Orthodromic Activation Research Articles

Organization of cortical afferent and efferent pathways in the white matter of the rat visual system

Fibers forming reciprocal connections between the dorsal lateral geniculate nucleus and primary visual cortex run in separate tracts in the white matter. The corticofugal fibers are organized into bundles which project through the coronal plane at an oblique angle. We have examined the organization of corticofugal fiber tracts within the white matter of the rat using cortical slices which encompassed the predicted trajectory of these fiber bundles. Field potentials were evoked in layer VI of visual cortex by focal stimulation of subcortical white matter using microbipolar electrodes. Two major responses were elicited: a short-latency and a longer-latency response. The short-latency response was elicited in the superficial strata of white matter with proximal stimulation sites and was obtained in deeper strata for more distant, lateral sites. The longer-latency response was associated with superficial strata in white matter at both proximal and distant stimulation sites. Based on the electrophysiological properties and the white matter location for eliciting these responses, it is likely that the short-latency response is due to antidromic activation of corticogeniculate fibers, whereas the longer-latency response probably arises from orthodromic activation of geniculocortical fibers. These findings provide an electrophysiological demonstration that cortical afferent and efferent pathways are segregated within the white matter and that they can be selectively activated by focal stimulation. The fact that the fiber bundle model successfully predicted the trajectory of corticofugal fibers provides additional support for this model of white matter organization. A double labeling technique which combined orthograde axonal transport and neuronal degeneration was used to examine the topographic arrangement of corticofugal fibers in the white matter.(ABSTRACT TRUNCATED AT 250 WORDS)

Rubrospinal tract of the cat: superposition of antidromic responses and changes in axonal excitability following orthodromic activity

Activity was recorded from rubrospinal neurons (RSNs) in anesthetized, paralyzed, artificially ventilated cats. Multiple-unit microelectrodes were used to simultaneously record the activity of neighboring RSNs. When antidromically activated, the RSNs responded forming 'stacks' of superimposed spikes. By using appropriate collision tests, it was found that the spikes forming a stack arose from different neurons. In addition, single extracellular and intracellular recordings were obtained from RSNs. The changes in the axonal excitability of rubrospinal axons were tested following synaptically evoked (by contralateral interpositus (IP) stimulation) and/or directly evoked (by injection of current through the intracellular electrode) action potentials at different postspike delays. Subthreshold stimuli for antidromic activation in absence of orthodromic activity were well suprathreshold for most fibers in a wide range of postspike delays. The supernormal axonal periods were longer-lasting when tested after synaptic spikes (up to an average delay of 100.4 ms; range, 10-500 ms) than after directly evoked spikes (mean delay, 78.8 ms; range, 10-296 ms). If synaptic stimulation fires more RSNs than direct stimulation, then the longer-lasting supernormal periods might be due to the activity of adjacent fibers. An additional increase in external potassium concentration in the vicinity of the axon would explain these results.

Dorsal raphe neuronal responses to thalamic centralis lateralis and medial prefrontal cortex electrical stimulation

The present study gives evidence for ascending pathways from the dorsal raphe nucleus (DR) to the centralis lateralis nucleus (CL) and to the medial prefrontal cortex (PFCx). Single-unit recordings were done at dorsal raphe level and electrical stimulation was applied at CL and PFCx regions causing antidromic and orthodromic activity in DR cells. The speed conduction difference of the antidromic DR responses to CL and PFCx stimulation was significantly different, but the latencies of the same responses showed no differences. Therefore, we conclude that the DR pathways to CL and to PFCx structures reach their target cells at similar times.

Transneuronal regulation of protein synthesis in the brain-stem auditory system of the chick requires synaptic activation

The cellular mechanisms by which afferents influence their target neurons were investigated using a slice preparation of the chick brain-stem auditory system. Each brain slice contained portions of the auditory nerve and the second-order auditory nucleus, nucleus magnocellularis (NM), bilaterally. NM neurons on one side of the slice were stimulated either orthodromically, via activation of the ipsilateral auditory nerve, or antidromically, via electrical stimulation of their axons. NM neurons on the other side of the slice were not stimulated and served as a within-animal control population. Evoked activity was monitored extracellularly in all preparations. Orthodromic activation of NM neurons for either 1.5 or 3.5 hr resulted in enhanced protein synthesis by these neurons. This result is similar to those of previous in vivo experiments (Steward and Rubel, 1985; Born and Rubel, 1988). When slices were maintained in a medium having low Ca2+ and high Mg2+ concentrations, both synaptic transmission from the auditory nerve to NM and also the difference in protein synthesis between the stimulated and unstimulated sides of the brain were blocked. Antidromic activation of NM neurons did not enhance protein synthesis, but rather resulted in reliably less synthesis by the stimulated cells. Together, these results suggest that activity-dependent release of some "trophic" substance from the auditory nerve is necessary for this form of transneuronal regulation. Electrical activity of the postsynaptic neuron per se is not sufficient for increasing protein synthesis in these cells.

Brain stem responses to electrical stimulation of ventral vagal gastric fibers.

The brain stem neuronal responses to electrical stimulation of gastric branches of the ventral vagal trunk serving the proximal stomach were localized and evaluated in anesthetized cats. The responses were equally distributed bilaterally in the region of nucleus solitarius in the caudal brain stem. The mean latency of the response was 289 +/- 46 (SD) ms, which translated into a conduction velocity of less than 1 m/s based on the distance between the stimulating and recording electrodes. The responses consisted of single and multiple spikes that showed slight variability in the latency, indicating orthodromic activation via a synapse in approximately 98% of the responses recorded. Forty two percent of the units tested showed evidence of convergence of input from vagal afferent fibers in different branches of the ventral vagal trunk that served the proximal stomach. The resultant activity pattern of the unitary response appeared to be the product of 1) the gastric sensory input or modality conveyed by the afferent source and 2) the time of arrival and diversity of modalities served by other gastric afferents impinging on the unit. This provides a mechanism capable of responding on the basis of specific sensory modalities that dynamically reflect ongoing events monitored and conveyed by other gastric afferents in the region.

Antidromic firing occurs spontaneously on thalamic relay neurons: Triggering of somatic intrinsic burst discharges by ectopic action potentials

Eighty-two identified thalamocortical relay neurons were recorded extracellularly in the ventral posterior thalamic nucleus in 29 urethane-anaesthetized rats. Electrical stimulations were applied to the contralateral vibrissae or to the ipsilateral neocortex for ortho- or antidromic activation. The critical period following a known somatic action potential and during which no antidromic response could reach the soma was systematically determined for each cell using a collision test. Thus, the possible ectopic axonal origin of a given impulse could be determined. Thalamic neurons displayed either tonic or phasic firing modes, the latter characterized by episodes of rhythmic high-frequency burst discharges. The present results suggest that such bursts were generated at the soma and probably involved an intrinsic mechanism, since: (1) a modulation of the somatic excitability with an excitatory or inhibitory amino acid affected the intra-burst structure; (2) an antidromic test action potential collided with the second or any of the later impulses of such bursts; (3) an orthodromic activation could evoke a burst structurally similar to a natural one; and (4) the duration of the first interval of such an evoked burst was always inferior to the sum of the critical period plus the antidromic conduction time, ruling out the possibility that it might have been entirely ectopically generated on thalamic terminals. The results further show that a spontaneous ectopic axonal impulse could trigger a somatic burst, since: (1) an electrically-evoked antidromic action potential could trigger a burst structurally similar to a spontaneous one; (2) on 42% of the tested thalamic cells, a known antidromic action potential delivered during the critical period following a spontaneous single impulse could not collide with it: in many cases such non-collisions were seen with the first action potential of a burst; and (3) with increasing ionophoretic doses, GABA could: (i) convert bursts to single action potentials, while the ortho- but not the antidromic responses were abolished, (ii) block these single impulses at similar doses than those which abolished known antidromic ones, and (iii) multiply by a factor of 3 the probability of testing an ectopic action potential. On 70% of the cells tested, such GABA-isolated impulses could be proved to have been ectopically generated. Finally, ectopic impulses have never been observed during periods of tonic firing, indicating that such a feature was not an experimental artifact.(ABSTRACT TRUNCATED AT 400 WORDS)

High-frequency discharge of dentate granule cells, but not long-term potentiation, induces c-fos protein

Competence genes, such as c-fos, may play key roles in information storage in the nervous system by linking relatively brief extracellular signals to long-term changes in the neuron. In support of this idea we, and others, have shown that the c-fos protein occurs in adult mammalian neurons and that higher levels of the protein are induced in certain brain regions after kindled or metrazol-induced seizures in mice and rats, sensory stimulation and mechanical damage in spinal cord neurons, and after depolarization in PC12 cells. Here we report that a massive induction of c-fos protein is observed in dentate granule cells in four conditions that result in repetitive firing: localized seizure discharges; high frequency antidromic activation; orthodromic activation in the presence of iontophoresed bicuculline; and frequency potentiation. However, stimulation of the perforant path with high frequency trains that produced long-term potentiation at the perforant path-granule cell synapse did not reliably induce c-fos in the dentate gyrus. These findings suggest that c-fos induction can follow repetitive neuronal discharge but is not involved in long-term potentiation.

An electrophysiological study of the in vitro, perfused brain stem-cerebellum of adult guinea-pig.

1. We describe here a technique which allows the long-term in vitro survival of the perfused isolated brain stem-cerebellum of adult guinea-pig. The viability of this preparation was assessed by comparing the electrophysiological properties of individual neurones and of neuronal pools to those obtained in vivo or in brain slices. The areas investigated included the cerebellar cortex, the inferior olive and the pontine nuclei. 2. Cerebellar field potential and intra- and extracellular single-cell recordings could be obtained for as long as 15 h after the preparation was initially isolated. The waveforms of field potentials recorded at various depths in the cerebellar cortex following surface folial stimulation were similar to those recorded in vivo. Extracellular recordings from single Purkinje cells following white matter stimulation demonstrated antidromic as well as mossy- and climbing fibre-mediated excitation. Stimulation of the cerebellar surface elicited orthodromic parallel fibre excitation of Purkinje cells and basket-stellate and Golgi cell inhibition. 3. Intrasomatic and intradendritic recordings from Purkinje cells reproduced all the phenomenology described earlier under in vivo conditions and in vitro slice preparations. In addition, spontaneous excitatory synaptic potentials generating simple spikes (mossy fibre-parallel fibre-mediated activity) and complex spikes (climbing fibre-mediated activity) were consistently observed. 4. Extracellular field potentials and extra- and intracellular recordings from inferior olive neurones were similar to those previously shown for the mammalian inferior olive. 5. Intracellular recordings were also obtained from pontine nuclei neurones, a major source of mossy fibre afferents to the cerebellum. Stimulation of the contralateral superior cerebellar peduncle produced antidromic invasion of these neurones whereas stimulation of the ipsilateral inferior cerebral peduncle resulted in their orthodromic activation. 6. The preparation responded to pharmacological challenge in a manner which demonstrated a sequential activation of sets of synaptic links in a given pathway. Thus, harmaline generated oscillations of inferior olivary neurones which were similar to those observed in vivo and which produced climbing fibre EPSPs in Purkinje cells at the same frequency as the inferior olivary oscillations. Climbing fibre activation of the Purkinje cells generated powerful inhibitory potentials in the cerebellar nuclear neurones at the same frequency.(ABSTRACT TRUNCATED AT 400 WORDS)

Orthodromic activation of juxta-abducens neurons following sixth nerve stimulation in the cat

Intracellular electrophysiological and morphological (horseradish peroxidase) techniques were used to identify neurons just rostral and ventral to the cat abducens nucleus. These cells responded orthodromically to stimulation of the ipsilateral VIth nerve. Cells seen in previous investigations, which responded similarly, were thought to lie within the principal abducens nucleus. The neurons identified here may be involved in the transmission of some abducens afferent information to higher brain centers.

The primate spinocervicothalamic pathway: responses of cells of the lateral cervical nucleus and spinocervical tract to innocuous and noxious stimuli.

1. The response properties of neurons of the spinocervicothalamic pathway were studied in anesthetized macaque monkeys. Graded innocuous and noxious mechanical stimuli, including sinusoidal vibration and thermal pulses, were applied to the cutaneous receptive fields. 2. Forty-nine cells in the lateral cervical nucleus (LCN) were identified by antidromic activation from the ventral posterior lateral (VPL) nucleus of the contralateral thalamus. Twelve spinocervical tract (SCT) cells in the lumbosacral enlargement of the spinal cord were identified by antidromic activation from stimulation of the ipsilateral dorsolateral funiculus below C3 but not above C1. 3. Latencies for antidromic activation of LCN neurons averaged 2.3 ms, corresponding to a mean conduction velocity of approximately 17 m/s. Mean latency for orthodromic activation of LCN neurons following electrical stimulation of peripheral nerves was 12.6 ms. Overall mean conduction velocity for the monkey spinocervicothalamic pathway was estimated to be 29 m/s. 4. Most LCN cells had receptive fields on hairy skin, but some had input from glabrous skin and a few had subcutaneous fields. The receptive fields of most SCT cells had a glabrous skin component. Receptive fields tended to be smaller for SCT than LCN cells even for fields on a comparable part of the distal hindlimb. 5. Based on their responses to a series of mechanical stimuli (brushing, pressure, pinch, and squeeze), LCN and SCT cells were classified as low-threshold (LT), wide dynamic range (WDR), or high-threshold (HT) neurons. Most of the cells were in the LT or WDR classes. Thus the spinocervicothalamic pathway in the monkey differs from the spinothalamic tract (STT), in that STT cells are generally of the WDR or HT classes. 6. With the use of discriminant analysis, LCN and SCT neurons were allocated to categories determined from a k-means cluster analysis of the responses of 318 STT cells. The LCN and SCT neurons were in different proportions in the various categories than were STT cells, suggesting differences in the signaling properties of the spinocervicothalamic and spinothalamic paths. 7. Innocuous steady indentation of the skin failed to excite any of the neurons tested. Thus no positive evidence was obtained for an input to LCN neurons from slowly adapting mechanoreceptors. 8. Sinusoidal vibratory stimuli were used to test the ability of LCN and SCT neurons to follow repeated innocuous mechanical stimuli. Vibration at 10 Hz and an amplitude of 100 micron resulted in repetitive discharges in most LCN neurons and half the SCT neurons tested; many LCN neurons had thresholds below 25 micron.(ABSTRACT TRUNCATED AT 400 WORDS)

Direct connections between the central nucleus of the amygdala and the nucleus of the solitary tract: an electrophysiological study in the rat.

Reciprocal connections between the central nucleus of the amygdala (CNA) and the nucleus of the solitary tract (NST) have been implied from anatomical studies in the rat and physiological studies in other species. Our work supports this conclusion in that microstimulation of the NST caused both antidromic and orthodromic activation of neurons in the CNA. The distribution of CNA neurons activated by NST stimulation suggests that the dorsomedial portion of the CNA provides input to the dorsal medulla while the ventrolateral CNA receives input from the NST.

Sympathoexcitatory neurons of rostral ventrolateral medulla exhibit pacemaker properties in the presence of a glutamate-receptor antagonist

Intracisternal (i.c.) administration of the glutamate-receptor antagonist kynurenate to halothane-anesthetized rats (paralyzed, ventilated) produced an initial hypertension associated with an increase in lumbar sympathetic nerve discharge. Kynurenate (i.c.) blocked or greatly reduced all sympathetic reflexes investigated (somatosympathetic 70% reduction; vagal pressor and depressor responses, 100%; hypothalamic mixed responses, 90%; baroreflex, 100%) and increased the firing rate of reticulospinal sympathoexcitatory cells of the rostral ventrolateral medulla (PGCL-SE neurons) by 33%. After i.c. kynurenate, these cells exhibited a rhythmic, non-bursting firing pattern which could be reset by spinal cord stimulation only when antidromic spikes were elicited. Cells with similar characteristics were recorded in the nucleus paragigantocellularis lateralis (PGCL) in an in vitro rat bulb preparation perfused through the basilar artery. Their 'pacemaker-like' discharge pattern was observed even in the absence of kynurenate and was reset by orthodromic activation. Cells with similar characteristics were also recorded within the PGCL in 500-microns coronal slices in vitro. At 37 degrees C their discharge rate was similar to that of PGCL-SE neurons recorded in vivo after i.c. kynurenate; it was also pacemaker-like and was insensitive to glutamate receptor blockade. It is suggested that the tonic discharge of PGCL-SE neurons is normally due to an intrinsic pacemaker activity which is modulated in vivo by a variety of synaptic inputs.

Spontaneous activity in afferent and efferent fibers after chronic axotomy: response to potassium channel blockade.

Distally propagating spontaneous impulses in acutely and chronically cut rat saphenous nerve were examined to determine (1) the origin(s) of the activity, (2) the fiber types involved, and (3) whether the activity was affected by potassium channel blockade. Under deep pentobarbital anesthesia, six male Sprague-Dawley rats underwent L3 cauda equina section, then unilateral saphenous axotomy. The nerve was then dissected into 30-50 microfilaments and surveyed for spontaneous activity using a modification of the microfilament recording method. Afterward, the nerve was cut back, and a potassium channel blocking agent (gallamine) was administered. The axonal activity was once again surveyed in the same fashion. Twenty-eight rats underwent unilateral saphenous axotomy 1-8 weeks prior to similar recordings, and the neuroma was excised just before microfilament dissection. Spontaneous discharges in these preparations originated from three foci: (1) antidromic activity from in-continuity dorsal root ganglia (DRG), (2) orthodromic activity from sympathetic neurons, and (3) antidromic activation of dichotomizing afferent axons in the peripheral nerve. There was significantly more antidromic activity from DRG in rats with prior axotomies than in control animals (t = 2.38; p less than 0.025), and gallamine produced a significant increase in DRG activity in the chronically lesioned nerve (t = 2.43; p less than 0.005), but not in acutely lesioned controls. However, most of the spontaneous activity in these preparations was from sympathetic efferents. This activity was decreased significantly by chronic axotomy (t = 2.635; p less than 0.01), and it was not affected by potassium channel blockade with gallamine. In two microfilaments, spontaneous antidromic action potentials were observed in conjunction with a clear receptive field on blood vessels in the nearby fascia. Both of these presumably dichotomized axons were found in acutely cut nerve, thus were not the result of retrograde sprouting from a neuroma. It was concluded that (1) chronic axotomy of sensory afferents produced ectopic activity in their respective DRG, (2) gallamine administration increased spontaneous activity from DRG in chronically axotomized rats, (3) ongoing sympathetic efferent activity in rat saphenous nerve was decreased by distal axotomy for up to 8 weeks, and (4) rare branched sensory afferents occasionally exhibit spontaneous activity.

The patterns of [ 14C]2-deoxyglucose uptake in female rat brain produced by electrical stimulation of hypothalamic and limbic brain areas

The aim of this study was to investigate the pattern of [14C]2-deoxyglucose uptake in anaesthetized rat brain produced by electrical stimulation of brain areas implicated, by previous electrical stimulation studies, in the neural control of pituitary hormone and especially gonadotrophin secretion. Stimulation of the median eminence led to a significant increase in the relative metabolic activities of the arcuate, ventromedial hypothalamic, supraoptic and paraventricular nuclei and the preoptic area. Stimulation of the suprachiasmatic or paraventricular nuclei or the medial preoptic area, anterior hypothalamic area, the dorsal or ventral hippocampus or amygdala led to an increase in the relative metabolic activity of many brain regions known to have direct connections with these areas, but in addition produced increases in the relative metabolic activity of areas which have secondary connections. Hippocampal stimulation confirmed previous neuroanatomical findings of major intrinsic functional connections between different fields of the ipsilateral and contralateral hippocampus. Stimulation of the amygdala, unexpectedly, did not change the relative metabolic activity of the arcuate nucleus and medial preoptic area which have neuroanatomical connections with the amygdala. Similarly, stimulation of the medial preoptic area did not change significantly the relative metabolic activity of the mamillary body and dorsomedial thalamic area. The effect of preoptic area stimulation on the relative metabolic activity of several brain regions was changed by ovariectomy and by injection of oestradiol benzoate. Stimulation of the preoptic area and suprachiasmatic nuclei, but not the anterior hypothalamic area or other brain regions, increased significantly the plasma concentrations of luteinizing hormone. These results show that (i) electrical stimulation of brain areas concerned with the control of gonadotrophin and other pituitary hormone secretion changes the metabolic activity of nuclei and neural pathways extrinsic as well as intrinsic to the hypothalamic-pituitary system, (ii) the [14C]2-deoxyglucose method can detect changes in antidromic as well as orthodromic activity and in multi-synaptic pathways, (iii) neuroanatomical pathways are not always activated metabolically by electrical stimulation, and (iv) the preoptic-suprachiasmatic nucleus gonadotrophin control system is discrete and is little affected by increased metabolic activity of the hypothalamus produced by stimulation of the anterior hypothalamic area or other brain areas.

Segmental inhibitory response in the frog spinal cord during orthodromic motoneuron activation

Different types of reflex discharges were produced in various preparations by stimulating the dorsal root of isolated frog spinal cord. These ranged from multiphasic low-amplitude waves to distinctly synchronized monosynaptic response. The discharges were followed by facilitation in the former and deep, protracted inhibition of response to test dorsal root stimulation in the latter. When interstimulus intervals measured 40–50 msec, inhibitory action was less pronounced than at shorter (15–30 msec) or longer (60–100 msec) intervals, thus indicating that at least two types of inhibition were at work, one at an earlier and the other at a later stage. Strychnine at a concentration of 10−5 M effectively reinforced the former and blocked the latter, while 10−4 M d-tubocurarine attenuated both types of inhibition substantially. It is concluded that inhibition of response occurs mainly as a result of recurrent activation of inhibitory systems via recurrent motoneuron axon collaterals when frog spinal cord afferents are excited. Intensity of the later (presynaptic) and earlier (postsynaptic) inhibition of reflex transmission is determined by the degree of synchrony in motoneuronal discharge in response to orthodromic stimulation.

A stain for ischaemic or excessively stimulated neurons

Loyez' myelin stain sometimes impregnates the perikarya and processes of neurons. This is rare in normal adult mice, but can be provoked by various means including electrical stimulation and mild ischaemia shortly before fixation. Passing a direct current or a train of pulses across the dura of the cerebral cortex produces a patch at the site of stimulation in which the neurons, but not the glia, are Loyez-impregnated; pulse-trains evoke such impregnation even at remote sites, presumably through orthodromic and/or antidromic activation. The strength and duration of stimulation necessary to provoke impregnation are below the threshold for causing an overt lesion. Local ischaemia produced by irreversibly occluding a small subarachnoid artery for as little as 7 min evokes a small patch of impregnated neurons in the superficial layers adjacent to the occluded artery. After slightly longer-lasting (e.g. 17 min) ischaemia, the impregnated zone spans most of the cortical depth. Mild global ischaemia produced by irreversibly occluding one or both common carotid arteries 30 min before fixation causes large numbers of neurons to be impregnated in many parts of the brain. That interventions as different as electrical stimulation and arterial occlusion both lead to neuronal impregnation may most plausibly be explained by the fact that they both cause cells to be depolarized. The method will be useful for visualizing overstimulated or ischaemic neurons, and may be applicable to the tracing of neural pathways.

Significance of pacing cycle lengths in manifest entraiment of orthodromic circus movement tachycardia by ventricular pacing

The physiology of entrainment of orthodromic circus movement tachycardia (CMT) was studied using ventricular pacing during 18 episodes of induced CMT in 7 patients with atrioventricular (AV) accessory pathways. The first paced impulse was delivered as late as possible in the tachycardia cycle (mean 88 +/- 5% of the spontaneous cycle length [CL]). Entrainment was demonstrated by the following criteria: 1:1 retrograde conduction via the accessory pathway; capture of atrial, ventricular and His bundle electrograms at the pacing rate; and resumption of tachycardia at its previous rate after cessation of pacing. The number of ventricular paced impulses ranged from 5 to 14 (mean 8 +/- 3), and entrainment occurred in 2 to 7 paced cycles (mean 4 +/- 2). Orthodromic activation of a major part of the reentry circuit (manifest entrainment) was demonstrated during 9 episodes by the occurrence of His bundle electrogram preceding the first CMT QRS at the time anticipated from the last paced beat. In the 9 other episodes, persistent retrograde His bundle activation and AV nodal penetration by each paced impulse caused a delay (mean 79 +/- 25 ms) in activation of the His bundle preceding the first CMT QRS after the last paced beat. The mean pacing CL achieving manifest entrainment was 92 +/- 3% of the tachycardia CL, compared with 84 +/- 3% for retrograde AV nodal penetration (p less than 0.01). In conclusion, manifest entrainment of orthodromic CMT can be demonstrated by ventricular pacing at very long CLs; shorter CLs may cause CMT termination due to retrograde AV nodal penetration.

Responses of amygdaloid central nucleus neurons to stimulation of the insular cortex in awake rabbits

Recent evidence suggests that the amygdaloid central nucleus may contribute importantly to autonomic regulation during emotional states, possibly via both direct and indirect central nucleus efferent projections to autonomic regulatory nuclei in the lower brainstem. Additional findings suggest that the insular cortex may participate in autonomic regulatory processes, possibly by exerting an influence upon central nucleus neuronal activity via its direct projections to the central nucleus. The present experiment was conducted to determine the effects of insular cortex stimulation upon extracellularly recorded central nucleus neuronal activity in conscious, drug-free, rabbits. Satisfactory recordings were obtained from 146 central nucleus neurons. These were classified as belonging to one of six general categories on the basis of rates and patterns of ongoing discharge, responses to an auditory stimulus, and location within the nucleus. Determinations were then made as to whether each neuron could be activated antidromically from a ventrolateral mesencephalic region through which descending central nucleus projections to the lower brainstem course, and hence, whether the neuron might contribute to these projections. The activity of each neuron was then assessed during single-pulse stimulation of the region of the insular cortex demonstrated previously to project to the central nucleus. Such stimulation produced no response, an initial increase, or an initial decrease in the activity of 33%, 53% and 14% of the 146 neurons, respectively. The predominant response consisted of a single spike with a short but variable onset latency, suggesting orthodromic activation via one or a few synapses. Included among the neurons that responded to stimulation of the insular cortex in this manner were seven of 22 central nucleus neurons identified as projecting to the lower brainstem. Responses consisting of initially decreased activity most often occurred in neurons that discharged infrequently and were sensory-responsive. The results of this experiment thus provide more detailed information than was available previously regarding the pervasive influence of the insular cortex upon central nucleus neuronal activity, and provide further support for the notion that the insular cortex may participate in autonomic regulatory processes by way of its direct projections to the central nucleus.

Abolition of the orthodromically evoked IPSP of CA1 pyramidal cells before the EPSP during washout of calcium from hippocampal slices.

The complex EPSP-IPSP response of CA1 pyramidal cells to orthodromic activation of Schaffer collaterals-commissural afferent fibres was monitored during washout of Ca from hippocampal slices. The IPSP was clearly abolished before the EPSP and this occurred when the extracellular Ca([Ca2+]o) had fallen to between 1.03 and 0.7 mM. The loss of the IPSP was usually associated with a temporary increase in size of the EPSP and sometimes a membrane depolarization and the appearance of spontaneous activity. As [Ca2+]o fell further these effects were reversed and eventually the EPSP was abolished when [Ca2+]o had reached between 0.78 and 0.26 mM.

Inhibitory connections between AVCN and DCN: Evidence from lidocaine injection in AVCN

Principal cells of the dorsal cochlear nucleus (DCN) receive a variety of inhibitory influences, including some that are associated with the anteroventral cochlear nucleus (AVCN). Electrical stimulation in the caudal part of the AVCN produces long-lasting inhibition of DCN units [(1973) Exp. Brain Res. 17, 428-442], including unit type IV, which is associated with principal cells. This inhibition may be mediated either by orthodromic activation of AVCN axons that terminate in DCN or by antidromic stimulation of DCN inhibitory interneurons whose axons send collaterals to the AVCN. These two possibilities cannot be distinguished with electrical stimulation alone. In this study, microinjections of lidocaine were made in the AVCN. These injections should block AVCN to DCN axons without directly affecting the activity, within the DCN, of DCN interneurons. Two effects of lidocaine injections were observed. In some cases, all activity of DCN cells was abolished by lidocaine. These cases involved either spread of lidocaine to the recording site or into the auditory nerve. In other cases, the inhibitory responses of DCN type IV units were weakened by lidocaine without changing the units' thresholds or spontaneous activity. The latter result demonstrates that there are inhibitory pathways originating in AVCN or passing through AVCN and terminating in the DCN.