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PubMed2003

The pain-relieving effects induced by electroacupuncture with different intensities at homotopic and heterotopic acupoints in humans.

The purpose of the present study was to investigate the relationship between the distribution of the analgesic area when different intensities of stimulation were applied to homotopic and heterotopic acupoints. The experiments were performed on volunteers; the left sural nerve was stimulated by a volley of eight rectangular pulses delivered at a frequency of 400 Hz. Electromyographic reflex responses (EMGs) were recorded from the ipsi-lateral biceps femoris muscle. Electroacupuncture stimuli were given on the skin overlying the Zusanli point (St 36), and the strengths chosen were times of the threshold eliciting a nociceptive reflex (T(RIII)) response (0.6, 0.8, 1.0, T(RIII) and T(supra-RIII), respectively). The effects of homotopic and heterotopic stimuli applied to St 36 on the pain sensation and the R(III), reflex elicited by stimulation of the left sural nerve were observed to explore the pain-relief and R(III) reflex-inhibition produced by stimulation of the St 36 point with different intensities. Both the nociceptive reflex and painful sensation evoked by stimulating the sural nerve were similarly inhibited by electroacupuncture at less than T(RIII) applied to the ipsi-lateral acupoint. In other words, acupuncture with an innocuous intensity can produce homotopic pain-alleviating effects and reflex suppression. With contra-lateral electroacupuncture at the St 36 acupoint, innocuous intensities cannot produce heterotopic pain-relieving effects; these inhibitions were only observed at electroacupuncture intensities similar to the T(RIII) threshold. These results suggest that local acupuncture-induced analgesia is effective with activation of large afferent fibers, whereas heterotopic acupuncture-induced analgesia is only effective with intensities strong enough to excite small afferent fibers. Local analgesic effects of acupoint stimulation involve segmental inhibition, whereas systemic analgesic effects of acupoint stimulation are involved in contra-lateral effects. The latter may recruit the diffuse noxious inhibitory controls (DNIC) system. The specific function of an acupoint is determined by the anatomical relationship between the disease focus and the segmental location of the acupoint.

Acupuncture Points↗
PubMed1984

Electrical properties and synaptic connections to neurons in parasympathetic colonic ganglia of the cat.

Intracellular recording techniques were used in vitro to analyze the electrophysiological properties and synaptic connections to cat parasympathetic neurons in ganglia located on the serosal surface of the distal colon. Neurons were classified into two types. The first type exhibited spontaneous action potentials at regular and irregular interspike intervals. Spontaneous action potentials were 1) not abolished by superfusion of the ganglia with a modified Krebs solution containing low Ca2+, high Mg2+, or nicotinic ganglionic blocking agents, 2) reduced or abolished by intracellular injection of hyperpolarizing current, and 3) increased by intracellular injection of depolarizing current. We suggest that the generation of spontaneous action potentials may be due to an endogenous depolarizing mechanism and not to cholinergic synaptic input from other neurons located in the ganglia. The second type of neuron termed "quiescent" exhibited a stable transmembrane potential and elicited action potentials in response to electrical stimulation of nerve trunks. Both quiescent and spontaneously discharging neurons receive synaptic input from preganglionic fibers in the pelvic nerve and project their postganglionic axons to colonic nerve fibers that innervate effector structures in the colon.

Action Potentials↗
PubMed1984

Neural control of relaxation in cat airways smooth muscle.

Functional innervation of cat airways smooth muscle was examined in isolated segments of trachea and bronchi using electrical field stimulation (EFS) techniques. Field stimulation caused contraction in tissues at resting tone and biphasic responses (contraction followed by relaxation) in tissues precontracted with 5-hydroxytryptamine (5-HT). Contractions were abolished by 10(-6) M atropine. Inhibitory responses were dependent on impulse voltage, duration, and frequency. At low voltages (less than or equal to 10 V) and pulse durations (less than or equal to 0.3 ms), EFS induced relaxations were abolished by 3 X 10(-6) M tetrodotoxin (TTX). Greater stimulus parameters elicited TTX-resistant relaxations. Pretreatment of the tissues with 10(-6) M propranolol and 10(-5) M guanethidine caused rightward shifts in relaxation frequency-response curves. These findings indicate that cat airways are innervated by excitatory cholinergic, inhibitory adrenergic, and inhibitory nonadrenergic noncholinergic (NANC) nerves. Pretreatment of the tissues with hexamethonium, cimetidine, indomethacin, or nordihydroguaiaretic acid did not affect NANC relaxation responses. It is concluded that NANC inhibitory responses in cat airway smooth muscle are mediated through intrinsic postganglionic nerve fibers and occur independently of histamine H2-receptor activation and without involvement of cyclooxygenase or lipoxygenase products of arachidonic acid metabolism.

Animals↗
PubMed2005

Controlling synaptic input patterns in vitro by dynamic photo stimulation.

Recent experimental and theoretical work indicates that both the intensity and the temporal structure of synaptic activity strongly modulate the integrative properties of single neurons in the intact brain. However, studying these effects experimentally is complicated by the fact that, in experimental systems, network activity is either absent, as in the acute slice preparation, or difficult to monitor and to control, as in in vivo recordings. Here, we present a new implementation of neurotransmitter uncaging in acute brain slices that uses functional projections to generate tightly controlled, spatio-temporally structured synaptic input patterns in individual neurons. For that, a set of presynaptic neurons is activated in a precisely timed sequence through focal photolytic release of caged glutamate with the help of a fast laser scanning system. Integration of synaptic inputs can be studied in postsynaptic neurons that are not directly stimulated with the laser, but receive input from the targeted neurons through intact axonal projections. Our new approach of dynamic photo stimulation employs functional synapses, accounts for their spatial distribution on the dendrites, and thus allows study of the integrative properties of single neurons with physiologically realistic input. Data obtained with our new technique suggest that, not only the neuronal spike generator, but also synaptic transmission and dendritic integration in neocortical pyramidal cells, can be highly reliable.

Action Potentials↗
PubMed2004

Background synaptic activity modulates the response of a modeled purkinje cell to paired afferent input.

We studied the possible effects of background excitatory and inhibitory synaptic activity on Purkinje cell responses to paired pulse inputs using a morphologically and physiologically detailed compartmental model. Paired-pulse inputs were provided via synapses associated with the ascending segment of the granule cell axon in the presence of variable amounts of background synaptic input provided by parallel fibers and inhibitory interneurons. The results predict the amplitude and dynamics of the somatic and dendritic responses to paired ascending segment inputs are modulated by the level of background synaptic activity, the basal somatic firing rate of the Purkinje cell model does not indicate the type or degree of modulation, and the modulatory effects are mediated through dendritic calcium and calcium-activated potassium currents. These results have important consequences for the functional organization of cerebellar cortex as well as the more general issue of the modulatory as distinct from driving effects of synapses now also being considered in other regions of the mammalian brain including the cerebral cortex.

Action Potentials↗
PubMed2005

Membrane potential oscillations in reticulospinal and spinobulbar neurons during locomotor activity.

Feedback from the spinal locomotor networks provides rhythmic modulation of the membrane potential of reticulospinal (RS) neurons during locomotor activity. To further understand the origins of this rhythmic activity, the timings of the oscillations in spinobulbar (SB) neurons of the spinal cord and in RS neurons of the posterior and middle rhombencephalic reticular nuclei were measured using intracellular microelectrode recordings in the isolated brain stem-spinal cord preparation of the lamprey. A diffusion barrier constructed just caudal to the obex allowed induction of locomotor activity in the spinal cord by bath application of an excitatory amino acid to the spinal bath. All of the ipsilaterally projecting SB neurons recorded had oscillatory membrane potentials with peak depolarizations in phase with the ipsilateral ventral root bursts, whereas the contralaterally projecting SB neurons were about evenly divided between those in phase with the ipsilateral ventral root bursts and those in phase with the contralateral bursts. In the brain stem under these conditions, 75% of RS neurons had peak depolarizations in phase with the ipsilateral ventral root bursts while the remainder had peak depolarizations during the contralateral bursts. Addition of a high-Ca2+, Mg2+ solution to the brain stem bath to reduce polysynaptic activity had little or no effect on oscillation timing in RS neurons, suggesting that direct inputs from SB neurons make a major contribution to RS neuron oscillations under these conditions. Under normal conditions when the brain is participating in the generation of locomotor activity, these spinal inputs will be integrated with other inputs to RS neurons.

Analysis of Variance↗
PubMed2004

Role of mossy fiber sprouting and mossy cell loss in hyperexcitability: a network model of the dentate gyrus incorporating cell types and axonal topography.

Mossy cell loss and mossy fiber sprouting are two characteristic consequences of repeated seizures and head trauma. However, their precise contributions to the hyperexcitable state are not well understood. Because it is difficult, and frequently impossible, to independently examine using experimental techniques whether it is the loss of mossy cells or the sprouting of mossy fibers that leads to dentate hyperexcitability, we built a biophysically realistic and anatomically representative computational model of the dentate gyrus to examine this question. The 527-cell model, containing granule, mossy, basket, and hilar cells with axonal projections to the perforant-path termination zone, showed that even weak mossy fiber sprouting (10-15% of the strong sprouting observed in the pilocarpine model of epilepsy) resulted in the spread of seizure-like activity to the adjacent model hippocampal laminae after focal stimulation of the perforant path. The simulations also indicated that the spatially restricted, lamellar distribution of the sprouted mossy fiber contacts reported in in vivo studies was an important factor in sustaining seizure-like activity in the network. In contrast to the robust hyperexcitability-inducing effects of mossy fiber sprouting, removal of mossy cells resulted in decreased granule cell responses to perforant-path activation in agreement with recent experimental data. These results indicate the crucial role of mossy fiber sprouting even in situations where there is only relatively weak mossy fiber sprouting as is the case after moderate concussive experimental head injury.

Animals↗
PubMed2003

Cellular and network mechanisms of slow oscillatory activity (<1 Hz) and wave propagations in a cortical network model.

Slow oscillatory activity (<1 Hz) is observed in vivo in the cortex during slow-wave sleep or under anesthesia and in vitro when the bath solution is chosen to more closely mimic cerebrospinal fluid. Here we present a biophysical network model for the slow oscillations observed in vitro that reproduces the single neuron behaviors and collective network firing patterns in control as well as under pharmacological manipulations. The membrane potential of a neuron oscillates slowly (at <1 Hz) between a down state and an up state; the up state is maintained by strong recurrent excitation balanced by inhibition, and the transition to the down state is due to a slow adaptation current (Na(+)-dependent K(+) current). Consistent with in vivo data, the input resistance of a model neuron, on average, is the largest at the end of the down state and the smallest during the initial phase of the up state. An activity wave is initiated by spontaneous spike discharges in a minority of neurons, and propagates across the network at a speed of 3-8 mm/s in control and 20-50 mm/s with inhibition block. Our work suggests that long-range excitatory patchy connections contribute significantly to this wave propagation. Finally, we show with this model that various known physiological effects of neuromodulation can switch the network to tonic firing, thus simulating a transition to the waking state.

Algorithms↗
PubMed2003

Cellular effects of deep brain stimulation: model-based analysis of activation and inhibition.

Deep brain stimulation (DBS) is an effective therapy for medically refractory movement disorders. However, fundamental questions remain about the effects of DBS on neurons surrounding the electrode. Experimental studies have produced apparently contradictory results showing suppression of activity in the stimulated nucleus, but increased inputs to projection nuclei. We hypothesized that cell body firing does not accurately reflect the efferent output of neurons stimulated with high-frequency extracellular pulses, and that this decoupling of somatic and axonal activity explains the paradoxical experimental results. We studied stimulation using the combination of a finite-element model of the clinical DBS electrode and a multicompartment cable model of a thalamocortical (TC) relay neuron. Both the electric potentials generated by the electrode and a distribution of excitatory and inhibitory trans-synaptic inputs induced by stimulation of presynaptic terminals were applied to the TC relay neuron. The response of the neuron to DBS was primarily dependent on the position and orientation of the axon with respect to the electrode and the stimulation parameters. Stimulation subthreshold for direct activation of TC relay neurons caused suppression of intrinsic firing (tonic or burst) activity during the stimulus train mediated by activation of presynaptic terminals. Suprathreshold stimulation caused suppression of intrinsic firing in the soma, but generated efferent output at the stimulus frequency in the axon. This independence of firing in the cell body and axon resolves the apparently contradictory experimental results on the effects of DBS. In turn, the results of this study support the hypothesis of stimulation-induced modulation of pathological network activity as a therapeutic mechanism of DBS.

Action Potentials↗
PubMed2006

Resonance or integration? Self-sustained dynamics and excitability of neural microcircuits.

We investigated spontaneous activity and excitability in large networks of artificial spiking neurons. We compared three different spiking neuron models: integrate-and-fire (IF), regular-spiking (RS), and resonator (RES). First, we show that different models have different frequency-dependent response properties, yielding large differences in excitability. Then, we investigate the responsiveness of these models to a single afferent inhibitory/excitatory spike and calibrate the total synaptic drive such that they would exhibit similar peaks of the postsynaptic potentials (PSP). Based on the synaptic calibration, we build large microcircuits of IF, RS, and RES neurons and show that the resonance property favors homeostasis and self-sustainability of the network activity. On the other hand, integration produces instability while it endows the network with other useful properties, such as responsiveness to external inputs. We also investigate other potential sources of stable self-sustained activity and their relation to the membrane properties of neurons. We conclude that resonance and integration at the neuron level might interact in the brain to promote stability as well as flexibility and responsiveness to external input and that membrane properties, in general, are essential for determining the behavior of large networks of neurons.

Action Potentials↗