Synchronized activity of renal neurons and their pattern of discharge in rabbits.

Mechanisms of synchronization of renal neurons were studied by correlating its primary features (peak width and peak height of correlation histograms) with parameters derived from interspike-interval histograms of their resting activity. In anaesthetized rabbits the synchronous correlograms had a peak width of 210+/-8.8 ms (x+/-SEM; n=156) and their peak height was 4.3+/-2 spikes/s. Following parameters were calculated from interval-histograms of single renal units: the shortest and preferred interspike-intervals (their values were 9+/-0.5 ms and 11+/-1 ms, respectively), and longest interspike-interval and spread of histogram (amounting to 5.79+/-0.45 s and 5.76+/-0.37 s, respectively). Peak width of cross-correlogram was significantly correlated both with the longest interspike-interval (r=-0.426) and histogram spread (r=-0.431) while the strength of relationship with the shortest and preferred interspike-intervals was non-significant. On the other hand, peak height of correlograms was significantly correlated with the longest and preferred interspike-intervals (r=-0.179 and r=-0.191) and histogram spread (r=0.191). These data suggest various properties of both primary features of synchronized firing. They also support the concept of DiBona that various intrarenal effectors may be activated by single renal sympathetic neuron due to information encoded in its discharge pattern.

Functional connectivity between neurons generating resting discharge in renal sympathetic neurons in the rabbit.

In anaesthetised rabbits, we analysed the cross-correlations of resting discharges in pairs of simultaneously recorded renal neurons. The study of 428 significant cross-correlations showed three pure types of neuronal co-ordination and two combined effects. Pure shared input was observed in 202 pairs of neurons (47.2%). The width of cross-correlogram peak was 222.9 +/- 7.2 ms. The peak height of shared input was 4.8 +/- 0.2 spikes s(-1) and was significantly related with correlogram width. Pure excitatory connection was found in 24 neuronal pairs (5.6%). Its peak width was 7.9 +/- 1.9 ms and it was shifted from time zero by 13.3 +/- 3.4 ms. The amplitude of the peak was 19.6 +/- 4.6 spikes s(-1). In 165 pairs of neurons (38.6%), excitatory connection was combined with shared input component. Pure reciprocal activation was seen in only 5 pairs of neurons (1.1%) while in 32 pairs (7.5%) it was accompanied by shared input co-ordination. The distance between narrow peaks measured in the combined type of co-ordination was 32.5 +/- 3.5 ms and the mean peak height was 4.1 +/- 0.7 spikes s(-1). Shared input in pure form and that accompanying both excitatory connection and reciprocal activation were significantly related to the frequency of discharge of neurons contributing to the cross-correlogram. The incidence and basic properties of the encountered types of neural coordination may indicate a pattern of interconnections between cells generating vasomotor tone in renal sympathetic neurons.

Responses of the red nucleus neurons to stimulation of the paw pads of forelimbs before and after cerebellar lesions.

Cerebellar cortex ablation releases deep cerebellar nuclei of monosynaptic inhibition from Purkinje cells. Therefore, it strengthens excitatory influence from Interpositus Nucleus (IN) upon Red Nucleus (RN), which results in much higher facilitation of the rubro-spinal neurons. This causes a big increase of spontaneous discharge rate, and eliminates brakes of discharges from responses generated by somatosensory stimuli. These two changes destroy content and timing of feedback information flowing through the spino-cerebello-rubro-spinal loop. This false bias of the feedback information, very important for fast postural adjustment and coordination of ongoing movements executed by central motor program, may at least in part be responsible for abnormal motor behavior evoked by cerebellar damage. Hemicerebellectomy resulted in dramatically reduced spontaneous activity and responses to limb stimulation because of severing a major input to the red nucleus from deep cerebellar nuclei. Due to direct somatosensory input to magnocellular Red Nucleus (mcRN) from the spinal cord that bypassed the cerebellum, the latency of response to limb stimulation was not changed and the narrower receptive fields were still present.

Excitatory and inhibitory responses of the ongoing sympathetic discharge in single renal neurons to liminal stimulation of aortic C-fibres in the rabbit.

Excitatory and inhibitory responses of sympathetic discharge were recorded in single renal postganglionic neurons of rabbits anaesthetized with urethane and chloralose. The animals were vagotomized and had transected aortic nerves. Responses were elicited by single volleys in the aortic C-fibres. Excitatory responses consisted in short-lasting increase in the rate of ongoing sympathetic discharge and were followed by inhibitory responses. Excitatory effects together with inhibitory responses were seen in 68% of units (19/28). Only excitatory effects appeared in 2 neurons (7.1%) and only inhibitory effects in 7 neurons (25%). In renal neurons exhibiting both effects, the excitatory responses appeared after latency of 172 +/- 8 ms (x +/- S.D.) and had duration of 64 +/- 11 ms. Inhibitory effects had latency o f 257 +/- 10 ms and their duration amounted to 265 +/- 22 ms. In more than half of recordings the excitatory responses were separated from the inhibitory effects by discharge lasting 33 +/- 4 ms. Significant correlations between latencies of excitatory and inhibitory responses and between duration of excitatory and latency of inhibitory responses suggest interaction between both effects. Increase in the number of afferent volleys (1 through 5) evoked relatively small changes in duration of the excitatory effect indicating that temporal facilitation is of minor importance in generating this response. Temporal facilitation was found to play an important role in determining duration of the inhibitory response. Comparison of effects of unilateral and bilateral stimulation of the aortic C-fibres showed larger occlusion of durations of the excitatory than inhibitory responses.

Pattern of ongoing discharge of single renal sympathetic neurons in the rabbit.

Ongoing discharge in single renal sympathetic neurons was first studied in vagotomized rabbits without baroreceptor information (60 min after section of the aortic nerves). Under urethane + chloralose anaesthesia interspike-interval histograms were compiled and discharge rates were measured in 79 neurons. The following parameters were analysed: (a) the shortest, (b) the preferred and (c) the longest interspike-intervals, (d) discharge rate, (e) spread of a histogram, (f) coefficient of symmetry, and (g) coefficient of variability. The type of distribution of histograms and 9 correlations between some parameters were also assessed. These parameters were considered to make up the pattern of the ongoing discharge. The shortest, preferred and longest interspike-intervals of the ongoing discharge were: 14.1 +/- 0.9, 30.4 +/- 3.5 and 1672 +/- 82 ms. The mean rate of discharge amounted to 1.78 +/- 0.08 spikes/s. Three out of 9 correlation coefficients between the above parameters were statistically significant. In a second part, the effect of section of the aortic nerves and of 4-aminopyridine (a drug known to enhance synaptic transmission) on the pattern of ongoing discharge were also studied. Ten minutes after section of the aortic nerves the rate of discharge significantly increased, the shortest interspike-interval diminished and coefficient of variability was not changed. The number of significant correlations rose from 3 to 9.4-Aminopyridine significantly increased the discharge rate, did not alter the shortest interspike-interval and increased the coefficient of variability. These data show that assessing several parameters of ongoing discharge making up its pattern may differentiate between the excitatory effects of section of the aortic nerves and administration of 4-aminopyridine and in this way help to elucidate the mechanisms of action of various factors affecting renal sympathetic discharge.

Inhibition of renal nerve discharge by liminal stimulation of non-myelinated aortic afferents.

The pattern of inhibitory responses of sympathetic nerve discharge to liminal activation of aortic C-fibres was studied in rabbits. The animals were anaesthetized with urethane and chloralose and vagotomized. Sympathetic postganglionic discharge was recorded from single fibres of the renal nerve. Inhibitory responses were elicited by single shocks or short trains (2-5 shocks at 10 Hz) and assessed from peri-stimulus time histograms. Clear-cut inhibition of the sympathetic discharge was observed in 6 out of 10 fibres. It was evoked by one shock in 5 fibres and by two shocks in 1 fibre. The mean latency of the inhibitory response elicited by one shock was 318 +/- 18 ms and its duration amounted to 196 +/- 22 ms (mean +/- SE). The increase in the number of shocks prolonged the duration of the inhibitory response without markedly affecting their latency.

Pattern of irregular dorsal root discharge in the spinal cat.

Pattern of irregular type of dorsal root discharge (DRD) in non-anaesthetized spinal cats was inferred from the distribution of its interspike intervals. Interspike interval histograms were compiled from antidromic spike potentials of irregular DRD which were recorded in the central ends of 33 single dorsal root fibres of L7 dorsal root. The majority of histograms was unimodal. The mean preferred interval of irregular DRD which indicated the most frequently occurring interspike interval was 6.1 +/- 0.5 ms. The shortest and longest intervals were 3.7 +/- 0.3 ms and 45.9 +/- 4.4 ms, respectively. The coefficient of symmetry of the histogram was 0.06, indicating highly unsymmetrical distribution of intervals of irregular DRD. Conduction velocity of dorsal root fibres carrying irregular antidromic discharge amounted to 52.3 +/- 5.3 m/s (n = 23). There were no significant correlations between three analysed interspike intervals and conduction velocity. The results are discussed in view of the hypothesis of the modulating effect of antidromic discharge on the afferent inflow. Comparison of preferred interspike interval of irregular DRD with the existing data on the rate of orthodromic activity in afferent nerve fibres suggests that irregular antidromic discharge on many occasions is able to block othodromic impulses by collision.

Excitatory responses of the dorsal root discharge in L7 segment elicited by ascending and descending volleys in the cat.

Excitatory responses of the dorsal root discharge (DRD) which consist in short-lasting increase in its frequency have been recorded from the central cut ends of single dorsal root fibres of L7 dorsal root in spinal cats. They were evoked by stimulation of afferent nerves entering the cord below and above the level of recording of antidromic discharge and then ascending and descending to this level. Ascending volleys were provided by stimulation of caudal femoral posterior and pudendal nerves and descending volleys by stimulation of saphenous and quadriceps nerves. The excitatory responses of the DRD were elicited by stimulation of low threshold cutaneous afferents and group II and III muscle afferents while high threshold cutaneous and group I muscle afferents were ineffective. The excitatory responses of the DRD evoked by ascending volleys were larger than the effects elicited by descending volleys. The incidence of the excitatory effects to ascending volleys was significantly higher than to descending volleys. The size and incidence of the excitatory responses to ascending and descending volleys were, however, smaller than those of the effects elicited by stimulation entering the cord at the level of recording of antidromic discharge (i.e. in the posterior tibial nerve). It is suggested that the size and incidence of the excitatory responses of the DRD are related to the direction of spread and the level of entry of afferent volleys.

Excitatory responses of the dorsal root discharge to stimulation of cutaneous and muscle afferents in the cat.

Excitatory responses of the dorsal root discharge (DRD) consisting in transient increase in its frequency have been studied in non-anaesthetized low spinal cats. They were evoked by stimulation of cutaneous nerves (superficial peroneal and posterior tibial) and muscle nerves (gastrocnemius-soleus and posterior biceps-semitendinosus), recorded from the central cut ends of single fibres of L7 dorsal roots. The excitatory responses were elicited by single volleys in low threshold cutaneous and group II muscle afferents. Group III afferents of gastrocnemius-soleus nerve were also effective. Increase in strength of stimulation of posterior biceps-semitendinosus nerve from 4T to 40T which activated group III muscle afferents significantly decreased the excitatory effects of the DRD. Incidence of excitatory responses of the DRD to volleys both in low and high threshold cutaneous afferents, was 100%. Frequency of occurrence of excitatory effects to volleys in group II muscle afferents ranged from 23% to 43% (for responses to posterior biceps-semitendinosus and gastrocnemius-soleus volleys, respectively). It was increased to 47% and 72% when excitatory effects were elicited by group III afferent volleys. These findings indicate that only some types of afferent fibres evoke excitatory responses of the DRD. Variable incidence of the excitatory responses to stimulation of cutaneous and muscle afferents suggests important difference in effectiveness of connections between both types of fibres and interneurones generating the DRD.

Long-lasting depolarization of the central terminals of cutaneous afferents in L7 segment evoked by volleys ascending from the sacral cord in the cat.

1. In 72% of non-anaesthetized spinal cats, single volleys ascending from the sacral cord evoke long-lasting primary afferent depolarization in L7 segment. It occurs in the central terminals of cutaneous but not in Ia muscle afferents. 2. Volleys descending to L7 segment evoke only short-lasting presynaptic depolarization. 3. It is concluded that presynaptic inhibition in L7 segment produced by ascending volleys is more effective than that evoked by descending volleys.

Interactions between inhibitions of sympathetic nerve discharge to successive stimulations of baroreceptor and cutaneous afferents.

Interactions between inhibitions of sympathetic nerve discharge (SND) to consecutive stimulations of A- and C-fibres in the aortic nerve and superficial peroneal (SP) nerve have been studied in rabbits anaesthetized with urethane and chloralose. SND was recorded from the renal nerve. At interval of 10 s following conditioning stimulation of SP nerve the test response of SND to activation of C-fibres (interaction SP-C) amounts to 83.7 +/- 7.5% (means +/- SE) of control. After applying both stimulations to the same SP nerve (interaction SP-SP) the test response of SND is significantly lower amounting to 56.3 +/- 3.9%. Comparable decrease of the effect of conditioning stimulation of one type of afferents on the test response to activation of other type of fibres was observed at interval of 10 s in two other interactions (SP-A and C-A). In seven interactions the conditioning stimulation of one type of fibres had no effect on the test response to stimulation of other type of fibres. This was found in one interaction at interval of 10 s (C-SP), in four interactions at interval of 20 s (SP-A, C-SP, SP-C and C-A) and in two interactions at interval of 40 s (SP-A and SP-C). Conditioning stimulations used in above interactions depressed the test responses to activation of the same type of fibres. It is suggested that the decrease or suppression of the effect of conditioning stimulation of one type of afferents on the test response of SND to activation of other type of fibres is related to disinhibition of this response.

Conditioning of inhibition of sympathetic nerve discharge to stimulation of A- and C-fibres in the aortic nerve.

Stimulation of either A- or C-fibres in the aortic nerve inhibits sympathetic nerve discharge (SND) recorded from the renal nerve in rabbits anaesthetized with urethane. When the test inhibition of SND to stimulation of A-fibres is preceded by conditioning stimulation of the same afferents, the test response is depressed at shorter and facilitated at longer testing intervals. Facilitation of the inhibition of SND reaches 120% of control at a testing interval of 10 s. The recovery curve of inhibition of SND to activation of A-fibres has a time course of 17 s. Following conditioning activation only depression of the test inhibition of SND to stimulation of C-fibres is seen. It reaches 46% of control at an interval of 2 s and the recovery curve of inhibition of SND to stimulation of C-fibres has a time course of about 30 s. In other series of experiments the duration of the conditioning stimulation was varied while the testing intervals were fixed. At a testing interval of 2 s the reductions of the test responses are deeper and the durations of conditioning at which plateaus of depression are reached are longer with stimulation of C- than of A-fibres. Taken together with a longer recovery curve these findings suggest a more effective control of the test inhibition of SND by C-fibres. Opposite changes in the patterns of inhibition of SND to activation of either A- or C-fibres are explained by frequency-dependent post-tetanic effects of the conditioning stimulation.

Distribution of bilateral dorsal root potentials evoked by volleys in afferents entering lumbar and sacral segments of the spinal cord.

Ipsilateral dorsal root potentials evoked by volleys entering lumbar and sacral segments of the cord are largest at the level of entry of afferent volleys. Contralateral potentials resulting from stimulation of any of these nerves attain maximum amplitude in lower sacral and upper caudal segments.

Differential decerebrate control of depolarization in the central terminals of cutaneous afferents in the sacral cord.

Presynaptic depolarization of cutaneous afferents has been investigated in the sacral cord of decerebrate cats before and after spinal cord transection. In the decerebrate state the central terminals of caudal femoral cutaneous nerve are depolarized by ipsilateral volleys entering the cord via sacral and lumbar dorsal roots. A significant increase of depolarization occurring after severing the cord indicates that there is tonic decerebrate inhibition of presynaptic depolarization in terminals of caudal femoral cutaneous nerve. In contrast to this finding, presynaptic depolarization evoked in the central terminals of the pudendal nerve by ipsilateral volleys entering the cord through sacral and lumbar dorsal roots is not subjected to decerebrate inhibitory control. It is suggested that differential inhibitory control of depolarization in the central terminals of cutaneous nerves in the sacral cord is related to the intraspinal course of their fibres, to differences in the receptor types involved, and to the location of their innervation fields. In more than half of the decerebrate preparations stimulation of the central terminals of cutaneous afferents through microelectrodes evokes antidromic spikes appearing simultaneously in ipsi- and contralateral nerves. The time course of bilateral excitability changes is similar on both sides of the cord. It is assumed that presynaptic effects are transmitted to the contralateral side by collaterals of ipsilateral cutaneous afferents.

Hyperpolarizing dorsal root potentials recorded from single fibres of the dorsal root in the cat.

In non-anaesthetized spinal cats hyperpolarizing dorsal root potentials (DRPs) were recorded from single fibres of the dorsal root. They were evoked by volleys in saphenous and quadriceps nerves activating group II muscle afferents and cutaneous A afferents. Hyperpolarizing DRPs were most frequently encountered in fibres originating from muscle receptors. Their frequency was lower in fibres from deep receptors, from low threshold mechanoreceptors and from mechanical nociceptors. The amplitude of hyperpolarizing DRP was related to the modality of fibres from which DRP was recorded. During conditioning the time course of depression of testing hyperpolarizing DRP recorded from muscle receptor fibres did not exceed 100 msec. Hyperpolarization produced by repetitive stimulation was maintained in muscle afferent fibres but subsided to zero in fibres from low threshold mechanoreceptors.

Maintained depressor responses evoked by continuous and intermittent stimulation of aortic nerve in the rabbit.

Stability of depressor responses evoked by long-lasting continuous and intermittent stimulation of the aortic nerve was studied in rabbits anaesthetized with urethane. Continuous stimulation produces blood pressure falls whose stability at low frequencies (1-10 cycles/sec) ranges from 91 to 86%. With rise of the stimulation frequency stability is decreased : at 500 cycles/sec, it amounts to 19%. Intermittent stimulation consisting in switching excitation on and off every 10 sec increases stability of depressor responses and at 500 cycles/sec, it is significantly higher than stability of effects produced by continuous stimulation. Following transection of aortic nerves, stability is increased at all frequencies of continuous stimulation and at all but the lowest frequency of intermittent stimulation. Vagotomy performed after section of the aortic nerves does not significantly affect the changes in stability observed after severing the aortic afferents. It is suggested that at high frequencies of stimulation, stability of depressor responses is reduced by homosynaptic depression. During intermittent stimulation, its effect is counteracted by post-tetanic changes occurring at intervals when the stimulation is switched off. The increase in stability after section of aortic nerves is probably related to its effect on excitability of the vasomotor centres.

Recurrent inhibition of the monosynaptic reflex in the upper caudal cord of the cat.

In spinal cats both ipsi- and contralateral antidromic volleys in the 3rd sacral ventral roots produce recurrent inhibition of the monosynaptic reflex evoked by stimulation of the 1st caudal dorsal root and recorded from the corresponding ventral root.