release of dopamine may have some relationship to mechanisms of ejaculation or to the neuroendocrine consequences of sexual activity or they can be related to other autonomic processes associated with copulation. There is no compelling indication in existing experimental data that dopamine is of any particular importance for sexual motivation. There is experimental evidence showing that it is of no importance for sexual reward.

The human body evolved while living in direct electrical contact (electrically grounded) with the earth. The question that arises is: Does loss of electrical contact with the earth affect human physiology? This double-blind study was designed to address this question by measuring several electrophysiological parameters of the body. Subjects were assigned to an experimental group that was grounded to the earth after a 28-minute baseline recording. Grounding the body (earthing) was achieved by placing electrode patches on the soles of the feet and connecting them to a conductive cable that was attached to a metal rod planted in the earth. The total recording time was 56 minutes. The control group was not grounded but "sham grounded." Part 1 of this study presented results from measurements taken with clinical biofeedback equipment. This paper presents results obtained on Jing-Well points using the SSVP (Single Square Voltage Pulse) method. With the SSVP method we were able to corroborate results presented in our first paper with the biofeedback system. The SSVP method results are that grounding the body produces a reduction in tension (relaxation) of the internal organs and a reduction in inflammation. We also postulated that the body was developed to take advantage of the contact with the earth through the feet by developing a system of distribution of electrons through the kidney meridian at K11. The present findings are consistent with the results of our previous study which concluded that grounded subjects experienced a reduction in stress and a normalization of the functioning of the autonomic nervous system after earthing. 6

We have investigated the haematocrit dependence of the electrical parameters (relative permittivity and conductivity) of blood. The measuring set-up, composed of an impedancemeter (HP 4291A), an open-ended coaxial line and a temperature controlling set, was designed for dielectric measurements in the 1 MHz to 1 GHz frequency range. Measurements were performed on ex vivo animal (cow and sheep) blood at 37 • C. The two dielectric parameters appeared to be strongly dependent on the haematocrit. The permittivity versus frequency decreases then increases when the haematocrit decreases. The conductivity increases in the whole frequency range when the haematocrit decreases. Due to the lack of comparative data on the frequency range explored, we compare the dielectric profiles with those deduced from the Maxwell-Fricke theoretical model.

To figure out whether the main empirical question "Is our brain hardwired to believe in and produce God, or is our brain hardwired to perceive and experience God?" is answered, this paper presents systematic critical review of the positions, arguments and controversies of each side of the neuroscientific-theological debate and puts forward an integral view where the human is seen as a psychosomatic entity consisting of the multiple levels and dimensions of human existence (physical, biological, psychological, and spiritual reality), allowing consciousness/mind/spirit and brain/body/matter to be seen as different sides of the same phenomenon, neither reducible to each other. The emergence of a form of causation distinctive from physics where mental/conscious agency (a) is neither identical with nor reducible to brain processes and (b) does exert "downward" causal influence on brain plasticity and the various levels of brain functioning is discussed. This manuscript also discusses the role of cognitive processes in religious experience and outlines what can neuroscience offer for study of religious experience and what is the significance of this study for neuroscience, clinicians, theology and philosophy. A methodological shift from "explanation" to "description" of religious experience is suggested. This paper contributes to the ongoing discussion between theologians, cognitive psychologists and neuroscientists.

In the context of language processing, the N280 is an anterior negative event-related potential pro¢le associated with the lexical categorization of grammatical function words versus content words. Subsequent studies suggested that this e¡ect was related to word statistics including length and frequency in the lexicon.The current research tests the hypothesis that the N280 e¡ect is related to an index of grammatical complexity. We recorded event-related potentials during a sentence reading task. Comparing content versus function words revealed the classic N280. Within function words, we compared the relative pronouns 'qui' and 'que' (which are identical for length and frequency) that in French indicate a subsequent simple (subject^subject) and complex (subject^object) relative clause, respectively. A left anterior N280 e¡ect was observed only for 'que', supporting our hypothesis that the N280 re£ects grammatical complexity that can be confounded with lexical category and statistical properties. NeuroReport16:1435^1438

Previous experiments have demonstrated that auditory (AS) and/or somatosensory (SS) stimulation can increase the duration of REM sleep periods in rats, cats and humans. The objectives of this study were to determine whether repeated AS stimulation causes habituation to the stimulus and whether any additive effects could be obtained with the simultaneous application of AS and SS. Three experimental procedures were used in this study. In experiment 1, animals were recorded for 4 consecutive days with AS, followed by a post-stimulus session. In experiment 2, they were recorded for 24 hours with AS applied at each REM period, followed by a subsequent 24-hours-post-stimulus recording. In experiment 3, animals underwent AS, SS stimulation, or simultaneous application of both in a random fashion at each REM period. The results of all experiments confirm previous findings showing that auditory or somatosensory stimuli significantly increase REM sleep period duration. In addition, AS--applie...

The effect of ethylenediamine derivatives of tetrodotoxin (enTTXI and enTTXn) on frog skeletal muscle was studied both electrophysiologically and biochemically. Electrophysiological experiments with one of these molecules (enTTX~) showed that the concentrations needed to block the early phase of the inward sodium current (Ko.5 = 7 nM) are much lower than those needed to block the late phase of inward current or muscle contraction (K0. 5 = 40nM). Conversely, tubular Na + channels are more sensitive to enTTXn than are surface Na + channels.

We investigated the effect of 5-HT6 receptor subtype activation on glutamatergic transmission by means of whole-cell patch-clamp electrophysiological recordings from medium spiny neurons of the striatum and layer V pyramidal neurons of the prefrontal cortex. To this aim, we took advantage of a novel ligand, ST1936, showing nM affinity and agonist activity at the 5-HT6 receptor subtype. Our data show that 5-HT6 receptor activation by ST1936 reduces the frequency of spontaneous excitatory postsynaptic currents, with an IC50 of 1.3 mM. Moreover, 5-HT6 receptor activation also reduced the amplitude of spontaneous excitatory postsynaptic currents recorded from medium spiny neurons, suggesting a mechanism of action involving postsynaptic 5-HT6 receptors,as further confirmed by the paired-pulse analysis on evoked excitatory postsynaptic currents and by recordings of miniature glutamatergic events. The inhibitory effect of ST1936 on glutamatergic transmission was prevented by the selective 5-HT6 receptor antagonist SB258585 and mimicked by a different agonist, WAY-181187.

Lesioning or chronic deep brain stimulation (DBS) of the nucleus ventralis intermedius results in abolition of tremor in the contralateral limbs in Parkinson's disease (PD) and also in essential tremor. Recently, chronic DBS of the subthalamic nucleus has also proved to be very effective in reducing contralateral limb tremor in PD. These targets have been less effective in controlling the complex limb tremor often seen in multiple sclerosis (MS). Consequently, other targets have been sought in cases of MS with tremor. We describe a patient with MS with disabling proximal and distal involuntary arm movements in whom we were able to obtain sustained control of contralateral arm tremor and achieve functional improvement of the affected arm by chronic DBS of the region of the zona incerta. We also highlight the important role played by local field potentials recorded from the brain, with simultaneous recording of corresponding EMGs, in target localisation.

1. The electrophysiological actions of quinacainol were investigated on sodium (I Na ), transient outward (i to ) and sustained-outward plateau (i Ksus ) potassium currents in rat isolated cardiac myocytes using the whole-cell patch-clamp technique and compared with quinidine.

Atrial fibrillation (AF) is the most common cardiac arrhythmia requiring medical therapy, and present treatment modalities are inadequate. Over the past few years, we have learned a great deal about the phenomenon of electrical remodeling, by which rapid atrial activation leads to changes in atrial electrical properties that promote AF initiation and maintenance. This knowledge opens up the possibility that electrical remodeling may itself be a novel therapeutic target in AF. The present paper reviews what is known about the basic mechanisms of atrial electrical remodeling and then discusses the experimental and clinical evidence that remodeling can be prevented by drug therapy. Despite great potential value, the development of pharmacological interventions to prevent atrial electrical remodeling is still in its infancy.

BACKGROUND Electrophysiological studies in patients with atrial fibrillation demonstrated the presence of electrical conduction between superior and inferior left pulmonary veins (PVs) that makes electrical disconnection of individual PVs difficult. Anatomically, the prevalence, sizes, and locations of the interpulmonary connections have not been investigated systematically.

Objective: Sleep loss and sleep disruption are common in critically ill patients and may adversely affect clinical outcomes. Although polysomnography remains the most accurate and reliable way to measure sleep, it is costly and impractical for regular use in the intensive care unit. This study evaluates the accuracy of two other methods currently used for measuring sleep, actigraphy (monitoring of gross motor activity) and behavioural assessment by the bedside nurse, by comparing them to overnight polysomnography in critically ill patients. Design: Observational study with simultaneous polysomnography, actigraphy and behavioural assessment of sleep. Setting: Medical-surgical intensive care unit. Patients and participants: Twelve stable, critically ill, mechanically ventilated patients [68 (13) years, Glasgow coma scale 11 (0)]. Interventions: None. Measurements and results: Sleep was severely disrupted, reflected by decreased total sleep time and sleep efficiency, high frequency of arousals and awakenings and abnormal sleep architecture. Actigraphy overestimated total sleep time and sleep efficiency. The overall agreement between actigraphy and polysomnography was \65%. Nurse assessment underestimated the number of awakenings from sleep. Estimated total sleep time, sleep efficiency and number of awakenings by nurse assessment did not correlate with polysomnographic findings. Conclusions: Actigraphy and behavioural assessment by the bedside nurse are inaccurate and unreliable methods to monitor sleep in critically ill patients.

Streptozotocin-induced diabetes mellitus is known to cause a reduction of both conduction velocity and axon caliber in sciatic nerves and also a decrease in muscle fiber size. The present study investigates whether the distal parts of the peripheral nervous system, including extra-and intrafusal muscle fibers, are more severely affected than the proximal segments in the diabetic state. Proximal and distal sensory nerve conduction velocities were monitored during a period of 3 months in rats rendered diabetic by injection of streptozotocin. Segments of the sciatic and ventral coccygeal nerves, and of the biceps femoris and lumbrical muscles, were studied by light and electron microscopy, including morphometric analysis. In contrast to previous studies, daily suboptimal insulin injections were given to prevent acute metabolic complications. Sensory conduction velocity in the ventral coccygeal nerve was significantly ( P < 0.05) decreased in the diabetic rats compared to controls. Proximal and distal nerve segments were equally affected. Mean cross-sectional axon area of the sciatic nerve was moderately, but significantly (P < 0.05), smaller in insulin-treated diabetic rats than in controls. In both the sciatic nerve and the terminal, intrafusal nerve segments, occasional axons showed moderate dystrophic changes. Fibers of the intrafusal nerve segments appeared to be equally affected compared to the fibers in the sciatic nerve, although no quantitative comparison was made. The increase of small caliber skeletal muscle fibers in experimental streptozotocin-induced diabetes was confirmed. These findings indicate that proximal and distal segments of peripheral nerves are affected equally in the early stages of experimental diabetic neuropathy.

Orphenadrine has been used as an antiparkinsonian, antispastic and analgesic drug for many years. Here we show that orphenadrine inhibits [3H]MK-801 binding to the phencyclidine (PCP) binding site of the N-methyl-D-aspartate (NMDA)-receptor in homogenates of postmortem human frontal cortex with a Ki-value of 6.0 + 0.7 ~M. The NMDA receptor antagonistic effects of orphenadrine were assessed using concentration-and patch-clamp techniques on cultured superior colliculus neurones. Orphenadrine blocked open NMDA receptor channels with fast kinetics and in a strongly voltagedependent manner. The ICs0-value against steady state currents at-70mV was 16.2 _+ 1.6 ~tM (n = 6). Orphenadrine exhibited relatively fast, concentration-dependent open channel blocking kinetics (Kon 0.013 + 0.002 106M-1S-1) whereas the offset rate was concentration-independent (Kof f 0.230 _+ 0.004S-1). Calculation of the ratio Koff/Kon revealed an apparent Kd-value of 17.2 ~tM which is nearly identical to the ICs0 calculated at equilibrium.

öTo elucidate the role of dendritic morphology in signal transfer, the passive propagation of somatic and dendritic potentials was compared in multi-compartment models of three interneuron subpopulations in the CA1 region. Nine calbindin-, 15 calretinin-and 10 parvalbumin-containing cells were modelled incorporating the detailed geometry, the currents of the action potentials in the soma, and the AMPA, N-methyl-D-aspartate and GABA-B receptor-mediated postsynaptic currents in the dendrites. The cable properties show characteristic di¡erences among the subpopulations. The morphotonic length of calbindin and calretinin cell dendrites is larger than of parvalbumin cells. Thus parvalbumin cells are more compact than calbindin or calretinin cells unless the ratio of their axial and membrane resistivities exceeds the ratios of the other two cell types by more than 33%. In calbindin cells, the distal parts of the extremely long dendrites that invade the alveus are virtually isolated from the soma for passively propagating signals. The synaptic potentials evoked at a given morphotonic distance from the soma show larger di¡erences locally on the dendrites than on the soma in all subpopulations. Both the somatic and dendritic amplitude ratios are the smallest in PV cells. In calbindin cells the somatic amplitude of synaptic potentials evoked at the same morphotonic distance from the soma is similar regardless of the number of branchpoints along their path. In calretinin and parvalbumin cells, from dendrites with long primary segments synaptic potentials reach the soma with larger amplitude than from dendrites that are branching close to the soma. The dendrites with the larger impact on somatic membrane potential are usually the dendrites that enter the stratum lacunosum-moleculare. These results indicate that dendritic morphology plays a role in changing the e¡ectiveness of synaptic potentials evoked at di¡erent dendritic locations, and in this way is likely to be an important factor in determining the integrative properties of the di¡erent neuron populations.

Hy\VES, D.L. AND FURMAN, S.: Atrio-ventricular and ventriculo-atrial conduction times in patients undergoing pacemaker implant. Pacemaker mediated reentrant tachycardias have been seen frequently during use 0/ dual chamber sensing pacemakers and are dependent on the presence of intact retrograde (ventriculo-atrial] conduction. The status of a patient's retrograde (VA) conduction cannot be deferminedfrom fhe surface electrocardiogram. At the time of pacemaker implant the state of antegrade conduction should be determined at incremental atrial pacing rates, the exact timing measured from the intracardiac electrograms, i.e., from the intrinsic deflection of the atrium to the intrinsic deflection of the ventricle. With this information obtained in 53 patients, it was possible to determine which patients could safely receive dual chamber sensing pacemaker devices, the appropriate pacemaker atriai refractory period setting to avoid pacemaker mediated tachycardias in those patients with intuct retrograde conduction, and the optimal timing for programming the pacemaker's AV delay. Patients who have been studied in this manner and who were felt to be suitable for a dual chamber sensing device have not displayed pacemaker mediated reentrant tachycardias. Forty-seven percent of all patients who require pacemaker impiant have VA 1:1 conduction: 67% of those with sinus node dysfunction and lVA. of those with complete antegrade bJock have VA conduction at a mean interval of 235 ± 5d ms (range 110-380

Arrestins are members of a superfamily of proteins that arrest the activity of G-protein coupled receptors. Mouse cone photoreceptors express two visual arrestins, Arr1 and Arr4 (Carr). We quantified their expression levels and subcellular distributions in mouse cones: total Arr1 was estimated to be in an ~ 6:1 ratio to cone opsin, about 50-fold higher than Arr4. Recordings from single cones of Arr1 −/− and Arr4 −/− mice establish that both proteins are competent to arrest the activity of photoactivated S-and M-cone opsins. Recordings from Arr1 −/− , Arr4 −/− double-knockout mice establish a requirement for at least one of the two visual arrestins for normal cone opsin inactivation at all flash intensities. These recordings also reveal low activity photoproducts of S-and M-opsins that are absent when Grk1 and an arrestin are co-expressed, but which decay 70-fold more rapidly than the comparable photoproducts of rhodopsin in rods.

The dynamic clamp uses computer simulation to introduce artificial membrane or synaptic conductances into biological neurons and to create hybrid circuits of real and model neurons. In the ten years since it was first developed, the dynamic clamp has become a widely used tool for the study of neural systems at the cellular and circuit levels. This review describes recent state-ofthe-art implementations of the dynamic clamp and summarizes insights gained through its use, ranging from the role of voltage-dependent conductances in shaping neuronal activity to the effects of synaptic dynamics on network behavior and the impact of in vivo-like input on neuronal information processing.

One of the major limitations in the use of genetically modified mice for studying cognitive functions is the lack of regional and temporal control of gene function. To overcome these limitations, a forebrain-specific promoter was c o m b i n e d with the tetracycline transactivator system to achieve both regional and temporal control of transgene expression. Expression of an activated calcium-independent form of c a l c i u m -c a l m o d u l i n -d e p e ndent kinase II (CaMKII) resulted in a loss of h i p p o c a m p a l long-term potentiation in response to 10-hertz stimulation and a deficit in spatial memory, a form of explicit memory. Suppression of transgene expression reversed both the physiological and the memory deficit. When the transgene was expressed at high levels in the lateral amygdala and the striatum but not other forebrain structures, there was a deficit in fear conditioning, an implicit m e m o r y task, that also was reversible. Thus, the CaMKII signaling pathway is critical for both explicit and implicit m e m o r y storage, in a manner that is independent of its potential role in development.

A qualitative mathematical model is presented that examines membrane potential feedback on synthesis of inositol 1,4,5-trisphosphate (IP 3 ), and its role in generation and modulation of slow waves. Previous experimental studies indicate that slow waves show voltage dependence, and this is likely to result through membrane potential modulation of IP 3 . It is proposed that the observed response of the tissue to current pulse, pulse train, and maintained current injection can be explained by changes in IP 3 , modulated through a voltage-IP 3 feedback loop. Differences underlying the tissue responses to current injections of opposite polarities are shown to be due to the sequence of events following such currents. Results from this model are consistent with experimental findings and provide further understanding of these experimental observations. Specifically, we find that membrane potential can induce, abolish, and modulate slow wave frequency by altering the excitability of the tissue through the voltage-IP 3 feedback loop.

Six adults with non-insulin dependent diabetes mellitus participated in a laboratory procedure to determine the effects of an acute stressor, mental arithmetic, on blood glucose, cardiovascular, and subjective indices of stress. They then completed 12 days home monitoring of stressful events, subjective stress, and blood glucose. Diet and activity were controlled to evaluate the direct effects of stress on blood glucose in the natural environment. Laboratory results showed significant increases in blood glucose, cardiovascular (HR and SBP), and subjective stress ratings during the mental arithmetic task when compared to a resting condition. Home monitoring data were consistent with the laboratory findings; blood glucose range tended to be greater on high vs low stress days, especially when the difference between high and low stress was greatest. These findings suggest that the laboratory stress induction procedure was externally valid and that in the natural environment, stress has a hyperglycemic effect on blood glucose. INTRODUCITON Diabetes mellitus has ranked among the ten leading causes of death since 1932, and is associated with increased risk for new blindness, renal failure, and cardiovascular and peripheral vascular disease (Kovar, Harris; & Hadden, 1987). Although the biochemical mechanisms responsible for such complications are not entirely clear, it is generally believed that they result from chronic hyperglycemia (high blood glucose levels), and that they can be prevented or delayed if adequate control of blood glucose levels is achieved and maintained (Pohl, Gonder-Frederick & Cox, 1984). Factors that disrupt diabetic control are, thus, a major concern for individuals with diabetes. In the present study, we investigated the effects of psychological stress on blood glucose control among adults with Type II (non-insulin dependent) diabetes mellitus. Data from varied sources support the hypothesis that stress disrupts diabetic control and causes hyperglycemia. Animal models, for example, have implicated stress in the development of Type I (insulin dependent) diabetes (Carter, Hemnan, Stokes & Cox. 1987). and in causina a hvneralvcemic resuonse in Type II diabetes (Surwit, Feinglos, Livingston, Kuhn & McCubbin,' 1984): Epinephrine infusion s&dies also support the-hypothesis that stress disrupts metabolic processes leading to hyperglycemic episodes (Gerich, Lorenxi, Tzalikian & Karam, 1976). Finally, studies measuring naturally-occurring life strcssors have shown that higher levels of stressful events are reported among newly diagnosed diabetics vs nondiabetic controls (Robinson & Fuller, 1985). and among poorly-vs well-controlled diabetic patients (Schwartz, Springer, Flaherty UC Kiani, 1986). It is theorized that such stress effects occur via enhanced sympathetic nervous system and neuroendocrine activity

Animals have evolved several chemosensory systems for detecting potentially dangerous foods in the environment. Activation of specific sensory cells within these chemosensory systems usually elicits an aversive behavioral response, leading to avoidance of the noxious foods. Blowflies respond to sugars, salts and water through the activation of specific chemoreceptor neurons in the antennal, labellar and tarsal chemosensillae. These insects also detect deterrent stimuli with the so called fifth or deterrent cell. Using forensically important flies (blowflies) as a model organism, the question was if these flies have the ability to detect the nutritional value of corpses when injected with different doses of morphine. In the attempt to gain information on the mechanisms underlying reception of noxious and repellent compounds, electrophysiological and behavioral experiments have been performed to confirm the hypothesis that morphine sulfate has a repellent effect on fly attraction to c...

Our earlier studies demonstrated that representative microbial substances--lipopolysaccharide, peptidoglycan, and poly-inosine: poly-cytosine (poly(I):(C))--increased the spontaneous discharge rates and sensory-evoked responses of isolated locus coeruleus (LC) neurons in a dose- and time-related manner after i.p. injection into rats. We then turned our attention to the mechanism by which microbial substances administered into the peritoneal cavity affect the LC neurons. The involvement of the subdiaphragmatic vagus nerves was examined in this regard since several brain responses to peripherally administered lipopolysaccharide have been found to depend upon the integrity of these nerves. The experiments reported here show that lipopolysaccharide, peptidoglycan, and poly(I):(C) all failed to excite LC neurons after i.p. injection into rats that had previously been subjected to complete transection of the subdiaphragmatic vagus nerves. Furthermore, selective transection of the subdiaph...

Surface electromyographic (EMG) amplitude and mean power frequency (MPF) were used to study the isometric muscular activity of the right versus the left upper trapezius muscles in 14 healthy right-handed women. The EMG activity was recorded simultaneously with force signals during a 10-15 s gradually increasing exertion of force, up to maximal force. Only one side at a time was tested. On both sides there was a significant increase in EMG amplitude (~tV) during the gradually increasing force from 0% to 100% maximal voluntary contraction (MVC). The right trapezius muscle showed significantly less steep slopes for regression of EMG amplitude versus force at low force levels (0%-40% MVC) compared intra-individually with l)igh force levels (60%-100% MVC). This was not found for the left trapezius muscle. At 40% MVC a significantly lower MPF value was found for the right trapezius muscle intra-individually compared with the left. An increase in MPF between 5% and 40% MVC was statistically significant when both sides were included in the test. The differences in EMG activity between the two sides at low force levels could be due to more slow-twitch (type I fibres) motor unit activity in the right trapezius muscles. It is suggested that this is related to right-handed activity.

The influence of CCK-A receptor antagonism on pancreatic exocrine secretion and duodenal EMG, and the mechanism(s) involved in CCK-induced pancreatic secretion were studied in conscious calves. Seven 1-week-old calves were fitted with a pancreatic duct catheter, duodenal cannula and duodenal electrodes. Pancreatic exocrine secretion and duodenal EMG were studied following intraduodenal CCK-A receptor antagonist (Tarazepide), intravenous atropine, and intravenous or intraduodenal CCK-8 administrations. Tarazepide decreased duodenal electric activity, reduced interdigestive pancreatic secretion, especially protein; reduced cephalic and early postprandial (milk) induced secretion of bicarbonate and protein. Pancreatic protein secretion to intravenous CCK-8 was little affected by atropine, but was significantly reduced by Tarazepide+/-atropine; in contrast, protein secretion to intraduodenal CCK-8 was abolished by Tarazepide or atropine. We conclude that pre- and especially early postpr...

Words from different classes have been found to activate different brain areas. However, it is unclear whether grammatical word properties, for example their being part of different lexical categories (e.g. nouns vs. verbs) or semantic features of the words (e.g. that they refer to visually perceived entities or to actions) are relevant for eliciting differential brain responses. We tested this by comparing brain potentials elicited by nouns and verbs that varied in their action and visual associations. Naturally spoken word stimuli were from three categories: (1) nouns with strong visual associations;

In spite of the detailed anatomical knowledge available, the functional significance of the cerebellar wiring diagram is still obscure. Since there arc no variations in the anatomy throughout the whole cortical plane, it is plausible to assume that the basic operation is the same in all parts of the cerebellum. The 'wiring' suggests that local activity must depend on the spatio-temporal organization of the inputs. Neocortical input reaches the cerebellar cortex from nearly all cortical areas via mossy fibers terminating on the granular cells. We simulated such an input to the granular layer in acute slices of rat cerebellar cortex using an array of II stimulating electrodes. By successively switching the stimulus current from one electrode to the next, a 'moving' input to the granular layer is simulated. Our experiments show that the cerebellar cortex is specifically activated by 'moving' stimuli applied to the granular layer. The activation is a function of 'movement' direction and velocity. Thus, it enables the cerebellar cortex to act as a movement detector. Such behavior has previously been postulated on anatomical grounds [Braitenberg,

Novel stimuli in all sensory modalities are highly effective in attracting and focusing attention. Stimulus-specific adaptation (SSA) and brain activity evoked by novel stimuli have been studied using population measures such as imaging and event-related potentials, but there have been few studies at the single-neuron level. In this study we compare SSA across different populations of neurons in the inferior colliculus (IC) of the rat and show that a subclass of neurons with rapid and pronounced SSA respond selectively to novel sounds. These neurons, located in the dorsal and external cortex of the IC, fail to respond to multiple repetitions of a sound but briefly recover their excitability when some stimulus parameter is changed. The finding of neurons that respond selectively to novel stimuli in the mammalian auditory midbrain suggests that they may contribute to a rapid subcortical pathway for directing attention and ⁄ or orienting responses to novel sounds.

EMG responses elicited by sudden onset of free fall and a startling auditory stimulus were investigated in healthy subjects while lying on a couch with their eyes closed. Muscle responses were recorded from masseter (V cranial nerve), orbicularis oculi and mentalis (VII nerve) and sternomastoid and trapezoid (XI nerve). A similar sequence of muscle activation and absolute latencies occurred in response to both stimulus modalities, consisting of a blink (30 msec) followed simultaneously by mentalis, sternomastoid and trapezoid (55 msec). Masseter could either be simultaneously activated with the latter muscles or follow after a delay of 10-20 msec. A patient with bilateral cochleo-vestibular nerve section had responses at comparable latencies in the free fall experiment. The similarities between the reaction to free fall and a startling auditory stimulus indicate that the early response to free fall constitutes a startle and that various stimuli converge onto a common response genera...

The timecourse and scalp topography of interactions between neural responses to stimuli in different visual quadrants, straddling either the vertical or horizontal meridian, were studied in 15 subjects. Visual evoked potentials (VEPs) were recorded from 64 electrodes during a simple reaction time (RT) task. VEPs to single stimuli displayed in different quadrants were summed ('sum') and compared to the VEP response from simultaneous stimulation of the same two quadrants ('pair'). These responses would be equivalent if the neural responses to the single stimuli were independent. Divergence between the 'pair' and 'sum' VEPs indicates a neural response interaction. In each visual field, interactions occurred within 72 -86 ms post-stimulus over parieto-occipital brain regions. Independent of visual quadrant, RTs were faster for stimulus pairs than single stimuli. This replicates the redundant target effect (RTE) observed for bilateral stimulus pairs and generalizes the RTE to unilateral stimulus pairs. Using Miller's 'race' model inequality (Miller J. Divided attention: evidence for coactivation with redundant signals, Cognitive Psychology 1982;14:247-79), we found that probability summation could fully account for the RTE in each visual field. Although measurements from voltage waveforms replicated the observation of earlier peak P1 latencies for the 'pair' versus 'sum' comparison (Miniussi C, Girelli M, Marzi CA. Neural site of the redundant target effect: electrophysiological evidence. Journal of Cognitive Neuroscience 1998;10:216-30), this did not hold with measurements taken from second derivative (scalp current density) waveforms. Since interaction effects for bilateral stimulus pairs occurred within 86 ms and require interhemispheric transfer, transcallosal volleys must arrive within 86 ms, which is earlier than previously calculated. Interaction effects for bilateral conditions were delayed by :10 ms versus unilateral conditions, consistent with current estimates of interhemispheric transmission time. Interaction effects place an upper limit on the time required for neuronal ensembles to combine inputs from different quadrants of visual space ( : 72 ms for unilateral and : 82 ms for bilateral conditions).

In order to set up a non-invasive, reliable and reproducible model for investigating a-motoneuronal activity, we studied the electrophysiological features of a monosynaptic H-reflex in anaesthetised intact rats, anaesthetised and non-anaesthetised rats transected at Ž . the level of the obex. Electrical stimulation of the tibial nerve at the ankle elicited an H-reflex, an F-wave and a direct motor M response in the plantaris muscles of all preparations. The H-reflex and F-wave exhibited very similar latencies. The H-reflex had a low threshold and a constant latency. Its amplitude increased as a function of stimulus intensity to reach a maximum value but then decreased when the stimulus intensity was further increased. It could follow high rates of stimulation without any change in shape or latency. The F-wave had a lower amplitude which together with its latency varied from one stimulus to the next. It appeared with intensities of stimulation that elicited an almost maximal M-response and did not decrease when the stimulation was increased. It did not appear systematically from one stimulus to the next. The H-reflex, but neither the F-wave nor the direct motor M-response, was depressed both by vibratory stimuli applied on the Achilles' tendon and following nociceptive stimulation of the flexor reflex afferents. This model could be used for assessing any potential direct effect on motoneurones of a physiological or pharmacological conditioning procedure. q 1998 Elsevier Science B.V.

# Springer-Verlag 2005 of cystic fibrosis transmembrane regulator, KCNQ1, and CLCA1 mRNAs were not found to be different between the two segments. Conclusion: There was a clear segmental heterogeneity with regard to electrogenic secretion in the human colon, and this difference can be explained by differences in the ascending colon and rectum.

We previously reported that low Mg 2+ or 4-aminopyridine induced seizure-like events in organotypic hippocampal slice cultures (OHSCs) were resistant to standard antiepileptic drugs . We now show that high-frequency electrical stimulation induced ictal-like afterdischarges in OHSCs are effectively suppressed by the standard antiepileptic drugs phenytoin and carbamazepine. Thus, a single OHSC can express both pharmacoresistant and pharmacosensitive epileptiform activities.

We have studied the ability of nonionic detergents and hydrophilic polymers to seal permeabilized membranes of damaged cells, rescuing them from progressive dissolution, degeneration, and death. We report that a single subcutaneous injection of the tri-block copolymer, Poloxamer 188 (P188) 6 hr after a severe compression of the adult guinea pig spinal cord is able to: (1) preserve the anatomic integrity of the cord; (2) produce a rapid recovery of nerve impulse conduction through the lesion; and (3) produce a behavioral recovery of a spinal cord dependent long tract spinal cord reflex. These observations stood out against a control group in blinded evaluation. Conduction through the lesion was monitored by stimulating the tibial nerve of the hind limb, and measuring the arrival of evoked potentials at the contralateral sensory cortex of the brain (somatosensory evoked potentials; SSEP). Behavioral recovery was determined by a return of sensitivity of formerly areflexic receptive fields of the cutaneous trunchi muscle (CTM) reflex. This contraction of back skin in response to tactile stimulation is totally dependent on the integrity of an identified bilateral column of ascending long tract axons. A statistically significant recovery of both SSEP conduction through the lesion and the CTM reflex occurred in P188-treated animals compared to vehicle-treated controls. Quantitative 3D computer reconstruction of the lesioned vertebral segment of spinal cord revealed a statistically significant sparing of spinal cord parenchyma and a significant reduction in cavitation of the spinal cord compared to control animals We determined that the proportion of P188-treated animals that recovered evoked potentials were nearly identical to that produced by a subcutaneous injection of polyethylene glycol (PEG). In contrast, P188 was not as effective as PEG in producing a recovery of CTM functioning. We discuss the likely differences in the mechanisms of action of these two polymers, and the possibilities inherent in a combined treatment.

 The purpose of this study was to provide objective information on the involvement of different abdominal and hip flexor muscles during various types of common training exercises used in rehabilitation and sport. Six healthy male subjects performed altogether 38 different static and dynamic training exercises – trunk and hip flexion sit-ups, with various combinations of leg position and support, and bi- and unilateral leg lifts. Myoelectric activity was recorded with surface electrodes from the rectus abdominis, obliquus externus, obliquus internus, rectus femoris, and sartorius muscles and with indwelling fine-wire electrodes from the iliacus muscle. The mean electromyogram amplitude, normalised to the highest observed value, was compared between static and dynamic exercises separately. The hip flexors were highly activated only in exercises involving hip flexion, either lifting the whole upper body or the legs. In contrast, the abdominal muscles showed marked activation both during trunk and hip flexion sit-ups. In hip flexion sit-ups, flexed and supported legs increased hip flexor activation, whereas such modifications did not generally alter the activation level of the abdominals. Bilateral, but not unilateral, leg lifts required activation of abdominal muscles. In trunk flexion sit-ups an increased activation of the abdominal muscles was observed with increased flexion angle, whereas the opposite was true for hip flexion sit-ups. Bilateral leg lifts resulted in higher activity levels than hip flexion sit-ups for the iliacus and sartorius muscles, while the opposite was true for rectus femoris muscles. These data could serve as a basis for improving the design and specificity of test and training exercises.

Normal maturation and functioning of the central auditory system affects the development of speech perception and oral language capabilities. This study examined maturation of central auditory pathways as reflected by age-related changes in the P1/N1 components of the auditory evoked potential (AEP). A synthesized consonant-vowel syllable (ba) was used to elicit cortical AEPs in 86 normal children ranging in age from 6 to 15 years and ten normal adults. Distinct age-related changes were observed in the morphology of the AEP waveform. The adult response consists of a prominent negativity (N1) at about 100 ms, preceded by a smaller P1 component at about 50 ms. In contrast, the child response is characterized by a large P1 response at about 100 ms. This wave decreases significantly in latency and amplitude up to about 20 years of age. In children, P1 is followed by a broad negativity at about 200 ms which we term N1b. Many subjects (especially older children) also show an earlier negativity (N1a). Both N1a and N1b latencies decrease significantly with age. Amplitudes of N1a and N1b do not show significant age-related changes. All children have the N1b; however, the frequency of occurrence of N1a increases with age. Data indicate that the child P1 develops systematically into the adult response; however, the relationship of N1a and N1b to the adult N1 is unclear. These results indicate that maturational changes in the central auditory system are complex and extend well into the second decade of life.