The effects of focal epileptic activity on the somatosensory evoked potentials in the rat

Summary The cortical somatosensory evoked potential (SEP) of the rat, evoked by contralateral forepaw stimulation, consisted of early (P 1 and N 1) and late components (P 2 and N 2). Microelectrode recording yielded evoked unitary responses of short latencies in the range of the early components and responses of longer latencies in the range of P 2. During the development of focal epilepsy after topical application of penicillin, the late components of SEP were enhanced and the enhanced late negativity corresponded to a surface negative cortical spike. The prominent enlargement of later components was associated with prolonged, often recurrent discharges of longer latency unitary responses and with enlarged local field potentials. Early components of SEP remained relatively unaffected and so did unitary responses with short latencies.Epileptic spike-conditioned SEPs in the cuneate nucleus, thalamic sensory relay nucleus and sensory cortex were depressed from 100 ms (cuneate nucleus) to about 300 ms (thalamus and cortex) subsequent to spike discharge. Transmission in the cuneate nucleus was least affected. Thalamic and cortical early components of SEP had similar time courses of recovery, which differed markedly from that of cortical late components. Our findings suggest that two different neuronal activities generate different components of SEP and are differentially involved in the epileptic activities, which results in the different amplitude recovery following spontaneous epileptic spike discharges.This work was supported by the Deutsche Forschungsgemeinschaft (German Research Council)     

Central respiratory chemoreception

By definition central respiratory chemoreceptors (CRCs) are cells that are sensitive to changes in brain PCO₂ or pH and contribute to the stimulation of breathing elicited by hypercapnia or metabolic acidosis. CO₂ most likely works by lowering pH. The pertinent proton receptors have not been identified and may be ion channels. CRCs are probably neurons but may also include acid‐sensitive glia and vascular cells that communicate with neurons via paracrine mechanisms. Retrotrapezoid nucleus (RTN) neurons are the most completely characterized CRCs. Their high sensitivity to CO₂ in vivo presumably relies on their intrinsic acid sensitivity, excitatory inputs from the carotid bodies and brain regions such as raphe and hypothalamus, and facilitating influences from neighboring astrocytes. RTN neurons are necessary for the respiratory network to respond to CO₂ during the perinatal period and under anesthesia. In conscious adults, RTN neurons contribute to an unknown degree to the pH‐dependent regulation of breathing rate, inspiratory, and expiratory activity. The abnormal prenatal development of RTN neurons probably contributes to the congenital central hypoventilation syndrome. Other CRCs presumably exist, but the supportive evidence is less complete. The proposed locations of these CRCs are the medullary raphe, the nucleus tractus solitarius, the ventrolateral medulla, the fastigial nucleus, and the hypothalamus. Several wake‐promoting systems (serotonergic and catecholaminergic neurons, orexinergic neurons) are also putative CRCs. Their contribution to central respiratory chemoreception may be behavior dependent or vary according to the state of vigilance. J. Comp. Neurol. 518:3883–3906, 2010. © 2010 Wiley‐Liss, Inc.     

Responses of ganglion cells to repetitive electrical stimulation of the retina

Retinal ganglion cells (RGCs) can be activated electrically either directly or indirectly (via the retinal neural network). Previous studies have shown that RGCs can follow high stimulus rates (> or = 200 pulses s(-1)) when directly activated. In the present study, we investigated how well RGCs can follow repetitive stimulation of the neural network. We studied the responses (spike activity) of RGCs in isolated rabbit retina to stimulation with paired pulses applied at different interpulse intervals and trains of pulses applied at different frequencies. We found that the response amplitude of a RGC to a current pulse applied soon (< or = 400 ms) after a preceding current pulse is diminished. This depression in response amplitude became greater as the interval between pulses became shorter. At an interpulse interval of 15 ms (shortest tested), the response amplitude to the second current pulse was reduced on average 94%. When a train of ten stimulus pulses was applied, further depression was observed, particularly at high stimulation frequencies. The depression with each successive pulse was relatively moderate compared to the depression to the second pulse. The results of this study have implications for the design of electrical stimulation strategies in a retinal prosthesis.     

The effects of QX-314 on medullary respiratory neurones

The synaptic and current-evoked responses of respiratory neurones located in the nucleus of the tractus solitarius, the para- and retroambigual regions and the nucleus ambiguus, were examined after voltage-dependent sodium currents were blocked by intracellular application of the quaternary lidocaine derivative QX-314. (1) QX-314 abolished orthodromically and antidromically evoked action potential discharge. Only antidromic action potentials recovered during negative DC current injection. (2) QX-314 did not alter the amplitude or duration of small and short excitatory and inhibitory postsynaptic potentials evoked by vagus or superior laryngeal nerve stimulation. Larger and longer waves of spontaneous membrane depolarizations, however, were slightly diminished. (3) The repetitive discharge evoked by depolarizing current pulses was blocked by QX-314. Positive current pulses produced less membrane depolarization than under control and often evoked only a single action potential at the beginning of the pulse, indicating that QX-314 interferes with the processes responsible for repetitive firing. (4) When fast spike discharges were completely blocked, positive current pulses occasionally evoked depolarizing 'spikes' and potentials which were followed by a hyperpolarization. We conclude that a noninactivating sodium inward current and calcium currents contribute to the electroresponsiveness of respiratory neurones.     

The GABAB receptor antagonist, CGP-35348, inhibits paired-pulse disinhibition in the rat dentate gyrus in vivo.

Extracellular field potentials were recorded from the dentate gyrus of adult rats during electrical stimulation of the angular bundle in vivo. Paired pulses produced inhibition of the second population spike (PS2) at 25 ms, and potentiation at inter-stimulus intervals from 50 to 200 ms. The GABAB receptor antagonist, CGP 35348, reduced the amplitude of PS2 at each of these inter-stimulus intervals while producing no effect on the first population spike of the pair (PS1). Under control conditions, the duration of the second population EPSP (pEPSP2) was increased relative to the first at inter-stimulus intervals from 100 to 400 ms, and CGP 35348 reduced these durations to baseline levels. These results demonstrate that GABAB receptors modulate synaptic inhibition in vivo.     

Effects of pentobarbital on respiratory functional dynamics in chronically instrumented guinea pigs

Respiratory effects of sodium pentobarbital (35 mg/kg; IP) were studied in guinea pigs chronically instrumented to permit concurrent recordings of bulbar respiratory-related units (RRUs), diaphragmatic electromyogram (DEMG), and electrocorticogram (ECoG). RRU activities were recorded from either the B?tzinger Complex (BOT; expiratory) or Nucleus para-Ambiguus (NpA; inspiratory). Pentobarbital-induced changes in respiratory-related activities were evaluated before, throughout the course of, and during recovery from, anesthesia. The most notable development following pentobarbital was a state of progressive bradypnea which was accompanied by a variety of complex changes in the amplitude and temporal attributes of RRU, DEMG and ECoG activities. As anesthetic effects progressed, the activity profiles of both BOT and NpA units underwent striking transformations from a behavioral and state-dependent wakefulness pattern to an activity profile characterized by i) a significantly augmented RRU cycle duration, burst duration and spike frequency; and, ii) an alteration to the pattern of within-burst spike frequency modulation. Along with changes in RRU activity, pentobarbital also produced a marked attenuation of the amplitudes of diaphragmatic activity as well as a discrete, time-dependent alteration in the amplitude and spectral characters of ECoG activities. Differences in BOT and NpA unit responses to alveolar CO2 loading (ramp; 2% and 5%) across wakefulness and anesthesia states were also considerable. In addition to a depressed responsiveness to CO2, the temporal attributes of BOT and NpA activity profiles also indicated an asymmetrical change under pentobarbital anesthesia. Taken together, these findings indicate that pentobarbital causes not only a fundamental alteration in bulbar rhythmogenic mechanisms, but also a differential influence on bulbar respiratory system components that are involved in the definition of the shape and the amplitude of central respiratory drive. In conclusion, this study offers, for the first time, direct evidence from physiologically and structurally intact preparations that the functional dynamics of respiratory system components are profoundly altered during pentobarbital anesthesia.     

Phox2b-expressing neurons of the parafacial region regulate breathing rate, inspiration, and expiration in conscious rats

The retrotrapezoid nucleus contains Phox2b-expressing glutamatergic neurons (RTN-Phox2b neurons) that regulate breathing in a CO?-dependent manner. Here we use channelrhodopsin-based optogenetics to explore how these neurons control breathing in conscious and anesthetized adult rats. Respiratory entrainment (pacing) of breathing frequency (fR) was produced over 57% (anesthetized) and 28% (conscious) of the natural frequency range by burst activation of RTN-Phox2b neurons (3-8 × 0.5-20 ms pulses at 20 Hz). In conscious rats, pacing under normocapnic conditions increased tidal volume (V(T)) and each inspiration was preceded by active expiration, denoting abdominal muscle contraction. During long-term pacing V(T) returned to prestimulation levels, suggesting that central chemoreceptors such as RTN-Phox2b neurons regulate V(T) partly independently of their effect on fR. Randomly applied light trains reset the respiratory rhythm and shortened the expiratory phase when the stimulus coincided with late-inspiration or early-expiration. Importantly, continuous (20 Hz) photostimulation of the RTN-Phox2b neurons and a saturating CO? concentration produced similar effects on breathing that were much larger than those elicited by phasic RTN stimulation. In sum, consistent with their anatomical projections, RTN-Phox2b neurons regulate lung ventilation by controlling breathing frequency, inspiration, and active expiration. Adult RTN-Phox2b neurons can entrain the respiratory rhythm if their discharge is artificially synchronized, but continuous activation of these neurons is much more effective at increasing lung ventilation. These results suggest that RTN-Phox2b neurons are no longer rhythmogenic in adulthood and that their average discharge rate may be far more important than their discharge pattern in driving lung ventilation.     

Intracellular responses of the rat anteroventral cochlear nucleus to intracochlear electrical stimulation

The anteroventral cochlear nucleus (AVCN) is the first central processing site for acoustic information. The influence and extent of convergent auditory nerve input to AVCN neurons was investigated using brief (<0.2 ms) intracochlear electrical activation of spiral ganglion cells. In 40 neurons recorded in vivo, the major intracellular response to stimulation was an excitatory postsynaptic potential (EPSP) with short latency (∼1 ms) and fast rise time (<1 ms). Graduated EPSP amplitude increases were also seen with increasing stimulation strength resulting in spike generation. Hyperpolarization followed excitation in most neurons, its extent distinguished three response types: Type I showed no hyperpolarization; Type II and Type III displayed short (<10 ms) and long (>19 ms) duration hyperpolarization, respectively. Hyperpolarization was attributed to an inhibitory postsynaptic potential (IPSP) in addition to spike after hyperpolarization. Neurobiotin filling identified Type I and II neurons as stellate and Type III as bushy cells. These results suggests that AVCN neurons receive direct, possibly convergent, excitatory input from auditory nerves emanating from spiral ganglion cells with hyperpolarization resulting from polysynaptic inhibitory input.     

Stimulus parameters affecting paired-pulse depression of dentate granule cell field potentials. I. Stimulus intensity

Paired pulse stimulation of the perforant path provides a measure of inhibition of dentate granule cell field potentials that is reflected in the depression of the second (test) population spike (PS) relative to the first (conditioning) PS. The assumption that the strength of paired pulse depression is dependent upon the amplitude of the conditioning PS was investigated by increasing the stimulus intensity of both pulses (5–100% of maximum, Experiment 1), or by increasing the stimulus intensity of the conditioning pulse (5–100%) while maintaining a constant stimulus intensity of the test pulse (50%, Experiment 2). In both experiments, the threshold for early paired pulse depression (20 ms interpulse interval, IPI) was reached with moderate stimulation (30–40% of maximum). Above threshold, the test PS was depressed to a relatively constant amplitude in Experiment 1, in contrast to a nearly linear decrease observed in Experiment 2 with increasing stimulus intensity. This difference most likely reflects the lower stimulus intensity of the test pulse, relative to the conditioning pulse, in the second study, thereby allowing the increasing strength of early paired pulse depression to be detected more easily. The threshold for late paired pulse depression was reached near (20%, Experiment 1) or below (5%, Experiment 2) the PS threshold of dentate granule cells, and a paradoxical decrease in late paired pulse depression was detected with maximal stimulation in both studies. Together, these results suggest that early paired pulse depression exhibits a strong dependence upon the amplitude of the conditioning PS, whereas late paired pulse depression is marginally affected by the conditioning PS amplitude and is influenced by additional processes at both extremes of the stimulus intensity continuum.     

State-dependent alteration of respiratory cycle timing by stimulation of the central nucleus of the amygdala

The effect of electrical stimulation of the amygdaloid central nucleus (ACE) on respiration was studied in unanesthetized, unrestrained cats during sleep-waking states. Single 0.5-ms 500-microA constant-current pulses delivered to the ACE at various points on the respiratory cycle, produced a transient inspiratory effort which summated with ongoing inspiratory activity and reduced inspiratory time. Stimulus pulses delivered during the expiratory phase resulted in an earlier shift to inspiration. Repetitive single pulse stimuli delivered to the ACE at a rate slightly faster than the spontaneous respiratory cycle during the alert state, were capable of 'entraining' respiration at the stimulus frequency. This entrainment disappeared in quiet sleep. Atropine, however, which produced synchronous high voltage slow waves and 12-14-Hz EEG spindle activity in the alert cat, did not impair this entrainment. Short (300-500 ms) 100-Hz trains of 0.5-ms pulses to the ACE produced rapid onset, sustained inspiration and a rise in blood pressure in the alert animal. During quiet sleep the response was attenuated but qualitatively similar, and also aroused the animal. Single pulse stimuli, however, were not associated with cardiovascular changes or generalized arousal. These results suggest that the ACE contributes to excitation of the inspiratory cycle, possibly through the large projection of this nucleus to the parabrachial pons.     

Stimulus parameters affecting paired-pulse depression of dentate granule cell field potentials. II. Low-frequency stimulation

Low frequency (1 Hz) stimulation of the perforant path produces a depression in the population spike (PS) of dentate granule cell field potentials and also may affect the strength of paired pulse depression. The effects of 1 Hz stimulation (30 s train) on paired pulse depression (20 and 200 ms interpulse intervals, IPI) were evaluated in the unanesthetized rat under two conditions: (i) when the stimulus intensity of both pulses was increased simultaneously (5–100%); and (ii) when the stimulus intensity of the first (conditioning) pulse was increased (5–100%), while the stimulus intensity of the second (test) pulse was held constant (50%). The test PS amplitude was predicted based upon either the conditioning PS amplitude at the end of the 1 Hz train or upon the additive effects of paired pulse depression and 1 Hz stimulation. These predicted values then were assessed for the best fit to observed values following 1 Hz trains. Under both stimulus conditions, the 1 Hz depression in the conditioning PS amplitude exhibited characteristics that were identical to late paired pulse depression recorded before the train. A decrease in the test PS amplitude also was observed following 1 Hz stimulation at the 20 and 200 ms IPIs. The best fit to observed values of the test PS at the end of 1 Hz trains was provided by estimates based upon the additive effects of 1 Hz stimulation and paired pulse depression. These results indicate that the strenght of paired pulse depression in the unanesthetized rat is unchanged following 1 Hz stimulation, and further, that the 1 Hz depression in dentate granule cell field potentials most likely reflects the cumulative influence of late paired pulse depression.     

Acoustic transmission in the dentate nucleus: I. Patterns of activity to click and hiss; II. Changes in activity and excitability after conditioning

Recordings were made from 95 units of the dentate nucleus of naive cats to determine if patterns of response to 70 dB clicks could be distinguished from those to another acoustic stimulus (a hiss) of approximately equal sound pressure level. Further studies of an additional 309 units were conducted to determine if unit excitability and the response to clicks changed after Pavlovian conditioning in which blink responses were elicited by the clicks as conditioned stimuli. Over 50% of units tested before conditioning responded to click or hiss with increased activity, and 8% responded in the first 4–8 ms after the onset of the rapidly rising click. Cross-correlation of the respective 160 ms poststimulus histogram averages of mean activity showed dissimilar patterns of response to clicks and hisses (Pearson product-moment correlation coefficient+0.02). Thus the averaged population responses distinguished these stimuli. In addition, individual cells were found in each behavioral state that responded selectively to either click or hiss. After conditioning with click as the conditioned stimulus, the number of units responding in the first 4–8 ms to click increased to 23%. The mean magnitude of activity 4–8 ms after presenting the click increased after conditioning but not after sensitization produced by backward pairing of the stimuli used for conditioning. After backward pairing only 6% of the units responded in the first 4–8 ms to click. The changes in activity after conditioning were accompanied by increases in neural excitability to intracellularly applied depolarizing current. In contrast with the changes in activity, the increases in neural excitability were also found after backward pairing. We conclude that short as well as long latency acoustic transmissions to click change in the dentate nucleus after conditioning, that changes in response to click are expressed in 4–8 ms responsive cells, and that many of these cells have different patterns of spike activity in response to click and hiss. The findings support the hypothesis that the dentate nucleus can play a significant role in short as well as long latency, adaptive acoustic transmission that can enhance the response to an acoustic signal used as a Pavlovian conditioned stimulus.     

Reactions of neurons of the reticular and ventral anterior thalamic nuclei to electrical stimulation of the centrum medianum of the thalamus

Responses of 145 reticular (R) and 158 ventral anterior (VA) thalamic neurons to electrical stimulation of centrum medianum (CM) were studied in cats anaesthetized with thiopental sodium (30-40 mg/kg intraperitoneally) and immobilized with d-tubocurarine (1 mg/kg). 4.1% of R and 4.4% of VA neurons under study responded to CM stimulation by antidromic spike (latency 0.3-2.0 ms). The conduction velocity of antidromic excitation in axons of those neurons was found to be 1.7-7.6 m/s. There were neurons which responded by antidromic spike to the other thalamic nuclei stimulation as well as to CM. This fact is the electrophysiological proof of the axonal branching in these neurons. 53.8% of R and 46.9% of VA neurons responded to CM stimulation with orthodromic excitation. Two groups of cells were separated among neurons excited orthodromically. The first group neurons responded to CM stimulation by discharges composed of 6-12 spikes with frequency of 130-640 per second. The neurons of the second group generated a single spike. Inhibitory reactions were noticed only in 0.7% of R and in 4.4% of VA neurons. It is shown that afferent impulses from relay nuclei, lateral posterior nucleus and motor cortex converged to some R and VA neurons responding to CM.     

Inhibitory synaptic interactions between cochlear nuclei: evidence from an in vitro whole brain study.

Using guinea-pig isolated whole brain preparation in vitro, synaptic responses to electrical stimulation of auditory nerves were examined in intracellularly recorded and stained neurons of posteroventral and dorsal divisions of the cochlear nucleus. Stimulation of the contralateral auditory nerve evoked exclusively IPSPs in 70% of neurons, with amplitude of 2.3+/-1.2mV. Neurons of all major cell types were inhibited from the contralateral side. In the majority of responding cells (78%) IPSPs were induced at latencies of 3-9 ms suggesting di- and trisynaptic connections from contralateral auditory afferents or, respectively, mono- and disynaptic connections from the contralateral cochlear nucleus. Few cells responded with long-latency IPSPs (13.5-23ms), indicating involvement of polysynaptic pathways. These data demonstrate the existence of functional, direct and indirect inhibitory connections between the cochlear nuclei.     

In vivo intracellular correlates of hippocampal formation theta-on and theta-off cells.

Using urethane-anesthetized rat, intracellular recordings were made in hippocampal formation cells classified according to previously established criteria as either theta-on or theta-off, in order to further define the electrophysiological characteristics of these cells. Four cells classified as phasic theta-off cells had short duration spikes (less than 1 ms), high input resistances (54-61 M omega) and large fast afterhyperpolarizations (6-10 mV), thus sharing some of the properties of identified hippocampal interneurons. Phasic theta-off cells also exhibited rhythmic membrane potential oscillations (MPOs) ranging from 4 to 10 mV in amplitude during the simultaneous occurrence of extracellular theta field activity, but not during the occurrence of large amplitude irregular field activity (LIA). The MPOs of phasic theta-off cells were the same frequency as and were highly coherent with the extracellular theta field activity. In all four phasic theta-off cells the positive peak of the MPO was in phase with the positive peak of the local theta field activity. At the onset of extracellular theta field activity above 4-5 Hz, the membrane potentials of phasic theta-off cells showed a 5-10-mV hyperpolarizing shift, accompanied by MPOs without spike discharges. As theta frequency slowed down there was a return to baseline membrane potential levels and spike discharges occurred near the positive peak of the MPOs. The seven cells classified as phasic theta-on had longer duration spikes (greater than 1 ms), lower input resistances (22-36 M omega) and small (approx. 1.0 mV) fast afterhyperpolarizations, thus sharing some of the properties of hippocampal projection cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of D890 on membrane properties of neocortical neurons

D890, a derivative of the Ca²⁺ channel antagonist D600, was intracellularly applied from conventional microelectrodes into pyramidal neurons of neocortical slices. The effects of D890 were ascertained by evaluating alterations in membrane properties following drug administration and by comparing these neurons to untreated controls. The amplitude of action potentials (APs) evoked by depolarizing current pulses was attenuated by up to 30% within about 15 min after impalement with D890-containing electrodes. AP rate of rise was reduced by up to 80% and duration was increased. These effects were dependent upon the rate of stimulation. When depolarizing pulses were delivered at low rates of stimulation (e.g. 0.1 Hz), the overshoot of evoked APs declined by about 10%. At higher frequencies (2Hz) the AP overshoot decreased by up to 90%. These effects were mostly reversible on decreasing the frequency of stimulation. A half maximal effect was attained at about 1 Hz, when APs of control neurons were unaltered. In neurons impaled with D890-containing electrodes, depolarizing current pulses delivered in the presence of tetraethylammonium (TEA) and tetrodotoxin elicited high threshold calcium spikes which had a duration between 20 and 200 ms. In the early phase of D890 application, the duration of Ca²⁺ spikes decreased in a reversible frequency-dependent manner; after prolonged application, however, the recovery was incomplete. On the average, Ca²⁺ spike amplitude and duration decreased by 20% and 50%, respectively, suggesting that D890 usually produces an incomplete blockade of the underlying CA current. The duration of the slow envelope of orthodromically evoked epileptiform paroxysmal depolarizing shifts (DSs), induced by bath application of 10⁻⁵ M bicuculline, was frequency dependent and consistently increased from about 20 ms to 150 ms (half amplitude width) at frequencies above 0.5 Hz. In the presence of D890, the action potentials superimposed on the slow envelope of the DS were attenuated, but neither the amplitude nor the frequency-dependent progressive prolongation of the DS was altered. Application of TEA in the presence of bicuculline (10⁻⁵ M) increased the amplitude and duration of the DS in neurons impaled with D890-containing electrodes. Under these conditions, the durations of DSs evoked by low frequency orthodromic stimulation (0.5Hz) were still progressively prolonged, while, in the same neuron, directly evoked Ca²⁺ spikes progressively decreased in amplitude and duration. During DSs, the membrane potential depolarized to levels beyond those required for directly eliciting high threshold Ca²⁺ spikes, however, a Ca²⁺-spike component was not obvious during the DS. A high conductance state of the membrane at the peak of the DS may limit Ca²⁺ spike electrogenesis. The results suggest that D890 affects fast Na⁺ currents and the conventional Ca²⁺ conductance underlying the Ca²⁺ spike. The absence of effects of D890 on the DS slow envelope suggests that Ca²⁺ conductances do not make a large contribution to the latter in the neurons studied, or that Ca²⁺ flows through channels with different pharmacological properties during the DS and the Ca²⁺ spike.     

Central drive on Renshaw cells coupled with phrenic motoneurons

In anesthesized spontaneously breathing cats (C4–C5 deafferentation), recurrent inhibition of phrenic motoneurons was analyzed by studying either recurrent IPSPs in phrenic motoneurons, or Renshaw cell discharges evoked by C5 phrenic nerve stimulation. Of 90 intracellularly recorded phrenic motoneurons, 7 motoneurons showed evoked recurrent IPSPs with stimulation of C5 phrenic axons subthreshold for eliciting antidromic activation of the motoneuron from which intracellular recording was done. These IPSPs could be reversed by imposed hyperpolarization of the motoneuron, and were of greater amplitude during inspiration than during expiration. Within the phrenic nucleus, interneurons were classified as Renshaw cells if they responded to C5 phrenic axon stimulation with a typical high frequency burst of potentials. Reactivity of these Renshaw cells was related to the respiratory cycle, number of spikes in the burst being greater during inspiration than during expiration. Injection of a nicotinic cholinergic blocker (mecamylamine) decreased responses of Renshaw cells but the respiratory modulation was still present. Some Renshaw cells (18/33) were spontaneously active during inspiration. Their activity was generally maximal during the last third of inspiration. Since: (1) spontaneous activity of Renshaw cells is related to the respiratory drive; (2) persists after C7 spinal transection and after mecamylamine poisoning of the axonal recurrent pathway; and (3) might appear before sustained phrenic activity, the assumption of a central respiratory drive impinging on the Renshaw cells has to be retained.     

Assessment of trigeminal small-fiber function: brain and reflex responses evoked by CO2-laser stimulation

Laser pulses selectively excite mechano-thermal nociceptors and evoke brain potentials that may reveal small-fiber dysfunction. We applied CO2-laser pulses to the perioral and supraorbital regions and recorded the scalp laser-evoked potentials (LEPs) and reflex responses in the orbicularis oculi, masticatory, and neck muscles in 30 controls and 10 patients with facial sensory disturbances. Low-intensity pulses readily evoked scalp potentials consisting of a negative component with a latency of 165 ms followed by a positive component at 250 ms. In vertex recordings, the amplitude of LEPs exceeded 30 microV. Although only high-intensity pulses evoked reflex responses, some subjects showed--even to low-intensity pulses--an orbicularis oculi (blink-like) response that markedly contaminated the scalp recording. Scalp LEPs were abnormal in patients with hypalgesia and normal trigeminal reflexes and normal in patients with normal pain sensitivity and abnormal trigeminal reflexes. Possibly because of the high receptor density in this area and the short conduction distance, laser stimulation of the trigeminal territory yields low-threshold and large LEPs, which are useful for detecting dysfunction in peripheral and central pain pathways.     

The transient potassium current, the A-current, is involved in spike frequency adaptation in rat amygdala neurons

The possible functional roles of the transient K⁺ current, I_A, in basolateral amygdala (BLA) neurons were studied using a rat brain slice preparation and conventional intracellular recording techniques. Conditioning depolarization, which inactivates I_A slowed the action potential repolarization while conditioning hyperpolarization accelarated the action potential repolarization. 4-Aminopyridine (4-AP, 100 μM), a specific I_A antagonist, also caused a clear delay in spike repolarization similar to the effect of conditioning depolarization suggesting that I_A is involved in the action potential repolarization.

When BLA neurons were excited by injecting long depolarizing current pulses (500 ms), they responded with an initial rapid discharge of action potentials which slowed or accommodated; an afterhyperpolarization (AHP) followed the depolarizing current pulses. Superfusion of 4-AP (100 μM) blocked accommodation resulting in an increase in action potential discharge in 74% (32 out of 43) neurons tested. The remaining 11 cells responded with an increased frequency of discharge of the first few action potentials. Unlike the effect of cadmium (Cd²⁺, 100 μM), a calcium channel blocker, 4-AP did not reduce the AHP. In the presence of norepinephrine (NE, 10 μM), a neurotransmitter which has been shown to block calcium-activated potassuim conductance, 4-AP caused a further increase in the number and frequency of action potential discharge. In addition, in BLA neurons, spontaneous interictal and ictal-like events were observed at low and high concentrations of 4-AP, respectively. We conclude that I_A is involved in the action potential repolarization as well as spike frequency adaptation in BLA neurons and that these actionsmay contribute to the convulsant effect of 4-AP     

Gaze shifts evoked by electrical stimulation of the superior colliculus in the head-unrestrained cat. I. Effect of the locus and of the parameters of stimulation

Several studies have suggested that the pattern of neuronal activity in the superior colliculus (SC) interacts with the well-known topographical coding of saccades (motor map). To further describe this interaction, we recorded gaze saccades evoked by electrical microstimulation of SC deeper layers in the head-unrestrained cat and systematically varied the collicular locus (25 sites) and parameters (intensity, frequency) of the stimulation. Long stimulation trains were used to avoid saccade truncation. We found that the direction and amplitude of evoked gaze shifts were related to the stimulation locus, describing a gaze shift map. For 18 out of 20 sites the amplitude, but not the direction, also strongly depended on stimulation strength. Indeed, gaze amplitude continuously increased when raising current intensity up to several times the threshold value T (the largest intensity tested was 6 x T), whereas varying pulse frequency from 150 to 750 pulses per second (p.p.s.) revealed an optimal frequency range (300 and 500 p.p.s.) eliciting the largest gaze shifts. Moreover, the intensity effect on amplitude increased in an orderly fashion with the rostro-caudal stimulation locus. Gaze shift amplitude was not related to the number of delivered stimulation pulses. Concerning movement initiation, increasing either intensity or frequency led to an exponential decrease in gaze latency until minimal values near 30 ms were reached, but the number of pulses delivered during the corresponding latency period remained constant within a 300-500 p.p.s. frequency range. These findings indicate that the pattern of collicular discharge evoked by electrical stimulation strongly interacts with the gaze shift map and provide evidence for a summation of collicular activities by downstream premotor neurons.