High Stimulus Strengths Research Articles

Examining effects of preconscious mere exposure: An inattentional blindness approach.

An increase in affective preference for stimuli, which a person has been repeatedly exposed to, is known as mere exposure effect. This effect has been shown for stimuli that are processed subliminally, that is, below the threshold of awareness. This study fills a current research gap by investigating mere exposure effects under processing that is preconscious, which follows from a high stimulus strength but absence of top-down amplification. In three experiments (N = 240 in total) preconscious processing was evoked using an inattentional blindness paradigm, which allowed the processing of stimuli (nonwords or Chinese symbols) under complete inattention. Contrary to our hypothesis, we did not find a mere exposure effect in our experiments. We expand the current state of knowledge by discussing the distractor devaluation effect and the attentional set of participants as possible reasons for the absence of the mere exposure effect. Directions for future investigations are outlined.

Autosomal Recessive NRL Mutations in Patients with Enhanced S-Cone Syndrome.

Enhanced S-cone syndrome (ESCS) is mainly associated with mutations in the NR2E3 gene. However, rare mutations in the NRL gene have been reported in patients with ESCS. We report on an ESCS phenotype in additional patients with autosomal recessive NRL (arNRL) mutations. Three Moroccan patients of two different families with arNRL mutations were enrolled in this study. The mutation in the DNA of one patient, from a consanguineous marriage, was detected by homozygosity mapping. The mutation in the DNA of two siblings from a second family was detected in a targeted next-generation sequencing project. Full ophthalmic examination was performed, including best-corrected visual acuity, slit-lamp biomicroscopy, funduscopy, Goldmann kinetic perimetry, optical coherence tomography, fundus autofluorescence, and extended electroretinography including an amber stimulus on a blue background and a blue stimulus on an amber background. One patient carried a homozygous missense mutation (c.508C>A; p.Arg170Ser) in the NRL gene, whereas the same mutation was identified heterozygously in the two siblings of a second family, in combination with a one base-pair deletion (c.654del; p.Cys219Valfs*4) on the other allele. All patients had reduced visual acuity and showed a typical clumped pigmentary retinal degeneration (CPRD). Foveal schisis-like changes were observed in the oldest patient. An electroretinogram (ERG) under dark-adapted conditions showed absent responses for low stimulus strengths and reduced responses for high stimulus strengths, with constant b-wave latencies despite increasing stimulus strength. A relatively high amplitude was detected with a blue stimulus on an amber background, while an amber stimulus on a blue background showed reduced responses. The arNRL mutations cause a phenotype with typical CPRD. This phenotype has previously been described in patients with ESCS caused by NR2E3 mutations, and rarely by NRL mutations. Based on our findings in ERG testing, we conclude that S-cone function is enhanced in our patients in a similar manner as in patients with NR2E3-associated ESCS, confirming previous reports of NRL as a second gene to cause ESCS.

Improvement of cardiac function by increasing stimulus strength during left ventricular pacing in cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) is an established therapy in patients with severe heart failure due to left ventricular (LV) dyssynchrony. Increasing stimulus strength (SS) of LV pacing could capture an enlarged myocardial area and provide rapid electrical conduction. The aim of the present study was to investigate whether increasing SS of LV pacing improves LV mechanical dyssynchrony and cardiac function in patients treated with CRT.We enrolled 26 patients with CRT and changed the SS of LV pacing: 2.5 V (standard SS) and 5 V (high SS). Electrocardiography and echocardiography were performed to assess QRS duration, LV mechanical dyssynchrony, and cardiac function under each condition.The QRS duration (138.6 ± 21.4 ms versus 126.8 ± 23.1 ms, P < 0.001), septal-posterior wall motion delay (126.5 ± 42.7 ms versus 111.4 ± 55.3 ms, P = 0.012), standard deviation of time from QRS (69.6 ± 21.8 ms versus 55.6 ± 19.4 ms, P < 0.001), LV ejection fraction (29.4 ± 10.6% versus 33.4 ± 11.6%, P = 0.005), and LV stroke volume (50.7 ± 15.5 mL versus 63.8 ± 18.3 mL, P < 0.001) improved significantly in high SS compared with standard SS.Increasing SS of LV pacing in CRT improves LV mechanical dyssynchrony and cardiac function. The capture of an enlarged myocardial area by increasing SS of LV pacing might offer an acute hemodynamic benefit to patients treated with CRT.

Voltage-gated sodium channels contribute to the b-wave of the rodent electroretinogram by mediating input to rod bipolar cell GABAc receptors

Voltage-gated sodium (Nav) channels are known to augment cone bipolar cell light responses, increasing the electroretinogram (ERG) b-wave in response to stimulus strengths above the cone threshold. However previous in vivo studies on a number of animal models have not found a role for Nav channels in augmenting the b-wave in scotopic conditions below the cone threshold. We recorded ERGs from mice and rats using a series of TTX concentrations and tested retinal output to ensure complete Nav channel block. We found that TTX concentrations sufficient to completely suppress retinal output caused large (∼40%) decrease in the scotopic electroretinogram (ERG) response to high stimulus strengths (1.0 log cd s/m2). In addition the b-wave was reduced by ∼20% even at stimulus strengths that should predominately excite the rod pathway (−2.2 log cd s/m2). Modulating stimulus strength and background luminance showed that Nav channel contribution to the b-wave is strongest in mesopic conditions with low strength stimuli. Blocking GABAc receptors indicted that Nav channels predominately contribute to the b-wave by supporting GABAc input to rod bipolar cells in addition to directly amplifying the light response of cone ON bipolar cells. We also determined that saturating levels of TTX reduced the rat b-wave below cone threshold. Nav channels increase the ERG b-wave in both rod and cone bipolar cell-dominated circuits. In circuits involving rod bipolar cells the effect is mediated indirectly via GABAergic inhibitory cells, while Nav channels directly located on cone bipolar cells amplify light responses in the cone pathways.

Influence of stimulus intensity on the soleus H-reflex amplitude and modulation during locomotion

Diverging results have been reported regarding the modulation and amplitude of the soleus H-reflex measured during human walking and running. A possible explanation to this could be the use of too high stimulus strength in some studies while not in others. During activities like walking and running it is necessary to use a small M-wave to control the effective stimulus strength during all phases of the movement. This implies that the descending part of the H-reflex recruitment curve is being used, which may lead to an unwanted suppression of the H-reflex due to limitations imbedded within the H-reflex methodology itself.Accordingly, the purpose of the present study was to study the effect on the soleus H-reflex during walking and running using stimulus intensities normally considered too high (up to 45% Mmax).Using M-waves of 25–45% Mmax as opposed to 5–25% Mmax showed a significant suppression of the peak H-reflex during the stance phase of walking, while no changes were observed during running. No differences were observed regarding modulation pattern. So a possible use of too high stimulus intensity cannot explain the differences mentioned. The surprising result in running may be explained by the much higher voluntary muscle activity, which implies the existence of a V-wave influencing the H-reflex amplitude in positive direction.

Differential changes in retina function with normal aging in humans

We evaluated the full field electroretinogram (ERG) to assess age-related changes in retina function in humans. ERG recordings were performed on healthy subjects with normal fundus appearance, lack of cataract and 20/20 acuity, aged 20-39 years (n = 27; mean age 25 ± 5, standard deviation), 40-59 years (n = 20; mean 53 ± 5), and 60-82 years (n = 18; mean 69 ± 5). Multiple ERG tests were applied, including light and dark-adapted stimulus-response function, dark adaptation and dynamic of recovery from a single bright flash under dark-adapted conditions. Changes in ERG properties were found in the oldest age group when compared with the two younger age groups. (1) The photopic hill effect was less pronounced. (2) Both photopic a-wave and b-wave amplitudes and implicit times were increased at high stimulus strengths. (3) Dark adaptation time was delayed for pure rod and L/M cone-driven responses, respectively. (4) Dark-adapted a-wave but not b-wave amplitudes were reduced, yielding higher B/A ratios. (5) Dark-adapted a- and b-waves implicit times were prolonged: there was a direct proportional correlation between minimal a-wave implicit times and age. (6) The dynamic of dark current recovery from a bright flash, under dark-adapted conditions, was transiently faster at intervals between 0.9 and 2 s. These results denote that aging of the healthy retina is accompanied by specific functional changes, which must be taken into account to optimally diagnose potential pathologies.

Mechanical amplification by hair cells in the semicircular canals

Sensory hair cells are the essential mechanotransducers of the inner ear, responsible not only for the transduction of sound and motion stimuli but also, remarkably, for nanomechanical amplification of sensory stimuli. Here we show that semicircular canal hair cells generate a mechanical nonlinearity in vivo that increases sensitivity to angular motion by amplification at low stimulus strengths. Sensitivity at high stimulus strengths is linear and shows no evidence of amplification. Results suggest that the mechanical work done by hair cells contributes approximately 97 zJ/cell of amplification per stimulus cycle, improving sensitivity to angular velocity stimuli below approximately 5 degrees /s (0.3-Hz sinusoidal motion). We further show that mechanical amplification can be inhibited by the brain via activation of efferent synaptic contacts on hair cells. The experimental model was the oyster toadfish, Opsanus tau. Physiological manifestation of mechanical amplification and efferent control in a teleost vestibular organ suggests the active motor process in sensory hair cells is ancestral. The biophysical basis of the motor(s) remains hypothetical, but a key discriminating question may involve how changes in somatic electrical impedance evoked by efferent synaptic action alter function of the motor(s).

Representational overlap of adjacent fingers in multiple areas of human primary somatosensory cortex depends on electrical stimulus intensity: an fMRI study

Functional magnetic resonance imaging (fMRI) was used to examine the influence of non-painful electrical stimulus intensity on the BOLD response in human primary somatosensory cortex (SI). In ten healthy subjects, index and middle finger of the right hand were stimulated separately at two different stimulus intensities. The activated volume of single finger representations as well as the volume of representational overlap of the two activations increased following an increase in stimulus intensity. This effect was seen in two different subdivisions of SI, one in the depth of the central sulcus, presumably corresponding to Brodmann area (BA) 3b, and one on the crown of the postcentral gyrus, presumably corresponding to BA 1/2. Relative overlap (ratio of overlap volume to volume of individual finger representation) was larger in BA 1/2 than in BA 3b. Additionally, in both areas relative overlap increased significantly from low to high stimulus intensity. Relative overlap did not change when different correlation thresholds were employed arguing against an unspecific ‘spillover effect’. Analysis of signal intensity time courses indicated that the response difference to high versus low stimulus strength was not present during the initial seconds of stimulation, during which both led to a similar signal intensity increase. Only during the following maintenance level of the response did the response to high stimulus intensity reach a significantly higher plateau level than the one due to low intensity stimulation, an effect which was present in both areas, BA 3b and BA 1/2, respectively.

Asymmetries in sensory pathways from skin to motoneurons on each side of the body determine the direction of an avoidance response in hatchling Xenopus tadpoles.

1. When swimming is initiated by tail stimulation in hatchling Xenopus tadpoles, the first trunk contraction is usually on the opposite side and directs the animal away from the stimulus. We have investigated how asymmetries in the skin sensory pathways mediate this response. 2. In alpha-bungarotoxin-immobilized tadpoles, intracellular recordings were made of responses to ipsilateral (ISS) and contralateral skin stimulation (CSS) in thirty-two presumed motoneurons. ISS evokes an inhibitory postsynaptic potential (IPSP) followed by an excitatory postsynaptic potential (EPSP) whereas CSS only evokes an EPSP. Blocking the short latency IPSP evoked by ISS with strychnine reduced the difference in spike latency on the two sides but spikes still occurred first to CSS. 3. Motoneuron EPSPs evoked by ISS and CSS were therefore recorded during microperfusion of strychnine to block the short latency IPSP. We found: (a) the CSS-EPSPs have lower threshold, larger amplitude at a given intensity of stimulus, faster rising phase, and shorter latencies than those of ISS-EPSPs; (b) the ISS-EPSP onset latencies were longer than CSS-EPSPs and became shorter as the stimulus intensity increased while those of CSS-EPSPs remained little changed. At high stimulus intensities, EPSPs caused by CSS and ISS became similar; and (c) onset latencies of ISS-EPSPs had higher variance than those of CSS-EPSPs. However, this difference was reduced as the stimulus intensity was increased. 4. Since motoneuron EPSP onset latencies varied with stimulus intensity, we proposed that the pathway from the opposite side had stronger synapses from afferents to sensory interneurons. To test this proposal we built a neuronal population model of the spinal pathway from skin afferents, via sensory interneurons to ipsilateral and contralateral motoneurons incorporating this asymmetry. Inhibition was omitted from the model. 5. Simulated motoneuron EPSPs in response to skin stimulation on each side of the body showed the major asymmetries found experimentally. If the distribution and axonal projections of the interneurons in the two sensory pathways were made the same these differences remained. However, if the synaptic strength from sensory afferents onto interneurons projecting to the two sides were made equal, the difference between the two sides were lost. 6. We propose that the sensory pathway to contralateral motoneurons has more effective excitation from afferents to sensory interneurons which leads to these motoneurons firing first. At higher stimulus strengths, when population recruitment can blur these subtle differences in excitation between the two sides, inhibition normally plays a significant role to ensure that most first responses are still contralateral.

Two types of plasticity in the tentacle withdrawal reflex of Helix aspersa are dissociated by tissue location and response measure

The tentacle withdrawal reflex of the terrestrial snail Helix aspersa was studied in vitro. The reflex is evoked by mechanical stimulation of the nose. Lesion experiments showed that 45% to 75% of the response amplitude is attributable to peripheral pathways alone. The central contribution increases with increasing stimulus intensity. Repeated stimulation produced pure habituation at low stimulus strengths, and habituation mixed with intrinsic sensitization (warm-up effect) at high stimulus strengths. The simultaneous occurrence of habituation and sensitization is consistent with the dual process theory of plasticity. Additional results differentiate the two processes. Habituation can occur without the CNS, whereas intrinsic sensitization requires the CNS. Also, the two processes are differentially effective in their influences on response amplitude and duration: habituation is more effective in determining response amplitude, while sensitization is more effective in determining response duration. Although the establishment of sensitization requires the CNS, 81% of the memory for intrinsic sensitization was localized to the periphery, by lesion experiments. Extrinsic sensitization, caused by stimulation of the medial lip nerve, had similar behavioural effects and a similar memory locus. Both types of sensitization appear to be caused by neuromuscular facilitation mediated by a central pathway.

Strong Activation of Parallel Fibers Produces Localized Calcium Transients and a Form of LTD That Spreads to Distant Synapses

The temporal and spatial changes in intracellular calcium levels during separate activation of parallel fiber (PF) and climbing fiber (CF) inputs to cerebellar Purkinje cells were studied. PF stimulation (1 Hz), at relatively high stimulus strengths, led to accumulations of calcium that were similar in peak levels to those following CF stimulation but that remained spatially localized. Such stimuli consistently induced a durable depression of PF synaptic transmission that partially occluded further depression by conventional conjunctive stimuli and that was independent of nitric oxide. This depression was accompanied by a reduction of synaptic efficacy in spatially isolated PF inputs to the same cell that was independent of postsynaptic calcium but that was mediated by nitric oxide. These data indicate that LTD comprises at least two separate processes and that parameters of PF stimulation that are capable of raising calcium levels in Purkinje cell dendrites are also able to induce long-term changes in synaptic efficacy.

Structural and functional characterization of a muscle tendon proprioceptor in lobster

A morphological and electrophysiological study was made on a unique primary mechanosensory neuron, the anterior gastric receptor (AGR), previously shown to arise from power-stroke muscle gm1 of the gastric mill system in the lobster foregut. Ultrastructural analysis of horseradish peroxidase injected AGR demonstrated that its peripheral dendrites do not ramify in muscle but are confined strictly to the connective tissue/epidermal interface in the tendon of gm1. These terminals are rich in mitochondria and at their very endings are free of glial cell wrapping, suggesting that they are the site at which mechano-transduction occurs. Extracellular axonal recordings from an in vitro neuromuscular preparation consisting of the gm1 muscle still attached to the stomatogastric nervous system, revealed that AGR is activated by passive stretch of gm1. The response to ramp stimuli displays dynamic and static components, both of which increase with the amplitude of applied stretch, while the dynamic component is also velocity sensitive. AGR is also activated by muscle contraction here elicited either by application of exogenous acetylcholine, the excitatory neurotransmitter for gm1, or by electrical stimulation of the motoneurons (GM) themselves. Consistent with a receptor lying in-series with its muscle, therefore, the effective stimulus of AGR in vivo is probably an increase in tension exerted on the tendon during active muscle contraction. In neuromuscular preparations including the bilateral commissural ganglia, stretching gm1 reflexly activates GM motoneurons at low stimulus strengths but leads to an inactivation of GM motoneurons at high stimulus strengths. This is consistent with earlier findings that both responses can be elicited by direct electrical stimulation of AGR. The functional implications of AGR's anatomical relationship with muscle gm1, the receptor's response properties, and its central effects on motor output to gm1 are discussed. Comparison is also drawn between this first reported example of a true tendon receptor in invertebrates and muscle receptors of vertebrates.

Interneurones of the supratrigeminal area mediating reflex inhibition of trigeminal and facial motorneurones in the rat

Whether sensory information from the inferior alveolar nerve is mediated by different types of interneurones in the supratrigeminal area (Su5) and whether different types of these interneurones have different inhibitory actions on jaw-closing motor neurones of the trigeminal motor nucleus was investigated. The intracellular responses of periodontal afferents in the mesencephalic trigeminal nucleus, Su5 interneurones and jaw-closing motor neurones were studied in response to graded, single-shock stimulation of the ipsilateral inferior alveolar nerve. It was found that the inhibitory action of afferent inflow from the inferior alveolar nerve to jaw-closing motor neurones is possibly mediated by two types of Su5 interneurones (T-I and T-II). These Su5 neurones were discriminated on the basis of their firing characteristics. The findings also indicated that: (1) T-I neurones are responsible for short-latency, low-threshold inhibitory postsynaptic potentials (IPSPs) observed in the trigeminal motor nucleus neurones; (2) T-II interneurones mainly contribute to the amplitude of these IPSPs at higher stimulus strengths; (3) the late part of plateau IPSPs in the jaw-closing motor neurones is induced by a characteristic firing of T-11 neurones. It was also shown that afferent inflow from the inferior alveolar nerve, probably mediated by collaterals of T-I and T-II interneurones, also evokes IPSPs in neurones of the intermediate subnucleus of the facial motor nucleus. The characteristics of these IPSPs resemble those of the IPSPs recorded in the jaw-closing motor neurones.

Effect of yohimbine on the contractile response of the mouse vas deferens to short, low frequency trains of nerve impulses.

A study was undertaken to ascertain why in the mouse vas deferens excitatory junction potentials facilitate whereas contractions depress during low frequency stimulation. In a set of contraction studies, where a conditioning stimulus was followed 2 s later by a test stimulus, depression in the first phase of contraction was observed only at high stimulus strengths when many nerves are activated leading to a large secretion. Low stimulus strengths did not produce depression, suggesting that the autoinhibitory effect due to released noradrenaline is absent. At supramaximal stimulus strengths short, low frequency (0.1-0.5 Hz) trains gave varying degrees of depression of the first phase at each stimulus frequency. This depression was reversed by yohimbine (10 microM), indicating that the level of autoinhibition depends on the total amount of noradrenaline secreted. In the absence of autoinhibition, facilitation could be predicted in terms of the residual Ca2+ hypothesis.

Pyramidal neurons in layer 5 of the rat visual cortex. II. Development of electrophysiological properties

Two major classes of pyramidal neurons can be distinguished in layer 5 of the adult rat visual cortex. Cells of the "thick/tufted" type have stout apical dendrites with terminal tufts, and most of them project to the superior colliculus (Larkman and Mason: J Neurosci 10:407, '90; Kasper et al.: J Comp Neurol, this issue, 339:459-474). "Slender/untufted" cells have thinner apical trunks with no obvious terminal tufts, and a substantial proportion of them project to the contralateral visual cortex. These two types also differ in their intrinsic electrophysiological features. In this study we describe the postnatal maturation of the electrophysiological and synaptic properties of layer 5 pyramidal neurons and relate these findings to the morphological development and divergence of the two cell types. Living slices were prepared from the visual cortex of rats aged between postnatal day 3 (P3) and young adults and maintained in vitro. Stable intracellular impalements were obtained from a total of 63 pyramidal cells of layer 5 at various ages, which were injected with biocytin so that morphological and electrophysiological data could be obtained from the same cell. Before P15, injection of a single cell sometimes stained a cluster of neurons of similar morphology, probably as a result of dye coupling. The incidence of such clustering and the number of neurons within each cluster decreased with age. There was no obvious difference in electrophysiological properties between cells in clusters and age-matched, noncoupled neurons. From P5, the apical dendrites of neurons could easily be classified as "thick/tufted" or "slender/untufted." On average, the resting potential became more negative, and membrane time constant and input resistance decreased with age. Electrophysiological differences between the "thick/tufted" and "slender/untufted" cell types did not become apparent until the third postnatal week, after which the "thick/tufted" cells on average had lower input resistances and slightly faster time constants than "slender/untufted" cells. The current-voltage relations of the neurons became progressively more nonlinear during maturation, with both rapid inward rectification and time-dependent rectification or "sag" becoming more prominent. There were also changes in the amplitude and waveform of action potentials, which generally approached adult values by 3 weeks of age. Action potential threshold became more negative, both in absolute terms and relative to the resting membrane potential. Action potentials became larger in peak amplitude and of shorter duration, with both rise and fall times decreasing progressively during development.(ABSTRACT TRUNCATED AT 400 WORDS)

Hyperexcitability associated with localizable lesions in epileptic patients

Intracellular recordings from neurons were carried out in cortical slices obtained from tissue removed from patients suffering from intractable seizures. The patients were divided into two groups based on the presence or absence of an anatomical abnormality that could be imaged preoperatively. The lesion or its sorround was the presumptive epileptogenic area. The tissue removed from the patients without lesions was removed either for biopsy purposes or for access to epileptic tissue and was not considered epileptogenic. All neurons from patients without an imageable lesion, and some (19%) from patients with an imageable lesion, responded to orthodromic stimuli with a sequence of synaptic excitation followed by inhibition: these properties resembled those of normal rodent cortical slices. Different responses, classified as abnormal, were observed in 81% of the neurons in tissue specimens obtained near lesions. The most common was prolonged synaptic excitation with no noticeable inhibition, even at high stimulus strengths. In three resections, long latency all-or-none depolarization shifts were observed that resemble the classic paradoxical depolarization shift seen in in vivo extracellular recordings. Loss of specific inhibitory systems within the cortex may contribute in part to these abnormal responses.

Directional differences in excitability and margin of safety for propagation in sheep ventricular epicardial muscle.

Computer simulations and isolated tissue experiments were used to characterize the relation between excitability and margin of safety for propagation in anisotropic ventricular myocardium. Longitudinal, uniform transverse, and nonuniform transverse tissue directions were modeled in a one-dimensional Beeler-Reuter based cable. Stimulation threshold was smallest in the nonuniform transverse direction. The safety factor for propagation was determined in the model as the total axial charge that was available for depolarizing downstream tissue divided by the threshold charge that was just sufficient for continued propagation and was largest in the longitudinal direction. The strength-interval plot for the junction between simulated longitudinal and nonuniform transverse directions identified a range of stimulus strengths and intervals that resulted in nonuniform transverse but not longitudinal propagation. When high values of transverse resistance were used, higher stimulus strengths during premature stimulation resulted in longitudinal but not nonuniform transverse propagation. The experimental strength interval plots from 17 L-shaped preparations of isolated sheep epicardial muscles had similar characteristics. In nine additional L-shaped tissue experiments, changing extracellular K+ concentrations from 4 to 20 mM resulted in progressive membrane depolarization and conduction impairment in both directions. However, in eight of nine experiments, complete block occurred first in the transverse direction. In one experiment, block was simultaneous in both directions. We conclude that, under normal conditions, threshold requirements for active propagation are lower for transverse than for longitudinal propagation. In addition, when active membrane properties are impaired, the safety factor for propagation is larger in the direction along the longitudinal axis of the cells.

Mechanisms involved in the depolarization of cutaneous afferents produced by segmental and descending inputs in the cat spinal cord.

The relative contribution of specific and unspecific (potassium) components involved in the generation of primary afferent depolarization (PAD) of cutaneous fibres was analyzed in the spinal cord of the anesthetized cat. To this end we examined the correlation between the intraspinal threshold changes of single afferent fibres in the sural nerve produced by segmental and descending inputs and the negative DC potential shifts produced by these same stimuli at the site of excitability testing, the latter taken as indicators of the changes in extracellular concentration of potassium ions. Stimulation of the ipsilateral brain-stem reticular formation and of the contralateral red nucleus with 100-200 Hz trains reduced very effectively the intraspinal threshold of sural nerve fibres ending in the dorsal horn practically without producing any negative DC potential shifts at the site of excitability testing. However, negative DC potential shifts were produced more ventrally, in the intermediate nucleus and/or motor nucleus. Stimulation of the sural and superficial peroneus nerves with pulses at 2 Hz and strengths below 2 xT, also reduced the intraspinal threshold of single SU fibres without producing significant DC potential changes at the site of excitability testing. On the other hand, 100 Hz trains with strengths above 2 xT produced negative DC potential shifts and a proportional reduction of the intraspinal threshold of the SU fibres. The PAD of sural fibres produced by stimulation of rubro-spinal and reticulo-spinal fibres as well as by stimulation of sensory nerves with low frequency trains was unaffected or slightly increased, by i.v. injection of strychnine (0.2 mg/kg), but was readily abolished 5-10 min after the i.v. injection of picrotoxin (2 mg/kg). The results suggest that activation of reticulo-spinal and rubro-spinal fibres, as well as stimulation of cutaneous nerves with low frequencies and low strengths, produce PAD of cutaneous fibres involving activation of specific interneuronal pathways with interposed last-order GABAergic interneurons. The potassium component of the PAD produced by cutaneous fibres becomes dominant with high stimulus frequencies and strengths.

Non-cholinergic excitatory and inhibitory junction potentials in the circular smooth muscle of the guinea-pig ileum.

Intracellular micro-electrodes have been used to record evoked non-cholinergic junction potentials from the muscle layers of strips of guinea-pig ileum cut parallel to the longitudinal muscle. Transmural stimulation with single pulses, 0.6 ms duration produced inhibitory junction potentials (i.j.p.s) in the circular muscle layer. In the circular muscle layer, transmural stimulation with repetitive volleys (e.g. three pulses, 0.6 ms, 50 Hz delivered every 4 s) at low stimulus strengths (25-40 mA) produced non-cholinergic excitatory junction potentials (e.j.p.s) after an initial i.j.p. At higher stimulus strengths (greater than 40 mA) i.j.p.s occurred following each volley but were superimposed on a prolonged depolarization. Following repetitive volley stimulation every four seconds in the presence of apamin (0.25 microM), the i.j.p.s. were abolished and the non-cholinergic e.j.p.s clearly showed facilitation. At higher stimulus strengths (and at volley repetition rates of less than 0.1 Hz) volley stimulation now produced an apamin-resistant slow hyperpolarization followed by a distinct slow depolarization. Electrotonic potentials were readily recorded from the superficially located longitudinal muscle cells: in this muscle layer transmural stimulation produced small, slow changes in membrane potential. These results suggest that non-cholinergic excitatory and inhibitory nerve fibres primarily supply the circular rather than the longitudinal muscle layer in the guinea-pig ileum.

Characterization of a slow cholinergic post-synaptic potential recorded in vitro from rat hippocampal pyramidal cells.

Intracellular recording from CA1 pyramidal cells in the hippocampal slice preparation was used to compare the action of exogenously applied acetylcholine (ACh) and cholinomimetics to the effect of electrically stimulating sites in the slice known to contain cholinergic fibres. ACh depolarized pyramidal cells with an associated increase in input resistance, blocked a calcium-activated potassium conductance (GK(Ca], and blocked accommodation of action potential discharge. All of these actions were blocked by the muscarinic antagonist, atropine. Repetitive electrical stimulation of stratum (s.) oriens evoked a series of fast excitatory post-synaptic potentials (e.p.s.p.s) followed by an inhibitory post-synaptic potential. These potentials were followed by a slow e.p.s.p. that lasted 20-30 s. The slow e.p.s.p. was selectively enhanced by eserine and blocked by atropine. Ionophoretic application of ACh closely mimicked the time course of the slow e.p.s.p. The slow e.p.s.p. was blocked by tetrodotoxin and cadmium, indicating that it was dependent on propagated action potentials and on calcium. Considerably higher stimulus strengths were needed to elicit a slow e.p.s.p. than to elicit the earlier synaptic potentials. The size of the slow e.p.s.p. was markedly increased by repetitive stimulation. Stimulation of the alveus, s. oriens, s. pyramidale and fimbria all evoked a slow e.p.s.p., while stimulation of s. radiatum was relatively ineffective. The input resistance of the cell increased during the slow e.p.s.p. Hyperpolarizing the cell decreased the size of the slow e.p.s.p. and at membrane potentials of -70 mV or greater, little response was recorded. Stimulation of s. oriens blocked GK(Ca) and accommodation of action potential discharge. These effects, which could be seen in the absence of any change in membrane potential, were enhanced by eserine and blocked by atropine. The present electrophysiological results establish that CA1 pyramidal cells receive a cholinergic input and demonstrate that this input can dramatically alter the firing properties of these neurones for tens of seconds in the absence of any marked effect on membrane potential. Such an action contrasts with previously characterized synaptic potentials in this region of the brain.