Antidromic discharge property of meso-accumbens dopaminergic VTA neurons in rats

Three groups of meso-accumbens (Acc) neurons in the ventral tegmental area were differentiated by their antidromic discharge property; dopaminergic type 1 (n = 10), non-dopaminergic type 2 (n = 2) and unclassified (n = 2) neurons. During repetitive activation at 10 Hz, the latency of the initial segment (IS) spike, which was often not followed by the somadendritic (SD) spike, was gradually prolonged in type 1, but not in type 2 and unclassified neurons. The latency prolongation of type 1 neurons was reduced to about a half of the normal in rats treated with kainic acid plus haloperidol, but only slightly when treated with kainic acid or picrotoxin. The rate of SD invasion tended to increase after all kinds of chemical treatment. Stimulation of the medial forebrain bundle in type 1 neurons gave responses comparable to Acc stimulation. It is suggested that the latency prolongation of IS spike is produced mainly by axonal mechanism. But additional somatic mechanisms such as dopaminergic self-inhibition and GABAergic and non-GABAergic inputs from the Acc would make some contribution, and at the same time produce frequent suppression of the antidromic SD spike.     

Reticulospinal vasomotor neurons of the rat rostral ventrolateral medulla: relationship to sympathetic nerve activity and the C1 adrenergic cell group

Neurons projecting from the rostral ventrolateral medulla (RVL) to the spinal cord were antidromically identified in rats anesthetized with urethane, paralyzed, and ventilated. The sites of lowest antidromic threshold were concentrated in the intermediolateral nucleus (IML). Their axonal conduction velocities were distributed bimodally, with the mean of the rapidly conducting fibers (greater than 1 m/sec) being 3.1 +/- 0.1 m/sec (n = 105), and of the slower axons being 0.8 +/- 0.03 m/sec (n = 25). Single-shock electrical stimulation of RVL elicited 2 bursts of excitation in splanchnic sympathetic nerve activity (SNA), which resulted from activation of 2 descending pathways with conduction velocities comparable to those of antidromically excited RVL-spinal neurons. The probability of discharge of RVL-spinal cells was synchronized both with the cardiac-related bursts in SNA with functional baroreceptor reflexes and with the free-running 2-6 Hz bursts in SNA following baroreceptor afferent denervation. On the average, their spontaneous discharges occurred 67 +/- 2 msec (n = 31) prior to the peak of the spontaneous bursts in splanchnic SNA. This time corresponded to the latency to the peak of the early excitatory potential in splanchnic SNA following electrical stimulation of RVL. Baroreceptor reflex activation inhibited RVL-spinal neurons. The recording sites of RVL-spinal vasomotor neurons were consistently located within 100 micron of cell bodies (C1 neurons) immunoreactive for the adrenaline-synthesizing enzyme phenylethanolamine N-methyltransferase (PNMT). Ultrastructural analysis of the lateral funiculus of the cervical and thoracic spinal cord demonstrated PNMT immunoreactivity within myelinated (0.6-2.1 micron diameter) and unmyelinated (0.1-0.8 micron diameter) axons. Estimated conduction velocities of these fibers were comparable to the antidromic conduction velocities of the rapidly and slowly conducting populations of RVL-spinal vasomotor neurons. We conclude that in rat, the discharge of RVL-spinal vasomotor neurons strongly influences SNA: the baroreceptor-mediated inhibition of these neurons is reflected in the cardiac locking of SNA, while, in the absence of baroreceptor input, the synchronous discharge of RVL-spinal neurons maintains a free-running 2-6 Hz bursting pattern in SNA. RVL-spinal neurons are located within, and may be elements of, the C1 adrenergic cell group, and they provide a sympathoexcitatory drive to neurons in the IML over rapidly and slowly conducting pathways that correspond to myelinated and unmyelinated spinal axons containing PNMT.     

Increase in antidromic excitability in presumed serotonergic dorsal raphe neurons during paradoxical sleep in the cat

Putative serotonergic dorsal raphe (DRN) neurons display a dramatic state-related change in behaviour, discharging regularly at a high rate during waking and at progressively slower rates during slow-wave sleep (SWS) and ceasing firing during paradoxical sleep (PS). Using the antidromic latency technique and extracellular recording, we have examined the change in neuronal excitability of presumed serotonergic DRN neurons during the wake-sleep cycle in freely moving cats. We found that, under normal conditions, suprathreshold stimulation of the main ascending serotonergic pathway resulted in a marked decrease in both the magnitude and variability of antidromic latency during PS, while subthreshold stimulation led to a marked increase in antidromic responsiveness during PS compared with during other behavioural states. The antidromic latency shift resulted from a change in the delay between the initial segment (IS) and soma-dendritic (SD) spikes, the antidromic latency being inversely related to the interval between the stimulus and the preceding spontaneous action potential. A marked decrease in the magnitude and variability of antidromic latency was also seen following suppression of the spontaneous discharge of DRN neurons by application of 5-HT autoreceptor agonists or muscimol, a potent GABA agonist. A marked IS-SD delay or blockage of SD spikes was, however, seen in association with the PS occurring during recovery from 5-HT autoreceptor agonist or during muscimol application. The present findings are discussed in the light of previous in vitro intracellular recording data and our recent findings of the disfacilitation mechanisms responsible for the cessation of discharge of DRN neurons during PS.     

Intracellular study of rat globus pallidus neurons: membrane properties and responses to neostriatal, subthalamic and nigral stimulation.

Physiological properties of globus pallidus (GP) neurons were studied intracellularly in anesthetized rats. More than 70% of the neurons exhibited continuous repetitive firing of 2-40 Hz, while others exhibited periodic burst firing or no firing. The repetitively firing neurons exhibited the following properties: spike accommodation; spike frequency adaptation; continuous firing with a frequency of about 100 Hz generated by intracellular current injections; fast anomalous rectification; ramp-shaped depolarization upon injection of depolarizing current; and post-active hyperpolarization. The burst firing neurons evoked a large depolarization with multiple spikes in response to depolarizing current, and a similar response was observed after the termination of hyperpolarizing current. The few neurons which did not fire spontaneous spikes exhibited strong spike accommodation when they were stimulated by current injections. The continuously firing neurons were antidromically activated by stimulation of the neostriatum (Str) (23 of 68), the subthalamic nucleus (STh) (55 of 75), and the substantia nigra (SN) (25 of 46). The antidromic latencies of the 3 stimulus sites were very similar (about 1 ms). None of the burst firing neurons were antidromically activated. Three non-firing neurons evoked antidromic responses only after Str stimulation. Only repetitively firing neurons evoked postsynaptic responses following stimulation of the Str and the STh. Stimulation of the Str evoked initial small EPSPs with latencies of 2-4 ms and strong, short duration IPSPs with latencies of 2-12 ms. Stimulation of the STh evoked short latency EPSPs overlapped with IPSPs. Frequently, these responses induced by Str and STh stimulation were followed by other EPSPs lasting 50-100 ms. These results indicated: (1) that the GP contains at least 3 electrophysiologically different types of neurons; (2) that GP projections to the Str, the STh, and the SN are of short latency pathways; (3) that Str stimulation evokes short latency EPSPs followed by IPSPs and late EPSPs in GP neurons; and (4) that STh stimulation evokes short latency EPSPs overlapped with short latency IPSPs and late EPSPs in GP neurons.     

Septo-hippocampal neurons in the rat: Further study of their physiological and pharmacological properties

Medial septal-nucleus of the diagonal band of Broca area (MS-nDBB) neurons, identified by their antidromic response to the electrical stimulation of the fimbria and/or hippocampus, were studied in the rat under various conditions of anesthesia. These septo-hippocampal neurons (SHNs) were classified into 4 groups on the basis of: (i) their antidromic latency; and (ii) the presence or absence of a rhythmically bursting pattern of spontaneous discharge. The rhythmically bursting activity (43.5% of the SHNs) was highly dependent on the anesthetic conditions. The groups of SHNs differed in their mean conduction velocity and rate of spontaneous activity. In contrast, irrespective of their classification in a particular group, the large majority of the SHNs could be excited by the iontophoretic application of cholinergic agonists. Beside the SHNs, two other populations of MS-nDBB neurons could be identified by electrical antidromic stimulation: neurons projecting to the amygdala (Am) and neurons projecting through the medial forebrain bundle (MFB). Half of the MS-nDBB neurons projecting to Am were also antidromically driven from the fimbria. The axonal branch projecting to Am had a slower conduction velocity than that projecting to hippocampus. In contrast MS-nDBB neurons projecting through the MFB were never antidromically driven from the fimbria, although they received orthodromic inputs. They had a slower conduction velocity than the other groups of MS-nDBB neurons.     

Antidromic activation of dorsal raphe neurons from neostriatum: Physiological characterization and effects of terminal autoreceptor activation

Three types of neurons, distinguished on the basis of their spontaneous firing rates and patterns, extracellularly recorded waveforms and responses to neostriatal stimulation, were observed in the dorsal raphe nucleus in urethane-anesthetized rats. Type 1 neurons (presumed to be serotonergic) fired spontaneously from 0.1 to 3 spikes/s in a regular pattern, with initial positive-going bi- or triphasic action potentials. Type 1 cells exhibited long-latency antidromic responses to neostriatal stimulation (mean +/- S.E.M. 24.9 +/- 0.3 ms) that sometimes occurred at discrete multiple latencies, and supernormal periods persisting up to 100 ms following spontaneous spikes. Type 2 cells fired spontaneously in an irregular, somewhat bursty pattern from 0 to 2 spikes/s with initial negative-going biphasic spikes, and were antidromically activated from neostriatal stimulation at shorter latencies than Type 1 cells (21.8 +/- 0.9 ms). Type 3 cells were characterized by initial positive-going biphasic waveforms and displayed a higher discharge rate (5-30 spikes/s) than Type 1 or Type 2 cells. Type 3 cells could not be antidromically activated from neostriatal stimulation. The relatively long conduction time to neostriatum of the Type 1 presumed serotonergic neuron is discussed with respect to previous interpretations of the synaptic action of serotonin in the neostriatum. In conjunction with these antidromic activation studies, the neurophysiological consequences of serotonergic terminal autoreceptor activation were examined by measuring changes in the excitability of serotonergic terminal fields in the neostriatum following administration of the serotonin autoreceptor agonist, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). The excitability of serotonergic terminal fields was decreased by intravenous injection of 40 micrograms/kg 5-MeODMT, and by infusion of 10-50 microM 5-MeODMT directly into the neostriatum. These results are interpreted from the perspective of mechanisms underlying autoreceptor-mediated regulation of serotonin release.     

Nucleus basalis neurons exhibit axonal branching with decreased impulse conduction velocity in rat cerebrocortex

Single neurons in the basal forebrain (nucleus basalis area) were antidromically activated from the frontal or parietal cortex in anesthetized rats. Wide ranges of antidromic latencies were observed overall, with frontal and parietal stimulation yielding values ranging from 1.0 to 26.0 ms and 1.6-24.0 ms, respectively. Individual neurons often exhibited multiple antidromic latencies, such that deeper sites of stimulation or greater stimulation amplitudes generally yielded discretely different, shorter latencies than more superficial sites or lower amplitudes of stimulation. Single neurons were also often driven from neighboring sites (1-2 mm apart) within the frontal cortex, but no cell was coactivated from both frontal and parietal cortices. Finally, patterns and rates of spontaneous activity varied markedly among these cortically projecting neurons, with some cells being non-spontaneous and others exhibiting tonic rates of 30-40 Hz. Impulse waveforms also differed among driven cells, from relatively low-amplitude, negative spikes to large-amplitude, entirely positive spikes in unfiltered signals. These results indicate that cortically projecting, putatively cholinergic neurons in the basal fore-brain form a physiologically heterogeneous population in terms of impulse conduction velocity, spontaneous discharge, and spike waveforms. Our finding of multiple antidromic latencies and driving from neighboring sites indicate that these fibers may be highly branched in local terminal fields, but that individual cells may project exclusively to a single cortical area. Faster conduction velocities for deep compared to superficial cortical stimulation sites imply that these fibers may become non-myelinated upon entering cortical terminal fields, or that they may become markedly thinner as they travel within the cortex. This system of cholinergic cortical afferents differs in many physiologic aspects from the other non-thalamic cortical input systems of catecholamine or indoleamine neurons.     

Pallidal inputs to subthalamus: Intracellular analysis

Neuronal responses of the subthalamic nucleus (STH) to stimulation of the globus pallidus (GP) and the substantia nigra (SN) were studied by intracellular recording in the decorticated rat. (1) GP and SN stimulation evoked antidromic spikes in STH neurons with a mean latency of 1.2 ms and 1.1 ms, respectively. Based on the above latencies, the mean conduction velocity of the STH neurons projecting toward GP was estimated to be 2.5 m/s, and that toward SN was 1.4 m/s. Many STH neurons could be activated following stimulation of both GP and SN, indicating that single STH neurons project to two diversely distant areas. In spite of differences in conduction distance of GP and SN from STH, differences in the conduction velocities of bifurcating axons make it possible for a simultaneous arrival of impulses in the target areas to which these STH neurons project. (2) GP stimulation evoked short duration (5-24 ms) hyperpolarizing potentials which were usually followed by depolarizing potentials with durations of 10-20 ms. These potentials were tested by intracellular current applications and intracellular injections of chloride ions. The results indicated that the hyper- and depolarizing potentials were IPSPs and EPSPs respectively. These IPSPs were considered to be monosynaptic in nature since changes in the stimulus intensities of GP did not alter the latency of IPSPs. The mean latency of the IPSPs was 1.3 ms. Based on the above mean latency the mean conduction velocity of GP axons projecting to STH was estimated to be 3.8 m/s. (3) Analysis of electrical properties of STH neurons indicated that: (i) input resistance estimated by a current-voltage relationship ranged from 9 to 28 M omega; (ii) the membrane showed rectification in the hyperpolarizing direction; (iii) direct stimulation of neurons by depolarizing current pulses produced repetitive firings with frequencies up to 500 Hz. (4) Morphology of the recorded STH neurons was identified by intracellular labeling of neurons with horseradish peroxidase. Light microscopic analysis indicated that the recorded neurons were Golgi type I neurons with bifurcating axons projecting toward GP and SN.     

Evidence of facilitatory coerulospinal action in lumbar motoneurons of cats

Functional connectivity of the feline coerulospinal projection was delineated by utilizing the combined approaches of antidromic activation and electrical stimulation. We isolated 25 locus coeruleus (LC) neurons that were electrophysiologically identified and histologically verified and that could be driven by stimulating the spinal cord. Antidromicity of the spike potentials was confirmed by the constant latency, the high frequency (100 Hz) following, fractionation of the initial segment-somatodendritic potential, and collision between the antidromic and the spontaneous orthodromic spikes. The mean conduction speed was20 ± 8m/sec(range= 7to32m/sec). Intracellular studies revealed facilitatory LC actions in 22 lumbar motoneurons (MNs), In 13 MNs, LC activation alone produced slow-rising excitatory postsynaptic potentials (EPSPs) of3 ± 1mV amplitude that lasted 4–30 msec. Six of the 13 MNs discharged action potentials upon LC stimulation. In the remaining 9 MNs, no observable potential change was registered after LC activation. Antecedent LC stimulation consistently potentiated the synaptic efficacy of testing dorsal root shocks. The enhancement of synaptic activation was antagonized by systemic injection of phenoxybenzamine (3 mg/kg). These results suggest that facilitation of MNs by the LC is at least in part mediated by distal dendritic depolarization. Those MNs that exhibited augmented excitability but no demonstrable EPSPs may have been activated by norepinephrine-mediated synaptic modulation.     

Response of rat superior salivatory units to chorda tympani stimulation

Unit responses to chorda tympani stimulation in urethane anesthetized rats were characterized by response latency and frequency following ability. One hundred and fifty one units responded with constant latencies, mean: 16.9 msec, S.D.: 7.8 msec. Responses recorded from within the superior salivatory nucleus (SSN) had significantly longer latencies (18.8 ± 6.8, n = 94) than those from surrounding areas (13.5 ± 8.3, n = 50) (p < 0.001). This difference was due to the higher incidence of responses with latencies between 2.7 and 10 msec outside of the SSN (44%) compared to SSN responses (8%). Ability to follow high frequency stimulation ranged from 2–550 Hz, and was the same for SSN neurons and those outside the nucleus. The population of responses localized to the SSN, with latencies greater than 10 msec and with high (> 100 Hz) frequency following, had a mean latency of 20.5 msec. The estimated conduction velocity for these presumed preganglionic, parasympathetic neurons is 0.85 M/sec ± 0.25, significantly slower than that reported for similar responses in cats. The antidromic nature of these responses requires confirmation.     

The reciprocal electrophysiological influence between the nucleus tegmenti pedunculopontinus and the substantia nigra in normal and decorticated rats

The electrophysiological characteristics of neurons of the nucleus tegmenti pedunculopontinus (PPN), in particular of those projecting to the substantia nigra (SN), and the reciprocal influence between the PPN and SN were investigated in normal and decorticated rats. In intact animals 65 of the 363 PPN recorded neurons (17.9%) were activated antidromically by SN stimulation, 96 (26.3%) were inhibited after stimulation while 43 (11.8%) were activated. In decorticated rats excitatory responses were decreased (4.8%) while antidromic and inhibitory responses did not change substantially. Electrical stimulation of the PPN induced a brief short-latency excitation of SN neurons (26/77, 33.7%) which was not modified by removing the cortex bilaterally 7-10 days prior to the recording session. This excluded the possibility that corticofugal fibers could be involved in the excitatory responses evoked by PPN stimulation in SN neurons. The latency of the antidromic response evoked in PPN cells by SN stimulation ranged from 0.5 to 12.0 ms and the estimated conduction velocity of these PPN output neurons ranged from 1.1 to less than 0.5 m/s. The electrophysiological heterogeneity of PPN cells was supported also by the fact that two types of neurons, both projecting to the SN, could be distinguished on the basis of their spontaneous firing rate and impulse waveform. The first had a low spontaneous activity (0.5-8 spikes/s) with a triphasic impulse which lasted 3-4 ms. The second had a high firing rate (15-20 spikes/s) and its impulse was usually biphasic and not longer than 3 ms.(ABSTRACT TRUNCATED AT 250 WORDS)     

Physiological properties of ascending locus coeruleus axons in the squirrel monkey

Discharge activity was recorded extracellularly from individual neurons of the nucleus locus coeruleus in anesthetized squirrel monkeys. These cells exhibited long-duration (2-3 ms) action potentials and discharged spontaneously in a slow (0.2-2 Hz) irregular fashion. Stimulation of the lateral hypothalamus evoked antidromic responses at latencies of 10-20 ms, indicating conduction velocities of over 1 m/s in some cases. The mean refractory period for these axons was 2.6 ms. When the rate of hypothalamic stimulation was increased from 1 to 10 Hz there was a 15-20% increase in antidromic latencies. These properties are similar to those previously observed for rat LC neurons, except that conduction velocities are higher in monkey.     

Dopaminergic neurons in the rat ventral tegmental area. III. Effects of -and -amphetamine

By use of various histochemical techniques, it was shown that both DA and non-DA cells in the VTA project to the NAc. Of these VTA-NAc output cells, the great majority were DA-containing cells. A small number of non-DA cells were encountered most frequently in the lateral part of the VTA. Correspondingly, two distinct groups of neurons, types I and II, could be identified by antidromic stimulation of the NAc. Several lines of evidence suggest that type I cells are DA-containing neurons. The evidence may be summarized as follows:

1. (1) type I cells had a slow-bursting or regular firing pattern, slow discharge rate and wide spike duration which appears to be identical to the characteristics of DA neurons originally described by Bunney et al.¹⁶;

2. (2) the great majority of these cells could be activated antidromically by stimulation of the NAc;

3. (3) the conduction velocity and absolute refractory period of type I cells are consistent with unmyelinated fine DA fibers;

4. (4) injection of 6-OHDA, but not 5,7-DHT directly in the MFB blocked antidromic responses of these cells;

5. (5) they were extremely sensitive to intravenously administered DA agonist apomorphine (ID₅₀ = 7 μg/kg); and

6. (6) direct fluorescence histochemical examination of serial sections from brains of animals in which type I cells have been identified by antidromic stimulation of the NAc showed that type I cells are most likely catecholamine-containi ng neurons. By contrast, type II cells possessed an entirely different spectrum of physiological characteristics; in addition, they showed no consistent response to apomorphine and their antidromic responses to stimulation of the NAc were not affected by 6-OHDA. It is concluded that (1) VTA output neurons consist of both DA and nonDA neurons, and (2) identified types I and II neurons in the VTA by antidromic stimulation of the NAc are DA and non-DA cells, respectively.

Extra- and intracellular recordings from dorsal column postsynaptic spinomedullary neurons in the cat

Dorsal column postsynaptic (DCPS) spinomedullary neurons in the dorsal horn of spinal segments L6-S1 of adult cats anesthetized with sodium pentobarbital were identified by antidromic stimulation of cervical dorsal columns that were dissected free of, and electrically isolated from, the rest of the spinal cord. The neurons were categorized with respect to natural stimulation of their cutaneous receptive fields. An equal number of low-threshold mechanoreceptive and wide-dynamic-range neurons were found. No DCPS neurons could be classified as nociceptive-specific. All neurons received input from low-threshold mechanoreceptors with myelinated axons. There was no evidence that any neurons received monosynaptic input from unmyelinated, primary afferent fibers. The average conduction velocity of the antidromic responses was 45.7 m/s. Nearly half of the DCPS cells showed an antidromic spike followed by synaptically driven responses that were probably evoked by antidromic invasion into the intraspinal collaterals of A-beta primary afferent fibers that ascended the dorsal columns. Intracellularly recorded synaptic responses of DCPS neurons to dorsal column and receptive field stimulation usually consisted of an EPSP with overriding spike potentials followed by a prolonged IPSP whose amplitude decreased markedly as the stimulus frequency was increased in the range of 5 to 30 Hz. The results indicate that DCPS neurons constitute a projection system capable of signaling innocuous and tissue-damaging mechanical stimuli. The DCPS projection may play a role in the modulation of touch and pain perception.     

Effects of a distant noxious stimulation on A and C fibre-evoked flexion reflexes and neuronal activity in the dorsal horn of the rat

In the halothane-anaesthetized rat, the responses of 49 neurons in the lumbo-sacral cord and the reflex discharge in the common peroneal nerve following electrical stimulation of the sural nerve were recorded in order to study possible relations between neuronal events and reflex nerve discharges. A distant noxious stimulus (to activate Diffuse Noxious Inhibitory Controls (DNIC) of Le Bars et al.) was used as a conditioning stimulus. Only the responses of neurons receiving an input from both A and C fibres were studied. The neurons were classified as class 1 (low threshold mechanoreceptive input only, n = 2), class 2 (nonnoxious and noxious inputs, n = 34) or class 3 (responding to noxious stimuli only, n = 13). During conditioning stimulation the C fibre evoked discharge was inhibited in 32 out of 34 class 2 neurons. The A fibre-evoked discharge was simultaneously inhibited in 29 of these neurons. The main effect of the distant noxious stimulation on the C fibre evoked neuronal discharge was to decrease the discharge by a constant number of spikes, independent of the level of evoked activity. Only one class 3 neuron was inhibited during conditioning stimulation and none of the class 1 cells were influenced by DNIC. During conditioning stimulation the late and prolonged C fibre evoked reflex nerve discharge (latency 160-200 ms, duration up to several hundred ms) was strongly depressed. Concomitantly, a short-lasting reflex nerve discharge appeared over the interval 115-160 ms. This released reflex nerve discharge (RR) had a constant latency. There was no simultaneous change of the A beta evoked reflex nerve discharge. After the end of the distant noxious stimulation the late C fibre evoked reflex nerve discharge (latency 160-200 ms) recovered. Concomitantly, the RR disappeared. The possibility that the class 2 neurons and the class 3 neurons are intercalated in different reflex pathways is discussed.     

An automatic device for determining threshold variations in antidromically activated neurons

A device was designed and constructed with the purpose of evaluating threshold variations for antidromic invasion of extracellularly recorded neurons. Identification of a neuron is carried out by two procedures, an amplitude discriminator, which isolates the spike from the baseline noise, and by a latency window which is set accordingly to the neuron's antidromic latency. During threshold evaluation, the duration of an electric pulse applied to the neuron's axon is automatically varied depending on the presence or not of an action potential. For a given spike, the stimulus is progressively decreased (-delta i) up to a point where the neuron ceases to respond and thereafter, the stimulus amplitude is progressively increased (+delta i) until slightly suprathreshold values are obtained. The procedure guarantees a discharge probability of the neuron equivalent to 50% of all applied stimuli, and the simple monitoring of the stimulus amplitude is enough to obtain the threshold value for a predetermined intensity. The reliability of this device was checked in studies related to threshold variations in neurons antidromically driven in prefrontal cortex following stimulation of the ipsi and contralateral olfactory bulb. Variations in excitability were found during and following tetanic stimulation and throughout the axon's supernormal conduction period. This technique allows the assessment of threshold variations in antidromic driving, not only in the present experimental design, but also in other conditions induced by changes in extracellular ionic concentrations, drug applications or in those produced by excitatory or inhibitory synaptic activity on the neuron under study.     

Variations in conduction velocity and excitability following single and multiple impulses of visual callosal axons in the rabbit

The present study examined the conduction properties of 75 visual callosal axons of the awake rabbit. These axons were studied by measuring latency to antidromic activation of cell bodies following midline callosal and/or contralateral cortical stimulation. Seventy-three of 75 neurons (axon conduction velocities = 0.3 to 12.9 m/sec) demonstrated decreases in antidromic latency and threshold to a test stimulus which followed an antecedent conditioning stimulus at appropriate intervals. Control experiments indicated that (i) the latency and threshold variations resulted from prior impulse conduction along the axon, and (ii) the latency decrease reflected an increase in conduction velocity along the main axon trunk. The maximum magnitude of the latency decrease for different axons ranged from 3 to 22% of control values, and the duration ranged from 18 to 169 msec. The duration of the latency decrease was greater for slowly conducting axons than for fast conducting axons. Latency increases to an antidromic test stimulus occurred for up to several minutes following a train of antidromic conditioning pulses. Antidromic latency and threshold shifts were also observed in somatosensory callosal axons and in some corticotectal axons.     

Systematic variations in the conduction velocity of slowly conducting axons in the rabbit corpus callosum

Extracellular spikes were recorded from the cell bodies of antidromically activated callosal axons in rabbit visual cortex. Callosal axons were stimulated near their terminals in the contralateral cortex. The primary method for differentiating antidromic from synaptic activation was the test for collision of impulses. Additional tests provided further confirmation of antidromic activation. A decrease in antidromic latency always occurred when an antidromic volley followed either a spontaneous spike or a preceding antidromically elicited spike at appropriate intervals. The time course and magnitude of the latency decrease coincided with that of a threshold decrease at the site of electrical stimulation. The antidromic latency decrease was primarily due to an increase in axon conduction velocity. These systematic variations in conduction velocity and stimulus threshold strongly suggest that an afterdepolarization follows the activation of callosal axons. While such afterpotentials are known to occur in unmyelinated C fibers, the present evidence suggests that they also occur in the smallest of myelinated axons.     

The effects of a distant noxious stimulation on A and C fibre-evoked flexion reflexes and neuronal activity in the dorsal horn of the rat

In the halothane-anaesthetized rat, the responses of 49 neurons in the lumbo-sacral cord and the reflex discharge in the common peroneal nerve following electrical stimulation of the sural nerve were recorded in order to study possible relations between neuronal events and reflex nerve discharges. A distant noxious stimulus (to activate Diffuse Noxious Inhibitory Controls (DNIC) of Le Bars et al.¹⁹) was used as a conditioning stimulus. Only the responses of neurons receiving an input from both A and C fibres were studied. The neurons were classified as class 1 (low threshold mechanoreceptive input only, n = 2), class 2 (nonnoxious and noxious inputs, n =34) or class 3 (responding to noxious stimuli only, n = 13). During conditioning stimulation the C fibre evoked discharge was inhibited in 32 out of 34 class 2 neurons. The A fibre-evoked discharge was simultaneously inhibited in 29 of these neurons. The main effect of the distant noxious stimulation on the C fibre evoked neuronal discharge was to decrease the discharge by a constant number of spikes, independent of the level of evoked activity. Only one class 3 neuron was inhibited during conditioning stimulation and none of the class 1 cells were influenced by DNIC. During conditioning stimulation the late and prolonged C fibre evoked reflex nerve discharge (latency 160–200 ms, duration up to several hundred ms) was strongly depressed. Concomitantly, a short-lasting reflex nerve discharge appeared over the interval 115–160 ms. This released reflex nerve discharge (RR) had a constant latency. There was no simultaneous change of the Aβ evoked reflex nerve discharge. After the end of the distant noxious stimulation the late C fibre evoked reflex nerve discharge (latency 160–200 ms) recovered. Concomitantly, the RR disappeared. The possibility that the class 2 neurons and the class 3 neurons are intercalated in different reflex pathways is discussed.