The neural basis of catalepsy in the stick insect cuniculina impigra

Intracellular records from somata of FETi and SETi were performed during sinusoidal and rampwise stimulation of the femoral chordotonal organ. The responses were larger on average in SETi but this could be random. All other parameters (form of amplitude-frequency plot, phase-frequency plot, half-lives of rise and fall during ramp-wise stimulations) were not significantly different for both neurons. The responses of both neurons are symmetrical for stretch and release stimuli. Thus, these motor neurons are the decisive rectifiers for the extensor part of the femurtibia control loop. The habituation of FETi during repetitive stimulation is produced by a decrease in response amplitude together with a hyperpolarizing dc-shift. The imput of both neurons behaves like the output of a lead-lag-system with a predominant phasic component, whose high-pass filter has a time constant which depends on input slope. The nonlinear high-pass filter properties which are one important cause of catalepsy can thus be attributed to properties of interneurons and/or chordotonal organ. For most parts of the simulation of the femur-tibia control system (Cruse and Storrer, 1977) the anatomical and physiological correlates could be shown (Fig. 13).     

Neural correlates of habituation of the proleg withdrawal reflex in larvae of the hawk moth, Manduca sexta

The larval proleg withdrawal reflex of the hawk moth, Manduca sexta, exhibits robust habituation. This reflex is evoked by deflecting one or more mechanosensory planta hairs on a proleg tip. We examined neural correlates of habituation in an isolated proleg preparation consisting of one proleg and its segmental ganglion. Repeated deflection of a single planta hair caused a significant decrease in the number of action potentials evoked in the proleg motor nerve (which carries the axons of proleg retractor motor neurons). Significant response decrement was seen for interstimulus intervals of 10 s, 60 s and 5 min. Response decrement failed to occur in the absence of repetitive stimulation, the decremented response recovered spontaneously following a rest, and electrical stimulation of a body wall nerve facilitated the decremented response (a neural correlate of dishabituation). Adaptation of sensory neuron responses occurred during repeated hair deflections. However, when adaptation was eliminated by direct electrical stimulation of sensory neurons, the response in the proleg motor nerve still decreased significantly. Muscle recordings indicated that the response of an identified proleg retractor motor neuron decreased significantly during habituation training. Thus, habituation of the proleg withdrawal reflex includes a central component that is apparent at the level of a single motor neuron. Accepted: 20 December 1996     

High-Frequency Stimulation of Excitable Cells and Networks

High-frequency (HF) stimulation has been shown to block conduction in excitable cells including neurons and cardiac myocytes. However, the precise mechanisms underlying conduction block are unclear. Using a multi-scale method, the influence of HF stimulation is investigated in the simplified FitzhHugh-Nagumo and biophysically-detailed Hodgkin-Huxley models. In both models, HF stimulation alters the amplitude and frequency of repetitive firing in response to a constant applied current and increases the threshold to evoke a single action potential in response to a brief applied current pulse. Further, the excitable cells cannot evoke a single action potential or fire repetitively above critical values for the HF stimulation amplitude. Analytical expressions for the critical values and thresholds are determined in the FitzHugh-Nagumo model. In the Hodgkin-Huxley model, it is shown that HF stimulation alters the dynamics of ionic current gating, shifting the steady-state activation, inactivation, and time constant curves, suggesting several possible mechanisms for conduction block. Finally, we demonstrate that HF stimulation of a network of neurons reduces the electrical activity firing rate, increases network synchronization, and for a sufficiently large HF stimulation, leads to complete electrical quiescence. In this study, we demonstrate a novel approach to investigate HF stimulation in biophysically-detailed ionic models of excitable cells, demonstrate possible mechanisms for HF stimulation conduction block in neurons, and provide insight into the influence of HF stimulation on neural networks.     

Modulation of the Aplysia gill withdrawal reflex by dopamine

The ability of dopamine to modulate gill contractions was tested in Aplysia. When dopamine was perfused through the gill vasculature, gill contractions caused by siphon stimulation (gill withdrawal reflex) and by depolarization of the gill motor neuron L7 were increased in amplitude, as compared with those evoked during seawater perfusion. Habituation of gill movements, brought about by repetitive stimulation of the siphon or of L7, was prevented by dopamine. Despite the absence of reflex habituation, the number of action potentials in central gill motor neurons, evoked by siphon stimulation, showed normal decrement. Dopamine's effects were blocked when the ctenidial nerve was cut or when L7 hyperpolarized. These data suggest that dopamine acts peripherally to increase the efficacy of L7's synaptic transmission onto gill muscle or elements of the gill neural plexus.     

Dynamical compensation in physiological circuits

Biological systems can maintain constant steady‐state output despite variation in biochemical parameters, a property known as exact adaptation. Exact adaptation is achieved using integral feedback, an engineering strategy that ensures that the output of a system robustly tracks its desired value. However, it is unclear how physiological circuits also keep their output dynamics precise—including the amplitude and response time to a changing input. Such robustness is crucial for endocrine and neuronal homeostatic circuits because they need to provide a precise dynamic response in the face of wide variation in the physiological parameters of their target tissues; how such circuits compensate their dynamics for unavoidable natural fluctuations in parameters is unknown. Here, we present a design principle that provides the desired robustness, which we call dynamical compensation (DC). We present a class of circuits that show DC by means of a nonlinear feedback loop in which the regulated variable controls the functional mass of the controlling endocrine or neuronal tissue. This mechanism applies to the control of blood glucose by insulin and explains several experimental observations on insulin resistance. We provide evidence that this mechanism may also explain compensation and organ size control in other physiological circuits.     

Paraspinal muscle reflex dynamics

Neuromuscular control of spinal stability may be represented as a control system wherein the paraspinal muscle reflex acts as feedback response to kinetic and kinematic disturbances of the trunk. The influence of preparatory muscle recruitment for the control of spinal stability has been previously examined, but there are few reported studies that characterize paraspinal reflex gain as feedback response. In the current study, the input-output dynamics of paraspinal reflexes were quantified by means of the impulse response function (IRF), with trunk perturbation force representing the input signal and EMG the output signal. Surface EMGs were collected from the trunk muscles in response to a brief anteriorly directed impact force applied to the trunk of healthy participants. Reflex behavior was measured in response to three levels of force impulse, 6.1, 9.2 and 12.0 Ns, and two different levels of external trunk flexion preload, 0 and 110 N anterior force. Reflex EMG was quantifiable in response to 91% of the perturbations. Mean reflex onset latency was 30.7+/-21.3 ms and reflex amplitude increased with perturbation amplitude. Impulse response function gain, G(IRF), was defined as the peak amplitude of the measured IRF and provided a consistent measure of response behavior. EMG reflex amplitude and G(IRF) increased with force impulse. Mean G(IRF) was 2.27+/-1.31% MVC/Ns and demonstrated declining trend with flexion preload. Results agree with a simple systems model of the neuromechanical feedback behavior. The relative contribution of the reflex dynamics to spinal stability must be investigated in future research.     

Phase-linked variations in the amplitude of the digastric nerve jaw-opening reflex response during fictive mastication in the rabbit

The diagastric nerve reflex response to stimulation of the upper lip was studied in urethan-anesthetized rabbits paralysed with pancuronium bromide. Rhythmic bursts of masticatory activity were evoked in the nerve by repetitive electrical stimulation of the motor cortex. The amplitude and latency of the reflex responses during fictive mastication were compared with preceding control values. When stimuli close to threshold were given, the largest and earliest responses occurred during the digastric burst. When intense stimuli were employed, the largest responses were out of phase with the burst, although the latency was still shortest when the motoneurons were rhythmically active. Since the pattern is essentially the same as that seen during normal mastication, we conclude that the cyclical modulation of reflex amplitude and latency is not the result of sensory feedback generated by the movements themselves but is instead governed by the central motor program.     

Activity of fusimotor neurons during reflex muscle contraction

The influence of fusimotor activity via the gamma-loop on reflex responses of motoneurons to stretch or vibration stimulation of mm. triceps surae was studied in decerebrate cats. Action potentials of single fusimotor neurons were derived from thin filaments isolated from nerves innervating this muscle group, leaving their main nerve supply intact. Most fusimotor neurons tested were found to be coactivated with motor units during reflex muscle contraction. In the initial period of development of reflex muscle contraction a weak autogenetic inhibitory effect on discharge of fusimotor neurons was found. The results suggest that reduction of the reflex motor signal, leading to a "silent period," is partly the result of a transient decrease in the fusimotor output effect on contracting muscles. A study of changes in fusimotor discharge generation during the ascending phase of reflex muscle contraction may provide data useful for identification of autogenetic reflex influences on these motoneurons and for elucidating the conditions necessary for servoassistance of muscle contractions.Medical Research Institute, Belgrade, Yugoslavia. Translated from Neirofiziologiya, Vol. 16, No. 5, pp. 630–637, September–October, 1984.     

Biophysical basis for three distinct dynamical mechanisms of action potential initiation

Transduction of graded synaptic input into trains of all-or-none action potentials (spikes) is a crucial step in neural coding. Hodgkin identified three classes of neurons with qualitatively different analog-to-digital transduction properties. Despite widespread use of this classification scheme, a generalizable explanation of its biophysical basis has not been described. We recorded from spinal sensory neurons representing each class and reproduced their transduction properties in a minimal model. With phase plane and bifurcation analysis, each class of excitability was shown to derive from distinct spike initiating dynamics. Excitability could be converted between all three classes by varying single parameters; moreover, several parameters, when varied one at a time, had functionally equivalent effects on excitability. From this, we conclude that the spike-initiating dynamics associated with each of Hodgkin's classes represent different outcomes in a nonlinear competition between oppositely directed, kinetically mismatched currents. Class 1 excitability occurs through a saddle node on invariant circle bifurcation when net current at perithreshold potentials is inward (depolarizing) at steady state. Class 2 excitability occurs through a Hopf bifurcation when, despite net current being outward (hyperpolarizing) at steady state, spike initiation occurs because inward current activates faster than outward current. Class 3 excitability occurs through a quasi-separatrix crossing when fast-activating inward current overpowers slow-activating outward current during a stimulus transient, although slow-activating outward current dominates during constant stimulation. Experiments confirmed that different classes of spinal lamina I neurons express the subthreshold currents predicted by our simulations and, further, that those currents are necessary for the excitability in each cell class. Thus, our results demonstrate that all three classes of excitability arise from a continuum in the direction and magnitude of subthreshold currents. Through detailed analysis of the spike-initiating process, we have explained a fundamental link between biophysical properties and qualitative differences in how neurons encode sensory input.     

Trigeminal reflex regulation of the glottis depends on central glycinergic inhibition in the rat

In an unanesthetized decerebrate in situ arterially perfused brain stem preparation of mature rat, strychnine (0.05-0.2 microM) blockade of glycine receptors caused postinspiratory glottal constriction to occur earlier, shifting from early expiration to inspiration. This resulted in a paradoxical inspiratory-related narrowing of the upper airway. Stimulation of the trigeminal ethmoidal nerve (EN5; 20 Hz, 100 micros, 0.5-2 V) evoked a diving response, which included a reflex apnea, glottal constriction, and bradycardia. After strychnine administration, this pattern was converted to a maintained phrenic nerve discharge and a reduced glottal constriction that was interrupted intermittently by transient abductions. The onset of firing of postinspiratory neurons shifted from early expiration into neural inspiration in the presence of strychnine, but neurons maintained their tonic activation during EN5 stimulation, as observed during control. Inspiratory neurons that were hyperpolarized by EN5 stimulation in control conditions were powerfully excited after loss of glycinergic inhibition. Thus the integrity of glycinergic inhibition within the pontomedullary respiratory network is critical for the coordination of cranial and spinal motor outflows during eupnea but also for protective reflex regulation of the upper airway.     

Motion control of the ankle joint with a multiple contact nerve cuff electrode: a simulation study

The flat interface nerve electrode (FINE) has demonstrated significant capability for fascicular and subfascicular stimulation selectivity. However, due to the inherent complexity of the neuromuscular skeletal systems and nerve–electrode interface, a trajectory tracking motion control algorithm of musculoskeletal systems for functional electrical stimulation using a multiple contact nerve cuff electrode such as FINE has not yet been developed. In our previous study, a control system was developed for multiple-input multiple-output (MIMO) musculoskeletal systems with little prior knowledge of the system. In this study, more realistic computational ankle/subtalar joint model including a finite element model of the sciatic nerve was developed. The control system was tested to control the motion of ankle/subtalar joint angles by modulating the pulse amplitude of each contact of a FINE placed on the sciatic nerve. The simulation results showed that the control strategy based on the separation of steady state and dynamic properties of the system resulted in small output tracking errors for different reference trajectories such as sinusoidal and filtered random signals. The proposed control method also demonstrated robustness against external disturbances and system parameter variations such as muscle fatigue. These simulation results under various circumstances indicate that it is possible to take advantage of multiple contact nerve electrodes with spatial selectivity for the control of limb motion by peripheral nerve stimulation even with limited individual muscle selectivity. This technology could be useful to restore neural function in patients with paralysis.     

Modulation of heart activity during withdrawal reflexes in the snail <Emphasis Type="Italic">Helix aspersa</Emphasis>

The beating activity of the molluscan heart is myogenic, but it is influenced by nervous signals of central origin. Previous studies have demonstrated changes in cardiac output during feeding and other behaviors. Here, we describe a short latency, transient cardiac response that accompanies withdrawal reflexes. When evoked by electrical stimulation of peripheral nerves, the response was detected within one or two heartbeats. Beat amplitudes increased on average 11.6%, and inter-beat intervals decreased on average 2.1%. The mean duration of the response was 28.1 s. A transient inhibitory phase often preceded the excitatory response. Results from testing various nerves and tissues show that the cardiac responses invariably occur whenever contractions of the tentacle retractor muscle are elicited. Even stimulation of the ovotestis and the kidney elicit responses despite their protected locations within the mantle cavity. Three excitatory cardioactive neurons are identified in the central nervous system of Helix aspersa, and their involvement in the reflex response is documented. The results suggest that the heart output is initially inhibited to relax the hydroskeleton and thereby aid withdrawal movements. A delayed increase in cardiac output then facilitates the re-inflation, hence eversion, of the withdrawn body parts.     

Noradrenergic neurons in the rat solitary nucleus participate in the esophageal-gastric relaxation reflex

Activation of esophageal mechanosensors excites neurons in and near the central nucleus of the solitary tract (NSTc). In turn, NSTc neurons coordinate the relaxation of the stomach [i.e., the receptive relaxation reflex (RRR)] by modulating the output of vagal efferent neurons of the dorsal motor nucleus of the vagus (DMN). The NSTc area contains neurons with diverse neurochemical phenotypes, including a large population of catecholaminergic and nitrergic neurons. The aim of the present study was to determine whether either one of these prominent neuronal phenotypes was involved in the RRR. Immunohistochemical techniques revealed that repetitive esophageal distension caused 53% of tyrosine hydroxylase-immunoreactive (TH-ir) neurons to colocalize c-Fos in the NSTc. No nitric oxide synthase (NOS)-ir neurons in the NSTc colocalized c-Fos in either distension or control conditions. Local brain stem application (2 ng) of alpha-adrenoreceptor antagonists (i.e., alpha1-prazosin or alpha2-yohimbine) significantly reduced the magnitude of the esophageal distension-induced gastric relaxation to approximately 55% of control conditions. The combination of yohimbine and prazosin reduced the magnitude of the reflex to approximately 27% of control. In contrast, pretreatment with either the NOS-inhibitor NG-nitro-l-arginine methyl ester or the beta-adrenoceptor antagonist propranolol did not interfere with esophageal distension-induced gastric relaxation. Unilateral microinjections of the agonist norepinephrine (0.3 ng) directed at the DMN were sufficient to mimic the transient esophageal-gastric reflex. Our data suggest that noradrenergic, but not nitrergic, neurons of the NSTc play a prominent role in the modulation of the RRR through action on alpha1- and alpha2-adrenoreceptors. The finding that esophageal afferent stimulation alone is not sufficient to activate NOS-positive neurons in the NSTc suggests that these neurons may be strongly gated by other central nervous system inputs, perhaps related to the coordination of swallowing or emesis with respiration.     

Dopamine modulation of gill reflex behavior in Aplysia.

We have studied the effects of dopamine on the gill withdrawal reflex evoked by tactile siphon stimulation in the margine mollusc Aplysia. Physiological concentrations of dopamine (diluted in seawater) were perfused through the gill during siphon stimulation series. The amplitude of the reflex was potentiated by dopamine and habituation of the reflex was prevented. This occurred with no change in the activity evoked in central motor neurons. These results lead us to conclude that the dopaminergic motor neuron L9 is modulating habituation in the periphery and that the central nervous system facilitatory control of the peripheral nervous system may act via a dopaminergic pathway.     

Temporal processing and adaptation in the songbird auditory forebrain

Songbird auditory neurons must encode the dynamics of natural sounds at many volumes. We investigated how neural coding depends on the distribution of stimulus intensities. Using reverse-correlation, we modeled responses to amplitude-modulated sounds as the output of a linear filter and a nonlinear gain function, then asked how filters and nonlinearities depend on the stimulus mean and variance. Filter shape depended strongly on mean amplitude (volume): at low mean, most neurons integrated sound over many milliseconds, while at high mean, neurons responded more to local changes in amplitude. Increasing the variance (contrast) of amplitude modulations had less effect on filter shape but decreased the gain of firing in most cells. Both filter and gain changes occurred rapidly after a change in statistics, suggesting that they represent nonlinearities in processing. These changes may permit neurons to signal effectively over a wider dynamic range and are reminiscent of findings in other sensory systems.     

The development of central nervous system control of the gill withdrawal reflex evoked by siphon stimulation in Aplysia

In older Aplysia, the central nervous system (CNS) (abdominal ganglion) exerts suppressive and facilitatory control over the peripheral nervous system (PNS) which initially mediates the gill withdrawal reflex and its subsequent habituation evoked by tactile stimulation of the siphon. In young animals, both the suppressive and facilitatory CNS control were found to be absent. In older animals, removal of branchial nerve (Br) input to the gill resulted in a significantly reduced reflex latency and, with ctenidial (Ct) and siphon (Sn) nerves intact, a significantly increased reflex amplitude and an inability of the reflex to habituate with repeated siphon stimulation. In young animals, removal of Br had no effect on reflex latency and with Ct and Sn intact, the reflex amplitude latency was not increased and the reflex habituated. Older animals can easily discriminate between different intensity stimuli applied to the siphon as evidenced by differences in reflex amplitude, rates of habituation, and evoked neural activity. On the other hand, young animals cannot discriminate well between different stimulus intensities. The lack of CNS control in young animals was found to be due to incompletely developed neural processes within the abdominal ganglion and not the PNS. The lack of CNS control in young Aplysia results in gill reflex behaviours being less adaptive in light of changing stimulus conditions, but may be of positive survival value in that the young will not habituate as easily. The fact that CNS control is present in older animals strengthens the idea that in any analysis of the underlying neural mechanisms of habituation the entire integrated CNS-PNS must be taken into account.     

The gill withdrawal reflex is suppressed in sexually active Aplysia

In Aplysia, the central nervous system and peripheral nervous system interact and form an integrated system that mediates adaptive gill withdrawal reflex behaviours evoked by tactile stimulation of the siphon. The central nervous system (CNS) exerts suppressive and facilitatory control over the peripheral nervous system (PNS) in the mediation of these behaviours. We found that the CNS's suppressive control over the PNS was increased significantly in animals engaged in sexual activity as either a male or female. In control animals, the evoked gill withdrawal reflex met a minimal response amplitude criterion, while in sexually active animals the reflex did not meet this criterion. At the neuronal level, the increased CNS suppressive control was manifested as a decrease in excitatory input to the central gill motor neurons.     

Fatigue compensation during FES using surface EMG

Muscle fatigue limits the effectiveness of FES when applied to regain functional movements in spinal cord injured (SCI) individuals. The stimulation intensity must be manually increased to provide more force output to compensate for the decreasing muscle force due to fatigue. An artificial neural network (ANN) system was designed to compensate for muscle fatigue during functional electrical stimulation (FES) by maintaining a constant joint angle. Surface electromyography signals (EMG) from electrically stimulated muscles were used to determine when to increase the stimulation intensity when the muscle’s output started to drop.

In two separate experiments on able-bodied subjects seated in hard back chairs, electrical stimulation was continuously applied to fatigue either the biceps (during elbow flexion) or the quadriceps muscle (during leg extension) while recording the surface EMG. An ANN system was created using processed surface EMG as the input, and a discrete fatigue compensation control signal, indicating when to increase the stimulation current, as the output. In order to provide training examples and test the systems’ performance, the stimulation current amplitude was manually increased to maintain constant joint angles. Manual stimulation amplitude increases were required upon observing a significant decrease in the joint angle. The goal of the ANN system was to generate fatigue compensation control signals in an attempt to maintain a constant joint angle.

On average, the systems could correctly predict 78.5% of the instances at which a stimulation increase was required to maintain the joint angle. The performance of these ANN systems demonstrates the feasibility of using surface EMG feedback in an FES control system.     

Transient adaptation and sensitization in the retina of Necturus

Responses to repetitive stimulation were monitored at several retinal levels in the eyecup of the mudpuppy Necturus maculosus. When alternating sequences of low-intensity small and large spots were presented, two effects were found, which could be localized to the proximal retina: (a) response decrement (RD), in which, after the first small spot response, subsequent small spot responses are decreased in amplitude and (b) transient response enhancement (TRE), in which the first small spot response after a large spot sequence is larger than preceding or subsequent small spot responses. RD and TRE are absent or weak in sustained on or off responses (horizontal and bipolar cells, and ON and OFF ganglion cell post-stimulus time histograms (PSTH) but are particularly well developed in the on/off responses of the proximal retina (proximal negative response, M-wave, PSTHs of ON/OFF ganglion cells, and intracellular responses from on/off neurons and Muller cells). RD and TRE appear to arise from a stimulus-evoked slow depolarization in on/off neurons that interacts with the amplitude of succeeding responses. We conclude that RD and TRE are a form of neural adaptation that is largely specific to the on/off channels of the proximal retina.