Effects of stimulating midbrain central gray matter on neuronal response in the caudal trigeminal nucleus to peripheral nerve stimulation

Stimulating the midbrain central gray matter (CGM) with trains of 10–20 stimuli was found to inhibit response to electrical stimulation of infraorbital nerve and tooth pulp A-alpha and A-delta afferents at 100 msec intervals in 65% of the caudal trigeminal nucleus in neurons tested during experiments on cats under chloralose-Nembutal anesthesia. Response was inhibited most effectively in convergent neurons (activated by stimulating infraorbital nerve and tooth pulp A-alpha and A-delta afferents) to stimulating tooth pulp (0.76) and, to a somewhat lesser degree, to stimulation of A-alpha afferents (0.6). For high-threshold neurons (activated by stimulating infraorbital nerve and tooth pulp A-delta afferents), success rate of inhibiting response under the effects of CGM stimulating measured 0.71 and 0.48 for low-threshold cells (activated by stimulating infraorbital nerve A-alpha afferents). Stimulating CGM produced an excitatory response in 10 caudal trigeminal nucleus neurons within 7.5–20 msec; after this neurons showed no reaction to peripheral nerve stimulation for a 200–450 msec period. The possible involvement of these neurons in pressing the mouth-opening reflex produced by CGM stimulation is discussed in this article.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 20, No. 6, pp. 729–736, November-December, 1988.     

Effects of stimulating the midbrain central gray matter on neuronal response in the cat ventroposteromedial thalamic nucleus

The effects of stimulating the midbrain central gray matter (CGM) on neuronal response in the ventroposteromedial (VPM) nucleus produced by stimulating tooth pulp, A-alpha and A-delta fibers of the intraorbital nerve and the caudal nucleus of the spinal trigeminal tract (CN STT) were investigated during experiments on cats under thiopental-chloralose anesthesia. It was found that applying trains of stimuli to the CGM produced excitatory responses in a proportion of the test neurons with latencies of up to 30 msec. Application of conditioning stimulus to the CGM led to suppression of response of efferent stimulation in neurons belonging to low-threshold, convergent, and high-threshold groups. Responses produced in 40% of neurons by stimulating tooth pulp and A-delta fibers of the suborbital nerve, as well as those evoked in 26.4% of thalamic VPM cells by stimulating A-alpha fibers of the suborbital nerve were completely suppressed. The inhibitory effect found when stimulating CGM on response in certain neurons, produced by stimulating both the peripheral nerve and the CN STT, would indicate that the CGM could exert an influence on the activity of thalamic VPM neurons directly.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 20, No. 5, pp. 688–694, September–October, 1988.     

Effects of stimulating the central gray matter on neuronal response in the cat medial thalamic nuclei

This study was performed on the effects of stimulating the midbrain central gray matter (CGM) on neuronal response in the association medial thalamic nuclei evoked by stimulation of A-alpha and A-delta fibers of the infraorbital nerve and the caudal nucleus of the spinal trigeminal tract (CN STT) and tooth pulp stimulation using cats anesthetized by thiopental-chloralose as experimental animals. Stimulating the CGB with trains of stimuli was found to evoke an excitatory response in a percentage of the neurons tested, in which latency fluctuated between 15 and 40 msec. Applying conditioned stimuli to the CGM caused suppression of response to afferent impulses in neurons belonging to the "convergent" and "low" and "high" threshold groups. Responses induced by stimulating tooth pulp and A-delta fibers showed 100% inhibition as compared with 86% during A-alpha fiber and infraorbital nerve stimulation. The fact that stimulating the CGM produces an inhibitory effect on the response of thalamic neurons evoked by stimulation of both peripheral afferents and the CN STT would indicate that the CGM can exert a direct action on thalamic neuronal activity.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 19, No. 5, pp. 660–665, September–October, 1987.     

Suppression of postsynaptic response in trigeminal motoneurons by stimulating the midbrain central gray matter

The effects of stimulating the midbrain central gray matter (CGM) on motoneuronal response in trigeminal nerves were investigated in anesthetized cat. It was found that stimulating the CGM did not induce postsynaptic response in these motoneurones. Conditioning stimulation of the CGM brought about suppression of motoneuronal postsynaptic response to stimulation of tooth pulp and high threshold infraorbital nerve afferents without affecting motoneuronal antidromic response and jaw-opening reflex as induced by stimulating the caudal nucleus of the spinal trigeminal tract. It was thus concluded that stimulating the CGM exerts no direct effect on motoneurons but does have an influence on postsynaptic response — a result of modulation of the afferent spike flow at interneuronal level.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 22, No. 4, pp. 543–549, July–August, 1990.     

Effects of stimulating the periaqueductal gray matter on high- and low-threshold startle reflexes

The effects of stimulating the periaqueductal gray matter (PAG) on two types of startle reflex (spino-bulbo-spinal reflex produced by intensive stimulation of the peripheral nerves and low-threshold tactile spino-reticulo-spinal reflex) as well as high-threshold jaw-opening reflex arising in response to tooth pulp stimulation were investigated in cats anesthetized with chloralose. Simulating most PAG test sites led to pronounced inhibition of jaw-opening reflex, profound depression of spino-bulbo-spinal reflex, and moderate inhibition of tactile reflexes. The facilitatory effect of stimulating a number of PAG sites on the latter reflexes was demonstrated. Effects of PAG stimulation fell into two classes: brief, measurable in hundreds of msec and more prolonged, measured in minutes and seconds. Findings would indicate certain differences between the effects of PAG stimulation low-threshold (non-nociceptive) and high-threshold (nociceptive) startle reflexes, of which the possible mechanisms are discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 21, No. 1, pp. 71–78, January–February, 1989.     

Effect of electroacupuncture on the activity of neurons in the central gray matter of the midbrain

The effect of electroacupuncture in locally-segment and general analgetic points on background impulse activity of central gray substance neurons and their activity caused by nociceptive stimulation of the dental pulp, infraorbital nerve and forearm skin surface was studied in acute experiments on cats. It has been established that general analgetic points are better represented in the central gray substance, as compared to locally-segment points. Different degree involvement of central gray substance in the realization of acupuncture analgetic effect in different points is postulated. The role of dorsal and ventral compartments of the central gray substance in acupunctural analgesia is discussed.     

Role of the serotoninergic system in inhibition of jaw-opening reflex induced by stimulating the midbrain central gray matter

The effects were studied in waking cats of brief stimulation (20 stimuli at a rate of 400 Hz) of the central gray matter (CGM) and dorsal raphe nucleus (DRN) on high-threshold jaw-opening reflex (HJOR) evoked by tooth pulp stimulation during blockade of serotonin synthesis produced by application of 300 mg/kg parachlorophenylalanine (PCPA) i.p. Inhibitory effects of CGM and DRN stimulation had already declined in comparison with post-stimulation (but pre-PCPA) level within 24 h after PCPA application; 96 h afterwards, inhibition of HJOR induced by CGM and DRN stimulation had become only minimal: amplitude of the reflex had declined to 30–35% and duration of inhibitory effects ws 200–250 msec. It is therefore deduced that serotonin contributes to the HJOR depression induced by CGM and DRN stimulation and the possible involvement of other neuromodulators in this effect is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 21, No. 1, pp. 45–52, January–February, 1989.     

Effects of aspartate,substance P,and serotonin on neuronal activity in the central gray substance:In vitro experiments

Effects of aspartate (2 · 10^–5 M), substance P (10^–7–10^–8 M), and serotonin (5-hydroxytryptamine, 5-HT; 5 · 10^–5 M) on the background activity of neurons in the central gray substance (CGS) were studied on slices of the rat midbrain. Aspartate and substance P (transmitters of nociceptive signals), and 5-HT (modulator of transmission of nociceptive influences) were found either to facilitate or to depress the activity of CGS neurons. The predominant effect of substance P or 5-HT applications to neurons of the dorsal CGS part was facilitation, and to neurons of the ventral CGS part, inhibition. The effects of aspartate application on studied CGS neurons were of varying nature, but inhibitory effects were found to prevail.The findings support our earlier hypothesis that assigned the studied neurons to spontaneously discharging inhibitory CGS interneurons, which control the activity of efferent CGS neurons. The role of tested substances in the regulation of CGS neuronal activity and the antinociceptive CGS effects is discussed.Neirofiziologiya/Neurophysiology, Vol. 25, No. 5, pp. 354–362, September–October, 1993.     

Effects of lordosis-relevant neuropeptides on midbrain periaqueductal gray neuronal activity in vitro.

Certain neuropeptides can facilitate lordosis by acting on midbrain periaqueductal gray (PAG) in estrogen-primed female rats. Here, we investigated responses of individual PAG neurons in vitro, to five neuropeptides: substance P (SP), luteinizing hormone-releasing hormone (LHRH), prolactin (PRL), oxytocin (OT), and thyrotropin-releasing hormone (TRH). Substance P, OT, and TRH excited spontaneous activity of PAG neurons through neurotransmitter-like actions in a dose-dependent manner, whereas LHRH and PRL virtually never affected PAG neurons this way. Oxytocin acted through oxytocin receptors located on the recorded PAG neurons, since excitatory actions of OT were 1) not abolished by synaptic blockade, 2) mimicked by the OT-specific agonist [Thr4, Gly7]OT but not by arginine vasopressin, and 3) blocked by the OT-specific antagonist [d(CH2)5,Tyr(Me)2,Orn8]vasotocin. Although LHRH had no neurotransmitter-like action on spontaneous activity of PAG neurons, it, as well as SP, could modulate responses of some dorsal PAG neurons to GABAA and GABAB agonists or norepinephrine. Neuromodulatory actions of LHRH and SP could help facilitate lordosis through PAG neurons.     

Comparative effects of amygdala and central gray matter of the midbrain on lateral hypothalamic unit activity

The effect of stimulation of the stria terminalis, the main afferent component of the amygdalo-hypothalmic system, and of the central gray matter and tegmentum of the midbrain on lateral hypothalamic unit activity was investigated in acute experiments on rats. Five types of unit responses were discovered: phasic excitation and inhibition, tonic activation and inhibition, and a biphasic response. In response to stimulation of the stria terminalis and lateral hypothalamus mainly inhibitory responses (62.7%) were recorded. As a result of stimulation of the central gray matter most lateral hypothalamic neurons (87%) were activated. Convergence of influences from the amygdala and tegmentum was observed on 14.4% of responding neurons. The structures had an antagonistic action on most (84.6%) of the lateral hypothalamic neurons tested.Institute of Physiology, Siberian Branch, Academy of Medical Sciences of the USSR, Novosibirsk. Translated from Neirofiziologiya, Vol. 9, No. 1, pp. 25–32, January–February, 1977.     

Effect of stimulation of the amygdala and subthalamus on unit activity of the mesencephalic central gray matter

Characteristics of unit activity of the mesencephalic central gray matter were studied during electrical stimulation of the amygdala and subthalamus (chiefly the zona incerta) in acute experiments on rats. Stimulation of the amygdala evoked chiefly inhibitory unit responses (72%), whereas stimulation of the zona incerta evoked chiefly excitatory responses (59%). The effectiveness of regular (5 Hz) stimulation of the amygdala in producing prolonged changes in unit activity was noted and points to the modulating character of the influence of this structure on the central gray matter. In 31 of 114 neurons tested convergence of impulses from the amgydala and zona incerta was observed. The two types of stimulation most frequently induced inhibition (71%).Institute of Physiology, Siberian Branch, Academy of Medical Sciences of the USSR, Novosibirsk. Translated from Neirofiziologiya, Vol. 10, No. 3, pp. 245–251, May–June, 1978.     

Excitation and inhibition of neurons in the trigeminal nucleus caudalis following periaqueductal gray stimulation

Electrical stimulation (3-4 shocks, 300 Hz, 30-150 microamperemeter) of the periaqueductal gray matter (CG) or dorsal raphé nucleus (DR) of decerebrate cats reduced or abolished the jaw-opening reflex response evoked by stimulation of either the tooth pulp or infraorbital nerve. In addition, CG or DR stimulation inhibited the response of 12 out of 16 trigeminal nucleus caudalis neurons to activation of their sensory afferent inputs. Ten other neurons recorded in the same sites, and often at the same time, but which did not respond to the sensory inputs utilized, were excited by identical stimuli to CG or DR. This excitatory response was blocked by intravenously administered naloxone (0.1-0.2 mg/kg). It is suggested that those neurons which are excited by CG and DR stimulation may be interneurons involved in pre- and post-synaptic inhibition of sensory transmission during stimulus-produced or narcotic analgesia.     

Effects of partial bulbar section on inhibition of jaw-opening reflexes induced by central gray matter stimulation in the cat

The effects of severing the spinal trigeminal tract and its caudal nucleus on high-threshold jaw-opening reflex elicited by tooth pulp stimulation were investigated during experiments on cats under chloralose-Nembutal anesthesia. Low-threshold jaw-opening reflex produced by stimulating the A--infraorbital nerve at an intensity 2–3 thresholds in relation to the most excitable fibers on this nerve was also observed, as well as suppression of these reflexes induced by central gray matter stimulation. It was found that spinal trigeminal tract section produces a 8–52% increase in high-threshold reflex. The amplitude of low-threshold reflex either remained unchanged or showed a slight tendency to rise or fall. Brief stimulation of the central gray matter produced a 100% decrease in high-threshold reflex in intact animals compared with a 40–60% decrease after section of the trigeminal tract. Protracted stimulation of the central gray brought about an 80% decline in high-threshold reflex in intact animals as against 25–30% after section. The degree to which brief stimulation of the central gray produced depression of low-threshold stimulation remained unchanged by trigeminal tract section. Protracted stimulation of the central gray matter brought about a 25–50% reduction in low-threshold reflex in intact animals and a reduction of 75% in three animals and 15–20% in four animals. This implied that the caudal nucleus of the spinal trigeminal tract exerts a more substantial influence on the process of high- than low-threshold reflex inhibition when the central gray matter is stimulated.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 19, No. 3, pp. 362–368, May–June, 1987.     

Effects of experimentally induced deficiency of catecholaminergic transmission on neuronal activity in the ventrolateral thalamic nucleus

Background activity was investigated in 272 neurons of the ventrolateral thalamic nucleus (VLTN) before and after systemic administration of neuroleptics (haloperidol and droperidol) at cataleptic doses by means of extracellular techniques during chronic experiments on cats. Autocorrelation and spectral analysis revealed regularly-occurring changes in the background activity rate of VLTN neurons, the periodicity of which changed by fractions of seconds (0.2–0.8 sec), seconds (1.5–10 sec), or tens of seconds (12–30 sec). While numbers of neurons with individual types of periodic activity did not exceed 6–8% in intact animals, it did increase to 18–30% after administering neuroleptics. Raised numbers of neurons with two types of regularly occurring processes within a single spike train were also noted. Experimentally-produced data were compared with findings from clinical observations. Quantities of neurons with different variations in the periodicity of their firing activity reached 19–46% in patients with parkinsonism but did not exceed 4–8% in those with torsion dystonia. The genesis of raised rhythmic firing in thalamic neurons occurring with parkinsonism is thought to be associated with impaired catecholaminergic (both dopaminergic and -adrenergic) transmission.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 22, No. 3, pp. 359–368, May–June, 1990.     

Effects of systemic injection of neuroleptics on neuronal background activity in the cat ventrolateral thalamic nucleus

Background activity was recorded in 272 neurons of the ventrolateral thalamic nucleus before and after systemic haloperidol and droperidol injection at a cataleptic dose using intracellular techniques during chronic experiments on cats in a drowsy condition. Brief burster discharges lasting 5–50 msec and following on at a high intraburst spike rate (of 200–450 Hz) were characteristic of neuronal activity in intact animals. Regular discharges occurred at the rate of 2–2.5 Hz or occasionally 3–4 Hz in 15% of cells. Numbers of neurons with the latter activity pattern rose to 22 and 30%, respectively, following haloperidol and droperidol injection. Both irregular and prolonged (80–300 msec) regular discharges were recorded in one third of the total. A relatively low intraburst spike rate (of 60–170 Hz) was observed in 37% of cells following 10 days' haloperidol injection. These changes are thought to be produced by intensified inhibitory effects on neurons of the thalamic ventrolateral nucleus from the substantia nigra and reticular thalamic nucleus following blockade of dopaminergic and -adrenergic receptors.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 21, No. 5, pp. 675–685, September–October, 1989.     

Effects of orexins/hypocretins on neuronal activity in the paraventricular nucleus of the thalamus in rats in vitro

Orexin-A (ORX-A) and orexin-B (ORX-B), also called hypocretin-1 and hypocretin-2, respectively, act upon orexin 1 (OX1R) and orexin 2 (OX2R) receptors, and are involved in the regulation of sleep-wakefulness and energy homeostasis. Orexin neurons in the lateral hypothalamic perifornical region project heavily to the paraventricular nucleus of the thalamus (PVT), which is deeply involved in the control of motivated behaviors. In the present study, electrophysiological and cytosolic Ca2+ concentration ([Ca2+]i) imaging studies on the effects of ORX-A and ORX-B on neurons in the PVT were carried out in rat brain slice preparations. ORX-A and/or ORX-B were applied extracellularly in the perfusate. Extracellular recordings showed that about 80% of the PVT neurons were excited dose-dependently by both ORX-A and ORX-B at concentrations of 10(-8) to 10(-6)M, and the increase in firing rate was about three times larger for ORX-B than for ORX-A at 10(-7)M. When both ORX-A and ORX-B were applied simultaneously at 10(-7)M, the increase in firing rate was almost equal to that of ORX-B at 10(-7)M, suggesting that the PVT neurons do not show a high affinity to ORX-A which is expected if they have OX1R receptors. The excitatory effect of ORX-B was seen in low Ca2+ and high Mg2+ ACSF as well as in normal ACSF, and the increase in firing rate was greater in low Ca2+ and high Mg2+ ACSF than in normal ACSF. [Ca2+]i imaging studies demonstrated that [Ca2+]i was increased in about 50% of the PVT neurons by both 10(-7)M ORX-A and ORX-B with a stronger effect for ORX-B, and the increase in [Ca2+]i induced by ORX-B was abolished in Ca2+-free ACSF, suggesting that ORX-B does not release Ca2+ from intracellular Ca2+ stores. Subsequent whole cell patch clamp recordings revealed that an after hyperpolarization seen following each action potential in normal ACSF disappeared in Ca2+-free ACSF, and the mean magnitude of the depolarization induced by ORX-B was same in normal, Ca2+-free and TTX-containing Ca2+-free ACSFs. Furthermore, ORX-B-induced depolarization was reversed to hyperpolarization when membrane potential was lowered to about -97 mV, and an increase of extracellular K+ concentration from 4.25 to 13.25 mM abolished the ORX-B-induced depolarization, indicating that the ORX-B-induced depolarization is associated with an increase in the membrane resistance resulting from a closure of K+ channels. These results suggest that orexins depolarize and excite post-synaptically PVT neurons via OX2R receptors, and that orexin-activated PVT neurons play a role in the integration of sleep-wakefulness and energy homeostasis, and in the control of motivated behaviors.     

Neurite growth-inhibitory activity in the adult rat cerebral cortical gray matter

Axon growth-promoting and -inhibitory molecules are likely to work in concert to promote and guide axons in vivo. In adult mammals, inhibitory molecules associated with myelin in the white matter of the central nervous system (CNS) play an important role in the failure of long-distance axon regeneration. The presence of neurite growth-inhibitory molecules in the adult rat gray matter has not been extensively studied. In this article we describe work on the characterization of neurite growth-inhibitory activity in the adult rat cerebral cortical gray matter using various biochemical and cell culture approaches. We show using a neuronal cell line (NG108–-15 cells) that neurite growth-inhibitory activity is present in membrane preparations of the cortical gray matter. Purified gray matter membranes also induce growth cone collapse of cultured embryonic rat dorsal root ganglion neurons. The inhibitory activity in the membrane preparations is extractable with 3-[(3-cholamidoprophyl)-dimethylammonio]-1-propane-sulfonate, but does not appear to be depleted by various lectins. Western blots and enzyme treatments showed that the inhibitory effect of the gray-matter preparations is not likely to be mediated by myelin-associated inhibitors or chondroitin sulfate proteoglycans. However, tenascin was detected in these samples and may contribute to some of the inhibitory activity. Selective separation of the inhibitory molecules can be achieved by ion-exchange chromatography, which also suggests the presence of multiple inhibitors in cortical gray matter membranes. © 1997 John Wiley & Sons, Inc. J Neurobiol 32 : 671–683, 1997