Stimulation Of Reticular Formation Research Articles

Bulbospinal inhibition of PAD elicited by stimulation of afferent and motor axons in the isolated frog spinal cord and brainstem.

1. In the isolated spinal cord and brainstem of the frog, stimulation of the brainstem (BS) with trains of 3-4 pulses at 60-400 Hz produced dorsal root potentials (DRPs). The lowest threshold sites eliciting DRPs were located at the level of the obex up to about 2.5 mm rostrally, 0.5-1.2 mm laterally, between 0.5 and 1.6 mm depth. This region corresponds to the bulbar reticular formation (RF). 2. Stimulation of the RF with strengths below those required to produce DRPs, very effectively inhibited the DRPs produced by stimulation of a neighboring dorsal root (DR-DRPs) as well as the DRPs produced by antidromic stimulation of the central end of motor nerves (VR-DRPs). The inhibition was detectable 20 ms after the first pulse of the conditioning train, attained maximal values between 50 and 100 ms and lasted more than 250 ms. 3. Stimulation of the bulbar RF increased the negative response (N1 response) produced in the motor pool by antidromic activation of motoneurons. The time course of the facilitation of the N1 response resembled that of the reticularly-induced inhibition of the VR-DRPs and DR-DRPs. 4. The present series of observations supports the existence of reticulo-spinal pathways that are able to inhibit the depolarization elicited in afferent fibers by stimulation of other afferent fibers or by antidromic activation of motor axons. This inhibition appears to be exerted on the PAD mediating interneurons and is envisaged as playing an important role in motor control.

Strychnine blockade of the non-reciprocal inhibition of trigeminal motoneurons induced by stimulation of the parvocellular reticular formation

Stimulation of a region within the parvocellular medullary reticular formation (PcRF) that contains somas of premotor interneurons produces short latency inhibitory synaptic potentials (IPSPs) in cat trigeminal motoneurons. The present study was undertaken to determine whether glycinergic synapses are responsible for these IPSPs. The intravenous administration of strychnine, an established glycine antagonist, abolished these PcRF-IPSPs. This effect appears to be specific for glycinergic inhibitory synapses because the short lasting component of the IPSP produced by inferior alveolar nerve (IAN) stimulation was also abolished, whereas, in contrast, the long lasting non-glycinergic component of this IPSP was not suppressed. These results indicate that a glycinergic system in the reticular formation is responsible for the non-reciprocal postsynaptic inhibition of trigeminal motoneurons.

Identification of the midbrain locomotor region and its relation to descending locomotor pathways in the Atlantic stingray, Dasyatis sabina

The midbrain locomotor region (MLR) in the Atlantic stingray, Dasyatis sabina, was identified and characterized. Stimulation (50–100 μA, 60 Hz) of the midbrain in decerebrated, paralyzed animals was used to elicit locomotion monitored as alternating activity in nerves innervating an antagonist pair of elevator and depressor muscles. Effective sites for evoking locomotion in the midbrain included parts of several nuclei: the caudal portion of the interstitial nucleus of the medial longitudinal fasciculus and the caudomedial parts of the cuneiform and subcuneiform nuclei. This region did not include the red nucleus, any parts of the optic tectum or the medial or lateral mesencephalic nuclei. Electrical stimulation in the MLR evokes locomotion in either the ipsi- or contralateral pectoral fin, wheres stimulation in the medullary reticular formation evokes locomotion only in the contralateral fin. Lesion experiments were performed to identify the location of descending pathways from the midbrain to the medullary reticular formation. To abolish locomotion evoked by electrical stimulation in the MLR, the medial reticular formation in the rostral medulla had to be lesioned bilaterally, or the ipsilateral medial medullary reticular formation and fibers projecting from the MLR to the contralateral midbrain had to be disrupted. Injections of HRP into the magnocellular/gigantocellular reticular formation confirmed that this area received bilateral projections from the MLR. The MLR of the Atlantic stingray appears to be similar to the lateral component of the mammalian MLR and to the MLR in other non-mammalian vertebrates.

Trigeminal nociceptive neurons in the subnucleus reticularis ventralis. II. Ascending projection

Ascending projection of trigeminal nociceptive neurons in the subnucleus reticularis ventralis (SRV) was studied in urethane/chloralose-anesthetized cats. Thalamic neurons having complex trigeminal receptive fields similar to those of SRV neurons were found in the intralaminar nuclei, i.e. nuclei centralis lateralis, centralis medialis and parafascicularis. About half of the SRV units tested were antidromically activated by electrical stimulation of the nucleus centralis lateralis. It was also found that a significant proportion of SRV units was antidromically activated by electrical stimulation of the mesencephalic reticular formation (MRF), and retrogradely labelled neurons were found in the SRV after HRP injection into the MRF. These findings suggest that SRV neurons relay trigeminal nociceptive inputs directly or indirectly via the MRF to the intralaminar nuclei.

Functional mapping of the rat brain during vocalizations: a 2-deoxyglucose study

Autoradiographic [ 14C]2-deoxyglucose (2-DG) procedures were used to map the functional activity in the CNS during vocalizations elicited by electrical stimulation of the midbrain reticular formation (MRF) in behaving rats. Following injection of 2-DG, rats received MRF stimulation through stainless steel electrodes over 90 min. Yoked controls received 2-DG injection followed by playback of the recorded vocalizations. Relative differences in peak isotope uptake (gray/white matter ratios) in 22 structures related to vocalization were compared between the two groups. The major findings were localized to hypothalamus, midbrain and brainstem structures. Significant increases in 2-DG uptake were noted in the following structures in MRF stimulated rats: dorsolateral central gray (PAG), MRF, lateral hypothalamus (LH), ventromedial hypothalamus (VmH), paraventricular nucleus (PVN) and nucleus ambiguus (NA). Cortical structures were not activated during MRF stimulation. The PAG and NA are known to be important relays in the production of vocalizations. MRF stimulation, therefore, activates the motor output pathways for vocalization, but does not appear to activate cortical and limbic motivational centers.

Instrumental conditioning of skin potential responses in curarized cats: non specific effects of a punishment procedure.

This study evaluates the effects of a punishment paradigm upon electrodermal activity (EDA) in curarized cats. In ten experimental subjects, any skin potential response (SPR) exceeding threshold value was punished by an electric shock. Ten control subjects received an electric shock or an electric stimulation of the mesencephalic reticular formation unrelated to the EDA. The results show that: a) No significant modifications of EDA occurred in subjects characterized by low initial activity; b) The frequency of SPR significantly decreased in high activity subjects used both for the experiments and the controls. Therefore, this diminution, in experimental subjects, cannot be due to a learning process. Neither can it be related to level of curarization or to rate of artificial ventilation. It is suggested that this effect results from a non-specific cortical inhibitory mechanism acting on the reticular activating system. The results obtained in three decorticated cats submitted to a punishment procedure are in accordance with such an hypothesis. Consequently the existence of operant autonomic learning remains unproven.

Effects of GABA A and GABA B receptor agonists on reticular-elicited hippocampal rhythmical slow activity

Hippocampal rhythmical slow activity (RSA) can be elicited by stimulation of the midbrain reticular formation. All classes of anxiolytic drug so far tested reduce the frequency of this RSA. Anxiolytic barbiturates and benzodiazepines, as opposed to compounds such as buspirone, are thought to act as receptor agonists of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). In the present study muscimol (a GABA A receptor agonist) and baclofen (a GABA B receptor agonist) were injected into freely moving rats. Baclofen produced a dose-related decrease in frequency of RSA in the range 1 to 9 mg/kg i.p. and abolished RSA at 27 mg/kg. Muscimol produced an increase in RSA frequency with an inverted U-shaped dose response curve in the range 0.00001 to 1.0 mg/kg with maximal effect at 0.001 mg/kg. The effects of classical anxiolytic drugs in the present test resemble those of the GABA B receptor agonist baclofen more than they resemble those of the GABA A receptor agonist muscimol but it is possible that they are acting via GABA systems which employ low rather than high affinity GABA A receptors or through some transmitter system other than GABA.

新しい脳循環代謝改善薬１‐（３，４‐Ｄｉｍｅｔｈｏｘｙｐｈｅｎｙｌ）‐２‐（４‐ｄｉｐｈｅｎｙｌｍｅｔｈｙｌｐｉｐｅｒａｚｉｎｙｌ）ｅｔｈａｎｏｌ ｄｉｈｙｄｒｏｃｈｌｏｒｉｄｅ（ＮＣ‐１１００）の中枢薬理作用

The effects of NC-1100 on the central nervous system were analyzed behaviorally and electroencephalographically in mice, rabbits and mongolian gerbils, using ifenprodil as a control material. NC-1100 showed potentiating effects on spontaneous locomotor activities and excitatory motor activities induced by methamphetamine, but did not affect the rotarod test, traction test, sleeping time induced by pentobarbital, analgesic test, anticonvulsant test (MES and pentetrazol test), body temperature and group toxicity induced by methamphetamine. Following i.v. injection of NC-1100 to rabbits with chronically implanted electrodes, electroencephalographic properties in spontaneous EEGs such as fast waves with low voltages in the neocortex became distinguished slightly. Seizure discharges produced by stimulation of the dorsal hippocampus were slightly inhibited, but arousal responses produced by stimulation of the midbrain reticular formation or the posterior hypothalamic area were not inhibited. Furthermore, the effects of NC-1100 on functional recovery after transient cerebral ischemia in gerbils were not distinct. Based on these results, NC-1100 was considered to be an agent that improves cerebral metabolism and selectively increases cerebrovascular blood flow with few central nervous actions.

新規非ベンゾジアゼピン系抗不安薬，ＳＣ‐４８２７４の脳波学的研究

The electroencephalographic (EEG) effects of SC-48274 were investigated in conscious rabbits and compared with those of buspirone and diazepam. SC-48274 (20-30 mg/kg, i.v.) evoked an increase in drowsy EEG pattern period. Diazepam (2-3 mg/kg, i.v.) also increased the drowsy EEG pattern, while buspirone (0.5 mg/kg, i.v.) increased the arousal EEG pattern period. Neither SC-48274 nor buspirone affected the EEG arousal response to both auditory stimulation and electrical stimulation of the midbrain reticular formation of the posterior hypothalamus, while diazepam markedly suppressed the responses to both stimulations. The recruiting response to centromedian thalamic stimulation was not significantly affected by SC-48274 and buspirone, and it was slightly enhanced by diazepam. Neither SC-48274 nor buspirone had any effect on the photic driving response to flash light in the occipital cortex, while the response was markedly suppressed by diazepam. The duration of afterdischarges induced by electrical stimulation of the dorsal hippocampus was slightly inhibited by SC-48274 and markedly inhibited by diazepam, while buspirone enhanced the duration. These results suggest that the EEG effect of SC-48274 is quite different to those of buspirone and diazepam with respect to the qualitative aspects. We also suggest that SC-48274, unlike diazepam, is an effective anxiolytic drug with weak sedation.

Characterization and Modification of Brain Activity with Deep Brain Stimulation in Patients in a Persistent Vegetative State: Pain‐Related Late Positive Component of Cerebral Evoked Potential

A series of eight patients in a persistent vegetative state (PVS) were subjected to chronic deep brain stimulation (DBS) for the purpose of promoting recovery from the PVS. The characteristics of the brain activity in these patients were evaluated from the late positive component of the cerebral evoked potential in response to painful stimuli (pain-related P250). While any neurological scoring system for the comatose state includes evaluations of motor reactions to painful stimuli, the pain-related P250 is unique in terms of its ability to assess the cortical responsiveness to painful stimuli directly and quantitatively without involving functions of the motor system. It was found that the pain-related P250 was more or less depressed in patients in a PVS. It was repeatedly demonstrated in four patients, however, that the pain-related P250 could be transiently increased by preceding stimulation of the mesencephalic reticular formation. Furthermore, a persistent increase in the pain-related P250 was produced in these four patients following chronic DBS of the mesencephalic reticular formation or nonspecific thalamic nuclei for more than 6 months, and this was correlated with the clinical improvements. These results imply that responsiveness at the cortical level to pain is depressed in the PVS. It also appears that some fraction of the depression may, however, be functionally produced and potentially reversible.

Electroencephalographic study with rolipram (ME 3167), a selective inhibitor of adenosine 3',5'-monophosphate phosphodiesterase, in rabbits

The electroencephalographic (EEG) effects of rolipram were investigated in rabbits with chronic electrode implants. Intravenous administration of rolipram at 10 to 100 micrograms/kg evoked an increase in the arousal EEG pattern period (low amplitude fast waves) in the cortical EEG and synchronization of the hippocampal theta waves with increased voltages. Rolipram at higher doses caused behavioral excitation in rabbits. Rolipram did not affect EEG arousal responses to both auditory stimulation (2000 Hz, monotone) and electrical stimulation (100 Hz, 0.1 msec, 3-6 V) of the midbrain reticular formation or the posterior hypothalamus. The recruiting response induced by centromedian thalamic stimulation at a low frequency (7 Hz, 0.1 msec, 4-8 V) was not altered by rolipram. Rolipram was without effect on the photic driving response to flash light (2 Hz) in the occipital cortex. Rolipram caused a slight increase in the duration of after discharges induced by electrical stimulation (50 Hz, 0.5 msec, 4-20 V) of the dorsal hippocampus. These results suggest that rolipram is a drug that causes the EEG arousal pattern.

Muscle tone suppression and stepping produced by stimulation of midbrain and rostral pontine reticular formation

Stimulation of the midbrain retrorubral (RRN), ventral paralemniscal tegmental field (vFTP), reticular tegmental (TRN), and pedunculopontine tegmental (PPN) nuclei was found to produce bilateral suppression of muscle tone in the unanesthetized, decerebrate animal. The RRN is the most rostral area shown to produce such suppression. This muscle tone suppression was frequency- and intensity-dependent. At low stimulus intensities, bilateral suppression was produced at these sites. At higher current and frequency levels, 2 types of muscle responses were found, excitation in PPN and RRN and initial suppression followed by excitation in TRN and vFTP. The mean latency to muscle tone suppression was not significantly different in TRN (36.8 msec) and RRN (36.5 msec). However, muscle tone suppression latency was significantly shorter in vFTP (31 msec) and PPN (27.1 msec). In addition to muscle tone suppression, stepping-like activity could be elicited at the same points by consecutive train stimulations in PPN and single train stimulation in TRN and vFTP. Thus, systems producing atonia are colocalized with those producing locomotion. We hypothesize that the midbrain atonia regions control more caudal regions producing muscle tone suppression in REM sleep, and that the locomotor and atonia eliciting regions are normally coactivated during REM sleep.

Partial involvement of monoamines and opiates in the inhibition of rat spinal nociceptive neurons evoked by stimulation in midbrain periaqueductal gray or lateral reticular formation

In rats anesthetized with sodium pentobarbital, we tested the effects of systemic or intrathecal administration of the opiate antagonist naloxone, the serotonergic antagonist methysergide, or the adrenergic antagonist phentolamine, on inhibition produced by electrical stimulation in midbrain periaqueductal gray (PAG) or lateral reticular formation (LRF) of the responses of single lumbar dorsal horn neurons to noxious heating (50–54 °C, 10 s) of hindpaw skin. Systemically administered naloxone (1–10 mg/kg i.v.) reduced (20% below predrug inhibition) inhibition from PAG and/or LRF in5/12 units and had no effect in the remainder. Systemic methysergide (2–6 mg/kg i.v.) selectively reduced PAG-evoked inhibition in 6 units, while inhibitions from both PAG and LRF stimulation were reduced in one unit and unaffected in 8 units. Systemic phentolamine (2–4 mg/kg) reduced LRF-evoked inhibition in 4 units, while inhibitions from PAG and LRF were reduced in one unit and unaffected in 5. Intrathecally applied methysergide reduced or abolished PAG-evoked inhibition in8/16 units and reduced or abolished LRF-evoked inhibition in6/14 units. Reductions in the level of inhibition were reversible in one-half of the cases, whereas they persisted for over 2 h in the remainder. The mixed effects of both systemically and intrahecally administered drugs suggest that monoamines and opiates may be partly involved in spinal inhibitory mechanisms activated from the midbrain.

Identification of two types of excitatory monosynaptic inputs in frog spinal motoneurones

Synaptic responses induced in motoneurones by stimulation of dorsal root (DR) and reticular formation (RF) were recorded intracellularly in the isolated frog spinal cord. Argiopine (spider neurotoxin, a selective blocker of glutamate receptors of the non-N-methyl-D-aspartate (non-NMDA) type) in concentrations from 3 x 10(-7) to 1 x 10(-5) M effectively inhibited di- and polysynaptic components of excitatory postsynaptic potentials (EPSPs) induced by DR and RF stimulation. The monosynaptic component of the RF response was inhibited by argiopine, whereas the monosynaptic component of DR response was actually enhanced. All types of EPSPs studied were blocked by kynurenate (1-2 x 10(-3) M). D,L-2-Amino-5-phosphonovaleric acid (1 x 10(-4) M) slightly diminished the amplitude only of polysynaptic DR responses. A special type of argiopine-resistant, non-NMDA glutamate receptor is assumed to be involved in the generation of an EPSP by the monosynaptic DR input.

新規非ベンゾジアゼピン系抗不安薬，Ｂｕｓｐｉｒｏｎｅおよびその代謝物１‐（２‐Ｐｙｒｉｍｉｄｉｎｙｌ）ｐｉｐｅｒａｚｉｎｅ（１‐ＰＰ）の脳波学的研究

The electroencephalographic (EEG) effects of buspirone and its major metabolite, 1-(2-pyrimidinyl)piperazine (1-PP), were investigated in rabbits with chronic electrode implants, and the effects were compared with those of diazepam. Intravenous administration of buspirone at 0.1 to 1.0 mg/kg evoked an increase in the arousal EEG pattern period (low amplitude fast waves) in the cortical EEG and synchronization of the hippocampal theta waves with decreased voltages, whereas both 1-PP (0.5 to 2.0 mg/kg, i.v.) and diazepam (1.0 and 2.0 mg/kg) evoked an increase in the drowsy EEG pattern periods: high voltage slow waves and spindle bursts in the cortical EEG and desynchronization of the hippocampal theta waves. Buspirone at higher doses caused behavioral excitation in rabbits, whereas both 1-PP and diazepam produced sedation. Buspirone did not affect EEG arousal responses to both auditory stimulation (2,000 Hz, monotone) and electrical stimulation (100 Hz, 0.1 msec, 3-6 V) of the midbrain reticular formation or the posterior hypothalamus. However, 1-PP tended to inhibit the EEG arousal response to auditory stimulation but not brain stimulation, and diazepam markedly suppressed the responses induced by both stimulations. The recruiting response induced by centromedian thalamic stimulation at a low frequency (7 Hz, 0.1 msec, 4-8 V) was not affected by buspirone, 1-PP and diazepam. Neither buspirone nor 1-PP had an effect on the photic driving response to a flash light (2 Hz) in the occipital cortex of the rabbit, whereas the response was suppressed by diazepam. Both buspirone and 1-PP enhanced the duration of after discharges induced by electrical stimulation (50 Hz, 0.5 msec, 4-15 V) of the dorsal hippocampus, whereas diazepam markedly inhibited the afterdischarges. These results suggest that the EEG effect of buspirone is quite different to those of 1-PP and diazepam in qualitative aspects. It is also suggested that buspirone, unlike diazepam, is an effective anxiolytic drug without a sedative effect.

Plasma epinephrine modulates the cerebrovasodilation evoked by electrical stimulation of dorsal medulla

We examined whether plasma epinephrine contributes to the increase in regional cerebral blood flow (rCBF) evoked by electrical stimulation of the dorsal medullary reticular formation (DMRF). Rats were anesthetized (α-chloralose, 30 mg/kg, s.c.), paralyzed and artificially ventilated. The DMRF was electrically stimulated through microelectrodes stereotaxically implanted. During stimulation, blood gases and arterial pressure were monitored and maintained within normal range. rCBF was determined in 11 dissected brain regions using the [ 14C]iodoantipyrine technique. Plasma epinephrine and norepinephrine were measured radionzymatically in rats with intact adrenals or adrenalectomy, and with or without infusion of epinephrine. DMRF stimulation induced widespread increases in rCBF associated with a 50-fold increase in plasma epinephrine and a 20-fold increase in norepinephrine without changes in the electroencephalogram. In contrast, stimulation of the adjacent medial longitudinal fasciculus had no effect upon rCBF or plasma catecholamines. Acute bilateral adrenalectomy produced regionally selective reductions in the stimulation-coupled increases in rCBF throughout brain ( P < 0.05). Infusion of epinephrine in adrenalectomized rats to levels comparable to those observed in intact animals during DMRF stimulation did not by itself modify rCBF. However, when infused in conjunction with stimulation of the DMRF, but not medial longitudinal fasciculus, epinephrine fully restored the stimulus-related increases in rCBF in all brain regions to levels comparable to those observed in intact rats. We conclude that stimulation of the DMRF elevates rCBF through two mechanisms: by a neurally-mediated increase in local metabolism and thereby flow (adrenal independent secondary vasodilation) and by releasing epinephrine from adrenal medulla which secondarily acts to increase rCBF by an action on brain.

Inhibition by 8-hydroxy-2-(di-n-propylamino) tetralin and SM-3997, a novel anxiolytic drug, of the hippocampal rhythmical slow activity mediated by 5-hydroxytryptamine1A receptors

Electrophysiological studies using spectral analysis techniques were undertaken in rabbits to determine whether or not hippocampal rhythmical slow activity (RSA, theta wave activity) was affected by the 5-hydroxy-tryptamine1A (5-HT1A) agonists 8-hydroxy-2-(di-n-propyl-amino) tetralin (8-OH-DPAT) and 3a alpha, 4 beta, 7 beta, 7a alpha-hexahydro-2-(4-(4-(2-pyrimidinyl)-1-piperazinyl)-butyl)-4, 7-methano-1H-isoindole-1,3(2H)-dione dihydrogen citrate (SM-3997, a newly synthesized anxiolytic drug). Intravenous administration of 8-OH-DPAT and SM-3997 induced a desynchronized pattern with low-amplitude slow wave activity in the hippocampal EEG and inhibited RSA generation following stimulation of the midbrain reticular formation. RSA was also inhibited by 5-HT1A related anxiolytics such as buspirone, gepirone, and ipsapirone. The effects of 8-OH-DPAT and SM-3997 on the hippocampal RSA were blocked by pindolol, which has 5-HT1A antagonistic activity. Direct microinjection of these 5-HT1A selective agonists into the hippocampus inhibited generation of the hippocampal RSA. These findings indicated that 8-OH-DPAT and SM-3997 inhibited the hippocampal RSA by acting on hippocampal 5-HT1A receptors.

Electrical stimulation of brainstem nuclei: Elicitation, modification, and conditioning of the rabbit nictitating membrane response.

Electrical stimulation of the reticular formation, pars oralis of the spinal trigeminal, abducens, and accessory abducens nuclei was used to assess the role of these sites in the elicitation, reflex modification, and classical conditioning of the rabbit's nictitating membrane response (NMR). Although electrical brain stimulation of the targeted sites revealed comparable levels of unconditioned responses, the spinal trigeminal nucleus was the only site at which reflex modification and conditioned response acquisition occurred reliably. These findings suggest that a locus of conditioned stimulus and unconditioned stimulus interaction, mediating either or both reflex modification and NMR conditioning, is on the sensory side of the reflex arc, at the pars oralis of the spinal trigeminal nucleus.

Intracellular analysis of trigeminal motoneuron rhythmical activity during stimulation of pontomedullary reticular formation in anesthetized guinea pig.

1. The effects of repetitive stimulation of the nucleus pontis caudalis and nucleus gigantocellularis (PnC-Gi) of the reticular formation on jaw opener and closer motoneurons were examined. The PnC-Gi was stimulated at 75 Hz at current intensities less than 90 microA. 2. Rhythmically occurring, long-duration, depolarizing membrane potentials in jaw opener motoneurons [excitatory masticatory drive potential (E-MDP)] and long-duration hyperpolarizing membrane potentials [inhibitory masticatory drive potentials (I-MDP)] in jaw closer motoneurons were evoked by 40-Hz repetitive masticatory cortex stimulation. These potentials were completely suppressed by PnC-Gi stimulation. PnC-Gi stimulation also suppressed the short-duration, stimulus-locked depolarizations [excitatory postsynaptic potentials (EPSPs)] in jaw opener motoneurons and short-duration, stimulus-locked hyperpolarizations [inhibitory postsynaptic potentials (IPSPs)] in jaw closer motoneurons, evoked by the same repetitive cortical stimulation. 3. Short pulse train (3 pulses; 500 Hz) stimulation of the masticatory area of the cortex in the absence of rhythmical jaw movements activated the short-latency paucisynaptic corticotrigeminal pathways and evoked short-duration EPSPs and IPSPs in jaw opener and closer motoneurons, respectively. The same PnC-Gi stimulation that completely suppressed rhythmical MDPs, and stimulus-locked PSPs evoked by repetitive stimulation to the masticatory area of the cortex, produced an average reduction in PSP amplitude of 22 and 17% in jaw closer and opener motoneurons, respectively. 4. PnC-Gi stimulation produced minimal effects on the amplitude of the antidromic digastric field potential or on the intracellularly recorded antidromic digastric action potential. Moreover, PnC-Gi stimulation had little effect on jaw opener or jaw closer motoneuron membrane resting potentials in the absence of rhythmical jaw movements (RJMs). PnC-Gi stimulation produced variable effects on conductance pulses elicited in jaw opener and closer motoneurons in the absence of RJMs. 5. These results indicate that the powerful suppression of cortically evoked MDPs in opener and closer motoneurons during PnC-Gi stimulation is most likely not a result of postsynaptic inhibition of trigeminal motoneurons. It is proposed that this suppression is a result of suppression of activity in neurons responsible for masticatory rhythm generation.

Functional integration of the rat hippocampal tissue, transplanted into the rabbit septum

Embryonal tissue of the rat hippocampus (E17–18) was grafted into small acute cavity within the dorsal septum of adult rabbit after interruption of septo-hippocampal connections. Histological analysis (Nissl stain), performed 6–8 weeks later, revealed surviving hippocampal grafts in 14 out of 29 grafted animals (48%). Some of the grafts were displaced into the ventricle and had only minor contact with the host septum; some others, residing in the septum, were separated from the host tissue by continuous glial scar. Six grafts (33%) were morphologically well integrated with the host septum. The grafts contained mature pyramidal neurons but their organization into layer was absent. No signs of rejection were observed in the grafts, which were not subjected to microelectrode investigation in chronic conditions. The grafts, which for 5–9 successive days were penetrated by microelectrodes, were heavily infiltrated by lymphocytes and had necrotic areas. Electrophysiological testing revealed the absence of spontaneous neuronal activity, or the presence of hypersynchronous epileptiform bursts in isolated grafts. The 4 integrated grafts, investigated electrophysiologically, contained neurons with normal spontaneous activity of two types: low-frequency discharges with complex spikes and high-frequency single spikes, sometimes with short periods of weak rhythmic modulation in the θ-range. Characteristics of spontaneous activity of the xenografted hippocampus are very close to those described in the rat hippocampus in situ. Rhythmic θ-modulation of neuronal activity appeared or increased in stability after physostigmine injection to the host, after electrical stimulation of the host's midbrain reticular formation and ventral part of diagonal band, and after multimodal sensory stimulation of the host. The frequency of θ-bursts in the grafts was identical to that of neurons of the host septum (4.5–6.5 Hz). Besides the θ-modulation sensory stimuli evoked tonic suppression or activation of discharges, phasic reactions and on-effects. Electrical stimulation of lateral septum and diagonal band evoked orthodromic and antidromic discharges of the grafted cells. Normal spontaneous and evoked activity of the grafted cells deteriorated after 5–11 successive days of microelectrode investigation. It is concluded that xenografts of nervous tissue, developing without immunosuppression, have a low rate of survival and are vulnerable to immune response after mechanical interruption of integrity of the blood-brain barrier. Nevertheless their normal activity and close functional integration with the host brain, apparently depending on development of chimeric synapses, is possible.