The signal transduction pathway for the dopamine D1 receptor in the guinea-pig cochlea

Dopamine released from lateral efferent fibers modulates the activity of the auditory nerve, but the signaling mechanism by which this is mediated is not known. The present study investigated the signal transduction pathway for the dopamine D1 receptor in the guinea-pig cochlea. D1 receptor immunolabeling was localized to the spiral ganglia neurons and at the base of the inner hair cells. Western immunoblotting on whole cochlear preparations revealed positive bands for the D1 receptor and for dopamine and the cyclic AMP-regulated phosphoprotein. The amplitude of the compound action potential was enhanced in the presence of the D1 receptor agonist, SKF 38393, an effect that was abolished by H89, a protein kinase A inhibitor. Conversely, SKF 83566, a D1 receptor antagonist decreased the amplitude of compound action potential, while forskolin, a protein kinase A activator prevented this effect. Furthermore, it was found that the level of glutamate receptor 1 phosphorylation at the protein kinase A site (Ser845) was increased by the D1 agonist, but decreased by D1 antagonist. Our results provide evidence that the D1 receptor is localized in the spiral ganglion neurons as well as the nerve endings under the inner hair cells and they can modulate auditory nerve function. One signal transduction pathway of D1 receptor in the auditory nerve is via protein kinase A-mediated glutamate receptor 1 phosphorylation.     

Decremental Conduction,in Normal Human Nerves Subjected to Ischemia?

The effect of ischemia on the maximal orthodromic sensory and motor nerve conduction was studied in the digit 1-elbow segment of the median nerve in 24 normal subjects. Action potentials were recorded at 2, 3 or 4 sites along the nerve. The latency of the potentials increased as a function of the duration of ischemia and of the distance from the point of stimulation. The earliest indication of an impaired nerve function was a decrease in the sensory action potential amplitude. During ischemia the length of the nerve segment, through which the potential was propagated, gradually became shortened. This was seen in sensory as well as in motor nerves. The sensory threshold to electrical stimuli (digit 3) had a two-phasic course: During 15 min of ischemia it was almost stationary despite a severe reduction of the conduction velocity and of the potential amplitude. Then a rapid increase took place, coincicling with the extinction of the potential recorded at the elbow just below the occlucling cuff. The conduction parameters were normalized shortly after reestablishment of the circulation in the arm. The results indicate that action potentials become conducted with decrement during ischemia.     

Field potential response changes in the rabbit olfactory bulb accompany behavioral habituation during the repeated presentation of unreinforced odors

Summary Experiments were performed on waking rabbits to investigate the changes in both sniffing behavior and local field potential responses in the olfactory bulb during repeated exposure to unreinforced odors. Six rabbits were each implanted with 2 pairs of electrodes for differential recording of the bulbar extracellular field potential. Each animal was given 3 sequential sessions to each of 2 separate odors on 6 consecutive days, while monitoring the bulbar field potential activity and sniffing behavior. Behavioral sniffing responses exhibited rapid within-session decrement in amplitude and long term decrement across sessions. The within-session decrement showed spontaneous recovery between sessions. Both decremental changes in sniffing behavior were accompanied by changes in the bulbar field potential responses. The responses to novel odors were characterized by a reduction in amplitude of high frequency activity (40–80 Hz) and a corresponding increase in amplitude of low frequency activity (15–25 Hz). The high frequency component of the responses showed an initial increase in frequency to a novel odor on the first 3 presentations followed by a rapid decrease in frequency on subsequent trials in the first session which stabilized thereafter. No change in frequency or relative amplitude was observed for the low frequency component. The absolute difference between the odor evoked activity and the preceeding control activity measured on each trial showed a significant decrement across sessions with no evidence for spontaneous recovery. The results demonstrate that olfactory bulb responses to novel unreinforced odors show both rapid and long-term changes which parallel changes in sniffing behavior. These changes, which have been predicted by a theoretical model of the olfactory bulb (Freeman 1979a, b), are postulated to reduce the spatial specificity of the response pattern to unreinforced odors.     

Action potentials and membrane currents in the human node of Ranvier

Action potentials and membrane currents were recorded in single human myelinated nerve fibres under current- and voltage-clamp conditions at room temperature. Nerve material was obtained from patients undergoing nerve graft operations. Successful recordings were made in 11 nerve fibres. In Ringer's solution, large transient Na currents were recorded, which could be blocked completely with tetrodotoxin. Partial block of these currents with 3 nM tetrodotoxin was used to reduce the voltage-clamp error due to series resistance. Outward K currents were very small in intact nerve fibres, but had a large amplitude in fibres showing signs of paranodal demyelination. In isotonic KCl, the K current could be separated into three components: two fast components (K_f1 and K_f2) and one slow component (K_s). Time constants and steady-state activation and inactivation of Na permeability and of fast and slow K conductance were measured within the potential range of –145 mV to +115 mV. From these parameters, the corresponding rate constants were calculated and a mathematical model based on the Frankenhaeuser-Huxley equations was derived. Calculated action potentials closely matched those recorded. Single calculated action potentials were little affected by removing the fast or slow K conductance, but the slow K conductance was required to limit the repetitive response of the model to prolonged stimulating currents.     

Backfiring of the isolated rat phrenic nerve does not collide with impulse propagation following repetitive nerve stimulation at 1–50 Hz

Acetylcholinesterase inhibition with neostigmine in the isolated rat phrenic nerve-hemidiaphragm preparation induced axonal backfiring and repetitive compound muscle action potentials following single nerve stimulation. The duration of backfiring and the repetitive compound muscle action potentials did not exceed 55 ms. With repetitive nerve stimulation at frequencies ranging from 1 to 50 Hz, backfiring was present only with the first stimulus and the amplitude of the second compound muscle action potential was maximally reduced, while the subsequent responses recovered gradually. However, the amplitudes of the concommitant antidromic nerve action potentials remained unchanged during the entire train of stimulation. Lack of nerve action potential amplitude changes and the short duration of backfiring of the first nerve action potential exclude a collision phenomenon of backfiring with the nerve action potential induced by the second stimulus. Moreover, the duration of the repetitive compound muscle action potentials did not exceed the duration of backfiring. Therefore, the prolongation of the muscle membrane refractory period by reexcitation following backfiring cannot explain the decrement of the second compound muscle action potential.     

Sensory interaction: Evoked potential observations in man

Summary Polysensory averaged evoked potentials were evaluated as a function of the interval between a flash and a click which followed it at intervals ranging from 20—120 msec. This was done in two experimental series in each of which the subject's task was to respond manually to the flash. One of these required a choice reaction, namely, withholding of motor response when click was occasionally presented alone.Both evoked potential amplitude and reaction times showed a linear relationship to interstimulus interval; at shorter intervals, the amplitude of the polysensory evoked response was higher and reaction times were faster.Topographical analysis indicated that the electrophysiological findings were more consistently obtained in recordings from transverse bipolar leads than from pairs in the anterior-posterior plane. Responses recorded from the left motor region (contralateral to the arm employed in the manual response) showed the effect more consistently than did those from the homotopic recording site on the right motor cortex.Ratios were calculated between the amplitude of the obtained polysensory evoked responses and a theoretical one expected by algebraic addition of the responses to the two stimuli as presented singly. It was found that ratios were consistently higher for the left motor region when compared to the right. Only at the left was there a reliable relationship between interstimulus interval and the calculated ratio, with values greater than one at short interstimulus intervals and a linear decrement in the ratio value as interstimulus interval lengthened.Supported by NASA grant NsG 215-62     

STIMULUS REPETITION RATE FACTORS WHICH INFLUENCE THE AUDITORY EVOKED POTENTIAL IN MAN

The slow component of the auditory evoked potential in man was investigated under various conditions which produced an increase in stimulus repetition rate. The left ear received a 1000 Hz tone once each 5 sec. Intervening stimuli, also of 1000 Hz, were presented to (1) the right ear, (2) both ears, and (3) the left ear. Their relative influence on response amplitude to periodic left ear stimulation was evaluated. The results indicated that: (1) intervening right ear stimulation reduced significantly response amplitude to left ear stimulation; (2) presenting the intervening stimuli to both ears simultaneously caused no further decrement in response amplitude; (3) presenting the intervening stimuli to the left ear alone brought about a further and significant decrease in response amplitude to left ear stimulation. These findings imply that habituation of the auditory evoked potential is greatest when the same pattern of neural activity is repeatedly initiated. When the intervening stimuli elicit a different pattern of neural excitation, habituation is less, even though stimulation rate remains unchanged.     

膈神经传导以及膈运动诱发电位对呼吸功能障碍评价的初步探讨

目的：初步探讨膈神经传导（ＰＮＣ）及膈运动诱发电位（ＭＥＰ）对评价各种呼吸功能障碍的价值。方法：对３４例病人（各种神经肌肉疾病１９例、呼吸系统疾病１５例）在胸锁乳突肌后缘中点用电刺激膈神经,于第７—８肋间和剑突处记录膈肌复合动作电位;用磁圈置于对侧头皮进行刺激,在深吸气状态下记录膈ＭＥＰ。结果：肌病患者的ＰＮＣ均正常;格林巴利综合征、重症肌无力危象以及遗传性运动感觉神经病者的ＰＮＣ均异常,动态观察结果均表现为ＰＮＣ与呼吸功能障碍显著相关;７例睡眠呼吸暂停综合征中４例ＰＮＣ异常;３例慢性阻塞性肺病有２例主要表现为膈肌电位波幅低;憋气、平卧时呼吸困难者患者５例中仅１例表现为单侧膈肌电位波幅低;５例作ＭＥＰ的睡眠呼吸暂停综合征者３例异常、３例慢性阻塞性肺病者的隔ＭＥＰ均正常。结论：ＰＮＣ不仅可客观地评价神经肌肉性呼吸功能障碍、预示疾病过程,而且还可为呼吸系统病变所致呼吸功能障碍提供膈肌功能障碍的其它信息;结合ＰＮＣ及隔ＭＥＰ两者的结果可能有助于判断睡眠呼吸暂停综合征的病变类型。     

Effect of cholinergic drugs on the brainstem auditory evoked responses (far-field) in rats

The present studies were undertaken to provide evidence for the presence of cholinergic mechanisms in the modulation of brainstem (far-field) acoustically evoked potentials in rats. A muscarinic agonist, oxotremorine, produces an increase in the amplitudes of such potentials, while administration of nicotine causes amplitude decrement. Physostigmine and carbachol produced a dose-dependent decrement and increment (biphasic) of the amplitudes. In animals pretreated with scopolamine; oxotremorine, physostigmine and carbachol failed to produce an increment of amplitude; on the other hand a decrement of amplitude was observed with these drugs. Similarly pretreatment with mecamylamine blocked the characteristic depressant effects of nicotine and caused an increase in the far-field potential amplitudes. This could be due to the unmasking of opposite cholinergic receptors in the presence of specific muscarinic or nicotinic blockers.These findings suggest the presence of opposing cholinergic influences in the generation of far-field potentials. The possible mechanisms for the muscarinic and nicotinic modulations of these potentials are discussed.     

Modification of neuromagnetic responses of the human auditory cortex by masking sounds

Summary We have studied the effects of masking sounds on auditory evoked magnetic fields (AEFs) of healthy humans. The AEFs were elicited by 25-ms tones presented randomly to the left or to the right ear, and the responses were recorded over the right auditory cortex. Without masking, the 100-ms deflection (N100m) was of somewhat higher amplitude and of shorter latency for contrathan ipsilateral stimuli. Continuous speech, music, or intermittent noise, delivered to the left ear, dampened N100m to stimulation of both ears without correlated changes in sensation. Intermittent noise had a weaker effect on N100m than speech or music. Continuous noise fed to the left ear dampened both the sensation of and the responses to the left-ear stimuli, with no significant effect on the responses to the right-ear stimuli. The results suggest that the masking effects of continuous noise, seen at the auditory cortex, derive mainly from the periphery whereas the effects of sounds with intensity and frequency modulations take place at more central auditory pathways.     

Brain Event-Related Potentials as Indicators of Early Selective Processes in Auditory Target Localization

To establish the stages of brain processing in an auditory stimulus localization task, event-related potentials (ERPs) were recorded from 24 normal subjects listening to brief white noise stimuli in a free-field situation from front, back, left and right loudspeakers. The subject's task was to respond to ‘target’ stimuli from one designated speaker. Performance varied as a function of sound location, stimuli in the front/back dimension being more difficult to localize than those in the left/right. ERP results, based on averaged waveforms, difference waveforms and the factors derived from a principal components analysis, revealed a series of task related components. Some were relatively transient, others more sustained in character. One brain component showed task related amplitude changes with an onset as early as 15 msec. These changes were target specific for sounds in the easier left/right dimension only. Later components, such as the P300, also varied in amplitude between targets and non-targets, but showed no significant amplitude or latency differences to target stimuli as a function of location, despite the significant performance differences.     

Effect of exogenous nitric oxide on electrogenesis in myelinated and unmyelinated nerve fibers

Extracellular recording was used to study the effect of sodium nitroprusside, a donor of NO, on parameters of action potential and ionic currents in single sciatic nerve fibers and unmyelinated nerve terminals in the sternal muscle in frogs. Sodium nitroprusside significantly decreased the duration of action potential in Ranvier node and the amplitude of afterdepolarization. In motor nerve terminals bathed in low Ca²⁺ saline, sodium nitroprusside increased phase III amplitude of the nerve terminal response corresponding to outward potas-sium currents. Blockade of voltage-dependent potassium channels with 4-aminopyridine abolished the effects of NO. These data indicate that exogenous NO reduced the duration of action potential and afterdepolarization through enhancement of voltage-dependent potassium currents.     

Recording of action potentials and polarization of a single crayfish motor axon through a sucrose-gap capillary suction electrode

Summary A capillary suction electrode was developed which contains in its tip a sucrose-gap. The nerve fiber is pulled by negative pressure through the closely fitting openings of an outer and an inner capillary. The space between these openings is o.1 mm wide and can be perfused with sucrose solution. Because of the small physical size of the electrode tip the electrode can be used to record from single unmyelinated nerve fibers in small preparations in combination with other electrodes or transducers.Action potentials were recorded from branches of the motor axon of the opener muscle of the crayfish claw. The amplitude of the recorded action potentials was 7–22 mV, and all records were monophasic positive. The action potential showed depolarizing but not hyperpolarizing afterpotentials.Hyperpolarization of the nerve fiber by –0.05 to –0.2 A current injected through the recording electrode led to about 50% increase in the amplitude of the recorded action potentials and to a marked prolongation of the depolarizing afterpotentials. Depolarization of the fiber decreased the amplitude of the action potential.This work was supported by the Deutsche Forschungsgemeinschaft.     

Influence of motor unit properties on the size of the simulated evoked surface EMG potential

The purpose of the study was to quantify the influence of selected motor unit properties on the simulated amplitude and area of evoked muscle potentials detected at the skin surface. The study was restricted to a motor unit population simulating a hand muscle whose potentials were recorded on the skin over the muscle. Peak-to-peak amplitude and area of the evoked potential were calculated from the summed motor unit potentials and compared across conditions that simulated variation in different motor unit properties. The simulations involved varying the number of activated motor units, muscle fiber conduction velocities, axonal conduction velocities, neuronal activation times, the shape of the intracellular action potential, and recording configurations commonly used over hand muscles. The results obtained for the default condition simulated in this study indicated that ~7% of the motor unit potentials were responsible for 50% of the size of the evoked potential. Variation in the amplitude and area of the evoked muscle potential was directly related to the number of active motor units only when the stimulus activated motor units randomly, and not when activation was based on a parameter such as motor unit size. Independent adjustments in motor unit properties had variable effects on the size of the evoked muscle potential, including when the stimulus activated only a subpopulation of motor units. These results provide reference information that can be used to assist in the interpretation of experimentally observed changes in the size of evoked muscle potentials.     

Effects of nifedipine on nerve-evoked action potentials and consequent contractions in rat tail artery

The effects of nifedipine on the electrical and mechanical activity recorded from the rat tail artery were examined. Intracellular recordings were obtained from the smooth muscle and vessel diameter monitored during nerve stimulation. Nifedipine (0.1-10 microM) depressed contractions elicited by single and repetitive (2 Hz) stimulation by 32-100% but was ineffective in decreasing the amplitude of the associated action potentials. Concentrations greater than or equal to 10 microM caused a slowly developing membrane depolarization. No change in the amplitude of subthreshold excitatory junction potentials was observed at concentrations of nifedipine less than 50 microM when the membrane depolarization was less than 8 mV. At all concentrations examined nifedipine lowered the stimulus intensity required to initiate an action potential. The amplitude of the nerve-evoked action potential recorded in lowered external Ca2+ (1 mM) was slightly increased (5-10%) by nifedipine. However, nifedipine readily reversed the increased amplitudes of the nerve-evoked action potentials and contractions caused by the addition of 20 mM tetraethylammonium chloride in the tail artery. The action potential recorded in normal solution from the guinea pig vas deferens was selectively abolished by nifedipine.     

Brief Latency Click-Evoked Potentials During Waking and Sleep in Man

Very early auditory evoked potentials, commencing from 1 to 2 msec after stimulation, can be recorded from human scalp by averaging; they appear to be generated in the VIII nerve and brain stem structures. This study was conducted to obtain data concerning possible variations of these early auditory responses with sleep in man. Our results show little or no change in the amplitude and latency characteristics of these potentials from waking to sleep or between sleep stages. Prolonged stimulation, during waking or sleep, produced increases of latency and a tendency for decrease of amplitude. The findings were interpreted to indicate that changes in latency and amplitude of later components of auditory evoked responses during sleep occur at levels above the brain stem. They also support the view that the increased threshold for auditory arousal associated with sleep is mediated centrally rather than peripherally.     

Early development of intrinsic and synaptic properties of chicken nucleus laminaris neurons

Onset of auditory brainstem responses in chickens takes place at about embryonic day 11/12 (E11/12). We investigated early development of neuronal properties of chicken nucleus laminaris neurons, the third-order auditory neurons critically involved in sound localization. Whole-cell patch recordings were performed in brainstem slices obtained at E10, E11, E12, E14, E16, and E18. At E18 neurons acquired an adult-like firing pattern in response to prolonged depolarizing current injections, with a single spike at the onset of the current injection followed by a plateau of membrane potential. At earlier ages, however, multiple spikes and/or subthreshold membrane potential oscillations were generated. We observed a >threefold reduction in input resistance from E10 to E18, and progressive changes in excitability properties, such as elevated threshold currents for spike generation, increased spike rising and falling rates, accompanied by reduced spike width and enhanced ability to follow high frequency inputs. Consistent with development of firing properties, the amplitude of voltage-gated potassium channel (Kv) currents increased by approximately threefold from E10 to E18, with a dramatic increase ( approximately ninefold) in the low threshold component. Excitatory postsynaptic potentials (EPSPs) were first recorded at E10, prior to and independent of the cochlear afferent inputs from the auditory nerve to the cochlear nucleus. EPSPs became markedly briefer in duration during the period studied. We conclude that the basic features of the key neuronal properties of NL neurons are well constructed during early development from E10 to E18.     

Effect of deviance direction and calculation method on duration and frequency mismatch negativity (MMN)

The mismatch negativity (MMN) component of the auditory event-related potential (ERP) reflects the process of change detection in the auditory system. The present study investigated the effect of deviance direction (increment vs. decrement) and calculation method (traditional vs. same-stimulus) on the amplitude of MMN. MMN was recorded for increments and decrements in frequency and duration in 20 adults. The stimuli (standard/deviant) were 250 Hz/350 Hz (frequency MMN) and 200 ms/300 ms (duration MMN) for increment MMN and vice versa for decrement MMN. Amplitude of MMN was calculated in two ways: the traditional method (subtracting ERP to the standard from the deviant presented in the same block) and the same-stimulus method (subtracting ERP to identical stimuli presented as standard in one block and deviant in another block). We found that increments in frequency produced higher MMN amplitudes compared to decrements for both methods of calculation. For duration deviance, the decrement MMN was absent in the traditional method, while the decrement and increment MMN did not differ for the same-stimulus method. These findings suggest that the brain processes frequency increments and decrements in different ways. The results also suggest the use of same-stimulus method for the calculation of duration MMN when long duration stimuli are used.     

Changes in crossed spinal reflexes after peripheral nerve injury and repair

We investigated the changes induced in crossed extensor reflex responses after peripheral nerve injury and repair in the rat. Adults rats were submitted to non repaired sciatic nerve crush (CRH, n = 9), section repaired by either aligned epineurial suture (CS, n = 11) or silicone tube (SIL4, n = 13), and 8 mm resection repaired by tubulization (SIL8, n = 12). To assess reinnervation, the sciatic nerve was stimulated proximal to the injury site, and the evoked compound muscle action potential (M and H waves) from tibialis anterior and plantar muscles and nerve action potential (CNAP) from the tibial nerve and the 4th digital nerve were recorded at monthly intervals for 3 mo postoperation. Nociceptive reinnervation to the hindpaw was also assessed by plantar algesimetry. Crossed extensor reflexes were evoked by stimulation of the tibial nerve at the ankle and recorded from the contralateral tibialis anterior muscle. Reinnervation of the hindpaw increased progressively with time during the 3 mo after lesion. The degree of muscle and sensory target reinnervation was dependent on the severity of the injury and the nerve gap created. The crossed extensor reflex consisted of three bursts of activity (C1, C2, and C3) of gradually longer latency, lower amplitude, and higher threshold in control rats. During follow-up after sciatic nerve injury, all animals in the operated groups showed recovery of components C1 and C2 and of the reflex H wave, whereas component C3 was detected in a significantly lower proportion of animals in groups with tube repair. The maximal amplitude of components C1 and C2 recovered to values higher than preoperative values, reaching final levels between 150 and 245% at the end of the follow-up in groups CRH, CS, and SIL4. When reflex amplitude was normalized by the CNAP amplitude of the regenerated tibial nerve, components C1 (300-400%) and C2 (150-350%) showed highly increased responses, while C3 was similar to baseline levels. In conclusion, reflexes mediated by myelinated sensory afferents showed, after nerve injuries, a higher degree of facilitation than those mediated by unmyelinated fibers. These changes tended to decline toward baseline values with progressive reinnervation but still remained significant 3 mo after injury.     

Calculation of the conduction velocity of short nerve fibres

The conduction velocity v of a nerve fibre is calculated from the time delay Δ of a propagating action potential between two recording sites along the fibre. However, the conventional method of determining Δ cannot be applied to short nerve fibres. Therefore several linear signal analysis methods for the estimation of Δ have been compared with regard to the reproducibility of their results obtained from pairs of simultaneously recorded action potentials at several small inter-electrode distances. It was found that, estimating Δ from the cross-correlogram and as a second one a variant of this method (maximum likelihood time delay estimation) give the most reliable values of v in short nerve fibres.