Estimation of Coupling Strength in Regenerated Lamprey Spinal Cords Based on a Stochastic Phase Model

We present a simple stochastic model of two coupled phase oscillators and a method of fitting the model to experimental spike-train data or to sequences of burst times. We apply the method to data from lesioned isolated lamprey spinal cords. The remaining tracts at the lesion site are either regenerated medial tracts, regenerated lateral tracts, control medial tracts, or control lateral tracts. We show that regenerated tracts on average provide significantly weaker coupling than control tracts. We compare our model-dependent estimate of coupling strength to a measure of coordination based on the size of deflections in the spike-train cross-correlation histogram (CCH). Using simulated data, we show that our estimates are able to detect changes in coupling strength that do not change the size of deflections in the CCH. Our estimates are also more resistant to changes in the level of dynamic noise and to changes in relative oscillator frequency than is the CCH. In simulations with high levels of dynamic noise and in one experimental preparation, we are able detect significant coupling strength although there are no significant deflections in the CCH.     

Prolonged Decay of Evoked Inhibitory Postsynaptic Currents in Hippocampal Neurons Is Not Shaped by Asynchronous Release

During evoked release, several quanta of neurotransmitter are synchronously released in several GABA-ergic synapses. Assuming that not more than one vesicle is released at each release site, the decay of miniature and evoked IPSC (mIPSC and eIPSC, respectively) should coincide. In this study, we found that in a considerable part of the cultured hippocampal neurons eIPSC decayed more slowly than mIPSC did. We investigated the mechanisms underlying this difference using conventional electrophysiological approaches, deconvolution, simulations, and nonstationary noise analysis. Our results indicate that asynchronous release of synaptic vesicles cannot explain the prolonged decay of the GABA-ergic IPSC. We suggest that some interaction between the quanta at the pre- and/or post-synaptic level should result in a slower decay of the eIPSC in comparison with that of mIPSC.     

A Model of a Segmental Oscillator in the Leech Heartbeat Neuronal Network

We modeled a segmental oscillator of the timing network that paces the heartbeat of the leech. This model represents a network of six heart interneurons that comprise the basic rhythm-generating network within a single ganglion. This model builds on a previous two cell model (Nadim et al., 1995) by incorporating modifications of intrinsic and synaptic currents based on the results of a realistic waveform voltage-clamp study (Olsen and Calabrese, 1996). Due to these modifications, the new model behaves more similarly to the biological system than the previous model. For example, the slow-wave oscillation of membrane potential that underlies bursting is similar in form and amplitude to that of the biological system. Furthermore, the new model with its expanded architecture demonstrates how coordinating interneurons contribute to the oscillations within a single ganglion, in addition to their role of intersegmental coordination.     

Modulation of swimming speed in the pteropod mollusc,Clione limacina: Role of a compartmental serotonergic system

In locomotory systems, the central pattern generator and motoneuron output must be modulated in order to achieve variability in locomotory speed, particularly when speed changes are important components of different behavior acts. The swimming system of the pteropod molluscClione limacina is an excellent model system for investigating such modulation. In particular, a system of central serotonergic neurons has been shown to be intimately involved in regulating output of the locomotory pattern generator and motor system ofClione. There are approximately 27 pairs of serotonin-immunoreactive neurons in the central nervous system ofClione, with about 75% of these identified. The majority of these identified immunoreactive neurons are involved in various aspects of locomotory speed modulation. A symmetrical cluster of pedal serotonergic neurons serves to increase wing contractility without affecting wing-beat frequency or motoneuron activity. Two clusters of cerebral cells produce widespread responses that lead to an increase in pattern generator cycle frequency, recruitment of swim motoneurons, activation of the pedal serotonergic neurons and excitation of the heart excitor neuron. A pair of ventral cerebral neurons provides weak excitatory inputs to the swimming system, and strongly inhibits neurons of the competing whole-body withdrawal network. Overall, the serotonergic system inClione is compartmentalized so that each subsystem (usually neuron cluster) can act independently or in concert to produce variability in locomotory speed.     

Estimating the Strength and Direction of Functional Coupling in the Lamprey Spinal Cord

A method of estimating coupling strength between two neural oscillators based on their spikes trains (Kiemel and Cohen, J. Comput. Neurosci. 5: 267–284, 1998) is tested using simulated data and then applied to experimental data from the central pattern generator (CPG) for swimming in the lamprey. The method is tested using a model of two connectionist oscillators and a model of two endogenously bursting cells. For both models, the method provides useful estimates of the relative strength of coupling in each direction, as well as estimates of total strength. The method is applied to pairs of motor-nerve recordings from isolated 50-segment pieces of spinal cords from adult silver lampreys (Ichthyomyzon unicuspus). The strength and direction of coupling is estimated under control conditions and conditions in which intersegmental coupling between the two recording locations is weakened by hemisections of the spinal cords and/or chambers containing an inhibitory solution that blocks firing in postsynaptic cells. The relevance of these measures in constraining models of the CPG is discussed.     

Localized Bumps of Activity Sustained by Inhibition in a Two-Layer Thalamic Network

Based on head direction experiments in rats, the existence of localized bumps of thalamic activity has been proposed. We computationally demonstrate the existence of a novel class of localized bump solutions in a two-layer conductance-based thalamic network and analyze the mechanisms behind these stable patterns. In contrast to previous models of bump activity, here inhibition plays a crucial role in initially spreading neuronal firing and in subsequently sustaining it. In our model, we incorporate local strong, fast GABA(A) inhibition and diffuse weak, slow GABA(B) inhibition, based on previous biophysical experiments. These forms of inhibition contribute in different, yet complementary, ways to the observed pattern formation.     

Oscillatory Mechanisms in Pairs of Neurons Connected with Fast Inhibitory Synapses

We study dynamical mechanisms underlying oscillatory behavior in reciprocal inhibitory pairs of neurons, using a two-dimensionalcell model. We introduce one-and-two dimensional phase portraits to illustratethe behaviors, thus reducing the study of dynamical mechanisms to planar geometrical properties. We examined whether other mechanisms besides the escape and release mechanisms (Wang and Rinzel, 1992) might be needed for some cases of reciprocal inhibition, and show that, within the confines of a simple two-dimensional cell model, escape and releaseare sufficient for all cases. We divided the behaviors of a singlecell into six different types and examined the joint behaviors arising from every combination of pairs of cells with behaviors drawn from thesesix types. For the case of two quiescent cells or two cells eachhaving plateau potentials, bifurcation diagrams demonstrate therelations between synaptic threshold and synaptic strength necessaryfor oscillations by escape, oscillations by release, ornetwork-generated plateau potentials. Thus we clarify therelationship between plateau potentials and oscillations in a cell.Using the two dimensional cell model we examine 1:N beating betweencells and find that our simple model displays many of the essentialdynamical properties displayed by more sophisticated models, some ofwhich relate to thalamocortical spindling.     

Effect of Latrotoxin-Like Protein on Spontaneous Postsynaptic Activity in Hippocampal Cell Cultures

-Latrotoxin, an active component of black widow spider venom, is known to enhance spontaneous neurotransmitter release. In cultured rat hippocampal neurons, we studied the effects of latrotoxin-like protein (protein purified from the bovine brain and exhibiting some functional properties similar to those of -latrotoxin) on spontaneous GABA-ergic inhibitory currents (IPSC). Latrotoxin-like protein was found to dramatically increase the frequency of spontaneous IPSC recorded in cell cultures of dissociated hippocampal neurons in the presence of tetrodotoxin. Possible mechanisms of the action of latrotoxin-like protein on transmitter release are discussed.     

Coordinated motor activity in simulated spinal networks emerges from simple biologically plausible rules of connectivity

The spinal motor circuits of the Xenopus embryo have been simulated in a 400-neuron network. To explore the consequences of differing patterns of synaptic connectivity within the network for the generation of the motor rhythm, a system of biologically plausible rules was devised to control synapse formation by three parameters. Each neuron had an intrinsic probability of synapse formation (P _soma , specified by a space constant ) that was a monotonically decreasing function of its soma location in the rostro-caudal axis of the simulated network. The neurons had rostral and caudal going axons of specified length (L _axon ) associated with a probability of synapse formation (P _axon ). The final probability of synapse formation was the product of P _soma and P _axon . Realistic coordinated activity only occurred when L _axon and the probabilities of interconnection were sufficiently high. Increasing the values of the three network parameters reduced the burst duration, cycle period, and rostro-caudal delay and increased the reliability with which the network functioned as measured by the coefficient of variance of these parameters. Whereas both L _axon and P _axon had powerful and consistent effects on network output, the effects of on burst duration and rostro-caudal delay were more variable and depended on the values of the other two parameters. This network model can reproduce the rostro-caudal coordination of swimming without using coupled oscillator theory. The changes in network connectivity and resulting changes in activity explored by the model mimic the development of the motor pattern for swimming in the real embryo.     

诱导成年大鼠海马CA1区长时程压抑的强直刺激型式

标准低频率连续刺激(1～2 Hz,15 min)能够诱导幼年大鼠(＜4周)海马CA1区同突触长时程压抑(long-term depression,LTD),而只有较高频率且持续时间较长的连续刺激才能诱导出成年动物该部位稳定的LTD.本研究采用成年大鼠海马脑片标本,电刺激Schaffer侧枝传入纤维,在CA1区锥体细胞层记录群体锋电位,选用两种新的刺激参数以观测不同刺激型式在诱导成年大鼠LTD中的作用.诱导LTD的刺激参数为(1)2 Hz,5串,串长60 s,串间隔60 s;(2)5 Hz,5串,串长24 s,串间隔96 s;(3)对照组参数2 Hz,300 s.结果显示,对照参数未能诱导出LTD;而两种频率不同但脉冲总数与刺激总时程相同的多串刺激,即参数(1)与参数(2),均在成年大鼠海马CA1区诱导产生了LTD.两种参数所诱导的LTD特征具有参数特异性,该特征主要表现为LTD诱导潜伏期和LTD的幅度参数(1)、(2)诱导的LTD的潜伏期分别为15～25 min和30～40 min;强直刺激后80 min时LTD的幅度分别为(57.5±2.8)%和(67.7±3.4)%.以上结果表明特定型式的低频率刺激能够诱导成年大鼠海马CA1区的LTD,提示LTD的诱导与刺激的组合型式相关,并且2 Hz较5 Hz的多串刺激在诱导LTD中更为有效.     

Phase Maintenance in the Pyloric Pattern of the Lobster (Panulirus interruptus) Stomatogastric Ganglion

The extent to which individual neural networks can producephase-constant motor patterns as cycle frequency is altered has notbeen studied extensively. I investigated this issue in thewell-defined, rhythmic pyloric neural network. When pyloric cyclefrequency is altered three- to fivefold, pyloric inter-neuronaldelays shift by hundreds to thousands of msec, and all pyloricpattern elements show strong phase maintenance. The experimentalparadigm used is unlikely to activate exogenous inputs to thenetwork, and these delay changes are thus likely to arise fromphase-compensatory mechanisms intrinsic to the network. Pyloricinter-neuronal delays depend on the time constants of the networkssynapses and of the membrane properties of its neurons. The observeddelay shifts thus suggest that, in response to changes in overallcycle frequency, these constants vary so as to maintain patternphasing.     

相连四组神经的传入对在体肠系膜下神经节细胞兴奋的作用

运用在体细胞内电位记录法,观察了与肠系膜下神经节（IMG）相连的四组神经对IMG神经元自发电位活动的影响,结果显示扩和结肠或膀胱时,IMG细胞自发电位活动增加;切断或阻滞任一组神经均使IMG细胞电位活动受抑。其中结肠神经和腹下神经分别传导源自结肠尾段和膀胱等盆腔脏器的外周性兴奋,节间神经同时传导源自脊髓的中枢性和结肠的外周笥兴奋,肠系膜下神经节细胞的兴奋不仅源自脊髓,而且来源于结肠和膀胱。定量研究表明后者比前者对神经节细胞兴奋的影响更大。     

Modelling inter-segmental coordination of neuronal oscillators: synaptic mechanisms for uni-directional coupling during swimming in Xenopus tadpoles

Locomotion requires longitudinal co-ordination. We have examined uni-directional synaptic coupling processes between two classes of neuronal network oscillators: autonomously active intrinsic oscillators, and potential oscillators that lack sufficient excitatory drive for autonomous activity. We model such oscillator networks in the bilaterally-symmetrical, Xenopus tadpole spinal cord circuits that co-ordinate swimming. Glutamate coupling EPSPs can entrain a second oscillator of lower frequency provided their strength is sufficient. Fast (AMPA) EPSPs advance spiking on each cycle, while slow (NMDA) EPSPs increase frequency over many cycles. EPSPs can also enable rhythmicity in potential oscillators and entrain them. IPSPs operate primarily on a cycle-by-cycle basis. They can advance or delay spiking to entrain a second intrinsic oscillator with higher, equal or lower frequency. Bilaterally symmetrical coupling connections operate twice per cycle: once in each half-cycle, on each side of the receiving oscillator. Excitatory and inhibitory coupling allow entrainment in complimentary areas of parameter space.     

The brain can eat: Establishing the existence of a central pattern generator for feeding in third instar larvae of Drosophila virilis and Drosophila melanogaster

To establish the existence of a central pattern generator for feeding in the larval central nervous system of two Drosophila species, the gross anatomy of feeding related muscles and their innervation is described, the motor units of the muscles identified and rhythmic motor output recorded from the isolated CNS. The cibarial dilator muscles that mediate food ingestion are innervated by the frontal nerve. Their motor pathway projects from the brain through the antennal nerves, the frontal connectives and the frontal nerve junction. The mouth hook elevator and depressor system is innervated by side branches of the maxillary nerve. The motor units of the two muscle groups differ in amplitude: the elevator is always activated by a small unit, the depressor by a large one. The dorsal protractors span the cephalopharyngeal skeleton and the body wall hence mediating an extension of the CPS. These muscles are innervated by the prothoracic accessory nerve. Rhythmic motor output produced by the isolated central nervous system can simultaneously be recorded from all three nerves. The temporal pattern of the identified motor units resembles the sequence of muscle contractions deduced from natural feeding behavior and is therefore considered as fictive feeding. Phase diagrams show an almost identical fictive feeding pattern is in both species.     

Interneuronal mechanisms for learning-induced switch in a sensory response that anticipates changes in behavioral outcomes

1. Download : Download high-res image (261KB)
2. Download : Download full-size image

     

Physical Activity as a Predictor of Weight Maintenance in Previously Obese Subjects

We examined the association between exercise and weight loss maintenance in a group of 45 previously obese subjects 2 years post very-low-calorie diet (VLCD) to suggest exercise goals for this population. At baseline, subjects weighed a mean 100 kg and had a mean total cholesterol (TC) of 5.8 mmol/L. With VLCD they lost an average 28 kg and decreased their TC by 1.6 mmol/L. Two years post-VLCD their weight and lipids were measured and they completed a physical activity survey (Paffenbarger). Subjects were grouped into tertiles by reported exercise levels: low active (< 850 kcals per week), moderate active (850–1575 kcals per week) and high active (> 1575 kcals per week). Walking accounted for the greatest calorie expenditure (65%). Analysis of variance showed that baseline characteristics and weight and blood lipid changes during the VLCD did not differ (P>0.05) among groups. At follow-up, high active patients maintained significantly greater weight loss, had a lower percent regain and a significantly greater decrease in total cholesterol (P < 0.05) than less active patients. Multiple regression analysis indicated that total exercise calories independently predicted overall weight loss and percent regain (r = 0.66 and r = 0.62, respectively). Exercise calories also predicted total cholesterol change (r=-0.37). The high active group walked more miles (16.2 per week) than the low and moderate active groups (4.8 and 9.1 per week, respectively) and exercised more days per week (5.3 vs. 1.9 and 3.7). The low and moderate active groups regained virtually equal amounts of weight, even though the moderate group expended twice as many kcals per week as the low active group. These data demonstrate that increased exercise levels enhance weight loss maintenance.     

Oscillations in a Simple Neuromechanical System: Underlying Mechanisms

A half-center neural oscillator was coupled to a simple mechanical system to study the closed-loop interactions between a central pattern generator and its effector muscles. After a review of the open-loop mechanisms that were previously introduced by Skinner et al. (1994), we extend their geometric approach and introduce four additional closed-loop mechanisms by the inclusion of an antagonistic muscle pair acting on a mass and connected to the half-center neural oscillator ipsilaterally. Two of the closed-loop mechanisms, mechanical release mechanisms, have close resemblance to open-loop release mechanisms whereas the latter two, afferent mechanisms, have a strong dependence on the mechanical properties of the system. The results also show that stable oscillations can emerge in the presence of sensory feedback even if the neural system is not oscillatory. Finally, the feasibility of the closed-loop mechanisms was shown by weakening the idealized assumptions of the synaptic and the feedback connections as well as the rapidity of the oscillations.     

Neural organization of the ventilatory activity in the frog,Rana catesbeiana. II

The paralyzed, decerebrate frog, Rana catesbeiana, displays “fictive” oropharyngeal and pulmonary ventilations. In order to evaluate the neuronal correlates of these two centrally programmed ventilatory bursting patterns, we have performed intra-and extracellular recordings of bulbar respiratory neurons in this fictively breathing preparation. A total of 123 respiratory neurons were recorded from the caudal medulla. Of 51 antidromically activated neurons, 20 were vagal motoneurons and 31 were hypoglossal motoneurons. Respiratory neurons that depolarized during the lung (L) or non-lung (N) ventilatory phases were classified as L or N neurons, respectively. Phase spanning neurons (S) were active during both L and N phases. Some neurons showed oscillations of membrane potential synchronous with oropharyngeal ventilation. Those active during the buccal elevation phase were exclusively L neurons whereas those having buccal depressor activity were exclusively N neurons. Synaptic drive potentials were observed in all neurons recorded intracellularly. In some neurons, hyperpolarization was caused by inhibitory postsynaptic potentials, as demonstrated by reversal of membrane potential trajectory after intracellular chloride iontophoresis. Some individual motoneurons and interneurons exhibited both pulmonary and buccal ventilatory activity, indicating that both pattern generators project to a common motor control system. 1994 John Wiley & Sons, Inc.