Brainstem influences on transmission of somatosensory information in the spinocervicothalamic pathway

The inhibition of somatosensory responses of lateral cervical nucleus neurons resulting from stimulation of the brainstem has been investigated. Single unit extracellular recordings were obtained from neurons in the lateral cervical nucleus of chloralose-anesthetized cats. Electrical stimulation of the periaqueductal gray, nucleus raphe magnus, nucleus cuneiformis, and nuclei reticularis gigantocellularis and magnocellularis was found to be very effective in inhibiting the responses of lateral cervical nucleus neurons evoked by electrical or tactile stimulation of the skin. Additional experiments were performed to determine whether the inhibitory effects were mediated in the spinal cord dorsal horn or in the lateral cervical nucleus. These experiments which examined the effect of brainstem stimulation on the responses induced by stimulation of the dorsolateral funiculus or on the antidromic latency of activation of lateral cervical nucleus neurons from thalamus, revealed that most and possibly all the inhibition could be accounted for by an action on the spinal cord. These results are consistent with other studies showing that spinocervical tract cells in the spinal cord can be inhibited by stimulation of the same brainstem regions.     

Nucleus accumbens to globus pallidus GABA projection: Electrophysiological and iontophoretic investigations

Extracellular recordings were obtained from neurons in the nucleus accumbens and globus pallidus of urethane anesthetized rats. Eight neurons in the nucleus accumbens were activated antidromically following stimulation of the globus pallidus. Calculated conduction velocities were 0.4–1.5 m/sec, indicative of small unmyelinated fibers.A total of 74 of 153 neurons in the globus pallidus responded to stimulation of the nucleus accumbens. Of these neurons 4 (2.7%) were excited only, 46 (30.1%) were inhibited only and 24 (15.7%) had sequential effects of excitation and inhibition. Iontophoretic application of picrotoxin was found to attenuate or abolish the poststimulus inhibition in one-half of the neurons examined. The 74 neurons which responded to stimulation of the nucleus accumbens had slower firing frequencies and generally more random firing patterns than neurons which did not respond to stimulation. Fifty-three per cent of all globus pallidus neurons examined had increased spontaneous firing frequencies following the iontophoretic administration of picrotoxin alone. This is indicative of the removal of a tonic GABA input onto these neurons. Most neurons examined had decreased spontaneous firing frequencies following the iontophoretic application of GABA which could be blocked by the iontophoretic application of picrotoxin.The results from antidromic activation, slow conduction velocity, sensitivity to GABA and picrotoxin, and picrotoxin attenuation of the poststimulus inhibitory effect provide evidence of a direct GABAergic projection from the nucleus accumbens to the globus pallidus in the rat.     

Serotonin-mediated inhibition from dorsal raphe nucleus of neurons in dorsal lateral geniculate and thalamic reticular nuclei

Electrophysiological studies using rats anesthetized with chloral hydrate were performed to determine whether or not serotonin originating in the dorsal raphe nucleus (DR) acts as an inhibitory transmitter or neuromodulator on neurons of the dorsal lateral geniculate nucleus (LGN) and neurons located in the thalamic reticular nucleus (TRN) immediately rostral to the dorsal LGN. In the LGN, conditioning stimuli applied to the DR preceding test stimulus to the optic tract and visual cortex inhibited orthodromic and antidromic spikes in about one-third of the relay neurons and in more than half of the intrageniculate interneurons. Conditioning stimulation of the DR also produced an inhibition of the spikes elicited by stimulation of the optic tract and visual cortex of at least three-quarters of the TRN neurons. Iontophoretic application of serotonin (25 nA) inhibited the orthodromic spikes of the LGN relay neuron and TRN neuron. A close correlation was observed between the effects of DR conditioning stimulation and iontophoretic serotonin in the same neurons. The inhibition with DR conditioning stimulation and iontophoretically applied serotonin was antagonized during iontophoretic application of methysergide (15-40 nA), a serotonin antagonist. These results strongly suggest that serotonin derived from the DR acts on the LGN and TRN neurons as an inhibitory transmitter or neuromodulator to inhibit transmission in these nuclei.     

Inhibition of lateral vestibular nucleus neurons by 5-hydroxytryptamine derived from the dorsal raphe nucleus

Electrophysiological studies were performed to elucidate the effect of 5-hydroxytryptamine (5-HT) originating in the dorsal raphe nucleus (DR) on neuronal activity in the lateral vestibular nucleus (LVN) neurons, using cats anesthetized with alpha-chloralose. LVN neurons were classified into monosynaptic and polysynaptic neurons according to their responses to vestibular nerve stimulation. Conditioning stimuli applied to the DR inhibited orthodromic spikes elicited by vestibular nerve stimulation predominantly in polysynaptic neurons of the LVN. The iontophoretic application of 5-HT also inhibited orthodromic spikes of the LVN neurons. A close correlation was observed between the effects of DR conditioning stimulation and iontophoretically applied 5-HT in the same neurons. These inhibitions with both treatments were antagonized during the application of methysergide, a 5-HT antagonist. In the majority of LVN polysynaptic neurons that responded to antidromic stimulation of the ipsilateral or contralateral abducens nucleus, orthodromic spikes elicited by vestibular nerve stimulation were inhibited by DR conditioning stimulation and the iontophoretic application of 5-HT. In contrast, LVN neurons that responded to antidromic stimulation of the vestibulospinal tract were rarely affected by these treatments. These results indicate that 5-HT derived from the DR inhibits the synaptic transmission of LVN polysynaptic neurons ascending to the abducens nucleus, and suggest that 5-HT derived from the DR is involved in the regulation of the vestibulo-ocular reflex.     

An electrophysiological study of convergence of entopeduncular and lateral preoptic inputs on lateral habenular neurons projecting to the midbrain

Extracellular recordings were made from single neurons in the lateral habenular nucleus of urethane-anesthetized rats. Single pulse stimulation of the entopeduncular nucleus influenced the spontaneous activity of 200 out of 293 (68%) lateral habenular neurons tested, with the most frequent response being suppression of activity and initial activation followed by suppression. Single pulse stimulation of the lateral preoptic area influenced the activity of 140 out of 165 (85%) lateral habenular neurons tested. Response were similar to those for entopeduncular stimulation. In a series of 137 lateral habenular units, 85 (62%) were influenced by stimulation of both sites indicating convergence of inputs from these two forebrain areas. Approximately half of the lateral habenular neurons which received converging inputs from entopeduncular nucleus and lateral preoptic area were activated antidromically by stimulation of the fasciculus retroflexus, indicating that they were output neurons. These electrophysiological findings support the suggestion from recent neuroanatomical studies that the lateral habenular nucleus is a site of integration for entopeduncular and limbic inputs and in turn sends signals to the midbrain.     

Caudate unit activity and somal diameters in intact and nigral lesioned cats

In a search for morphofunctional relationships in the head of the caudate nucleus (CN), we recorded extracellular unit activity in intact cats and in cats that had received bilateral injections of 6-OHDA into the substantia nigra (SN) 30 days previously. Only units firing spontaneously and continuously for 2 min were studied. In dorsal regions, potentials were small and iterative at almost constant intervals; the somal diameters were relatively small. In the ventrolateral region, potentials were bigger and appeared in bursts; somal diameters were significantly larger (p less than 0.05). For the centromedial region a histogram of numbers of neurons as a function of diameters revealed a Gaussian distribution extending from small to large neurons. Most dorsal neurons increased their firing rate to radial nerve, visual, SN, and/or nucleus centralis medialis (NCM) stimulation. Ventral neurons usually responded with excitation followed by long lasting inhibition, particularly to SN and NCM stimulation. A few neurons responded to all four inputs and some showed long-lasting potentiation in response to low frequency stimulation, suggesting a more general function. Greatest convergence (65%) was found for NCM and SN inputs. In lesioned cats, there was no SN driving, NCM's inhibitory actions almost disappeared, and the excitatory action of the other stimuli was reduced.     

Location and axonal projection of one type of swallowing interneurons in cat medulla

Extracellular recordings were made from a type of relay neurons of the superior laryngeal nerve (SLN) afferents in the vicinity of the retrofacial nucleus (RFN) in either pentobarbitone-anesthetized or unanesthetized and decerebrate cats, which were paralyzed and artificially ventilated. A total of 26 neurons that could be activated both orthodromically by electrical stimulation of the SLN and antidromically by stimulation of the brainstem were analyzed. All 26 neurons were activated from the ipsilateral SLN and 13 were activated from the contralateral SLN with mean latencies of 7.7 ms and 11.4 ms, respectively. The majority of these neurons were located in the parvocellular reticular formation dorsomedial to the RFN and to the rostral part of the nucleus ambiguus (AMB). Antidromic stimulation of the medulla showed that 22 of the 26 neurons projected to the hypoglossal nucleus (HYP) and 19 neurons tested projected to the AMB. Of these, 15 neurons projected to both the HYP and AMB and two projected to the lateral reticular nucleus as well. Seventeen neurons were tested for their behavior during fictive swallowing which was elicited by continual electrical stimulation of the SLN and monitored by the activity of the hypoglossal nerve. Twelve neurons showed brief (100–200 ms) burst firing at the onset of swallowing; the firing of the other 5 neurons were suppressed during swallowing. Both the swallowing-active and swallowing-inactive neurons projected to the HYP and AMB. Thus, the SLN relay neurons in the vicinity of the RFN might participate in the early stage of SLN-induced swallowing by integrating inputs from SLN afferents.     

Pyramidal influences on ventral thalamic nuclei in the cat

In pericruciate cortex-ablated 'pyramidal cats', discharge changes in single neurons of ventral thalamic nuclei were studied, following stimulation of ipsilateral medullary (MPT) and contralateral cervical (CPT) pyramidal tract. It was seen that cells in ventrolateral nucleus, ventroanterior nucleus and ventromedial nucleus were not significantly (2.2%) modified by impulses coming from MPT and CPT. Conversely, a very high percentage (58.8%) of cells in ventrobasal complex (VB) responded to MPT stimulation (64.4% in ventroposterolateral nucleus, VPL, and 40.7% in ventroposteromedial nucleus, VPM). A considerable number (34.8%) of VPL cells responsive to MPT, were influenced by CPT, while none of the cells in VPM were. The most frequent effect observed in VB neurons, on MPT and CPT stimulation, was excitation followed by depression of discharge.     

Response of nucleus accumbens neurons to amygdala stimulation and its modification by dopamine

Extracellular single unit recordings were obtained from the nucleus accumbens of urethane anesthetized rats. It was found that electrical stimulation of the basal lateral and basal medial nuclei of the amygdala produced strong excitatory responses in neurons of the nucleus accumbens, in particular the medial region. Latencies of activation were relatively short with a mean of 10.7 ms.Dopamine applied iontophoretically had a marked attenuating effect on the excitatory response of nucleus accumbens neurons to amygdala stimulation. The spontaneous activity of all neurons recorded from the nucleus accumbens was also suppressed by dopamine, but the excitatory response was more sensitive to dopamine inhibition than the spontaneous activity.Neurons in the nucleus accumbens showed a variety of responses to single-pulse electrical stimulation of the ventral tegmental area (VTA). Some units in the nucleus accumbens received convergent inputs from both the amygdala and the VTA. Stimulation of the VTA also attenuated the response of nucleus accumbens neurons to excitatory inputs from the amygdala. A train of 10 pulses (0.15 ms, 200–600 αA) at 10 Hz delivered to the VTA at 100 ms before stimulation of the amygdala caused attenuation of the original excitatory response. The attenuating effect could be observed irrespective of whether individual single-pulse stimulation of the VTA elicited a response in that particular accumbens neuron or not. 6-Hydroxydopamine injected into the VTA 2 days prior to the recording experiment, or haloperidol injected intraperitoneally 1 h before the recording session, abolished this attenuating effect. However, responses to single-pulse stimulations of the VTA were not abolished. The results suggest that the attenuation of the excitatory response to amygdala stimulation was due to the release of dopamine from mesolimbic dopaminergic neurons. Responses to single-pulse stimulations of the VTA were probably due to activation of non-dopaminergic neurons projecting from the same area.It is suggested as a working hypothesis that this inhibitory effect of dopamine may be an important function of the mesolimbic dopamine pathway in modulating the extent to which limbic structures can exert an influence on the motor system through the accumbens.     

Oxytocin neurons in the supraoptic nucleus receive excitatory inputs from the bilateral dorsomedial hypothalamic nuclei

To examine whether inputs from the dorsomedial hypothalamic nucleus (DMH) alter the discharge of putative oxytocin (OT) neurons with hypothesis that excitation of DMH neurons would increase the activity of OT neurons, electrical stimulation was applied to the DMH in both sides of the hypothalamus while electrical activity of single OT neurons in the supraoptic nucleus (SON) was recorded in urethane-anesthetized lactating rats. About half of the OT neurons showed orthodromic excitation or inhibition followed by excitation in response to electrical stimulation of the DMH on both sides. Continuous electrical stimulation of the DMH both ipsi- and contralateral to the recording side at 10-50 Hz for 30-60 s increased firing rate in 58% of OT neurons tested. Continuous electrical stimulation of the DMH not only excited spiking activity of single OT neurons but also increased intramammary pressure. The results may suggest that some of the projections from the DMH to the SON are bilateral and possibly contribute to coordinated bilateral activation of OT neurons in the hypothalamus during the milk-ejection reflex.     

Connections of neurons in the region of the nucleus tractus solitarius with the hypothalamic paraventricular nucleus: Their possible involvement in neural control of the cardiovascular system in rats

Extracellular recordings were made from 607 spontaneously firing neurons within the nucleus tractus solitarius (NTS) and its vicinity in urethane-anesthetized male rats. Following electrical stimulation of the hypothalamic paraventricular nucleus (PVN) area, 21% of the neurons were orthodromically excited, 6% were inhibited and 2.5% were antidromically activated. The antidromic spike latencies were 22-64 ms. Among those orthodromically responding neurons, 81 neurons were tested by pressure pulse stimulation of the isolated carotid sinus. The pressure stimulation produced excitation in 7 and inhibition in 13 neurons. Of the 8 tested neurons which were antidromically activated, one neuron was excited and another neuron inhibited by the pressure pulse stimulation. These results provide electrophysiological evidence for reciprocal connections between neurons in the NTS region and the PVN, and give support to the hypothesis that the PVN is involved in the neural control of the cardiovascular system.     

5-羟色胺_7 受体介导刺激中缝背核对视交叉上核光敏神经元单位放电的抑制效应

观察刺激中缝背核（ＤＲ）对大鼠视交叉上核（ＳＣＮ）光敏神经元单位放电的影响，并进行药理学分析。结果表明：刺激ＤＲ能明显抑制ＳＣＮ神经元光诱发放电。这种抑制作用能被５ＨＴ２／７受体拮抗剂ｒｉｔａｎｓｅｒｉｎ 阻断，但不能被选择性５ＨＴ２ 受体拮抗剂１ＮＰ阻断。对５ＨＴ７ 有较高亲和力的神经阻断剂ｃｌｏｚａｐｉｎｅ也能阻断刺激ＤＲ的抑制效应。实验结果提示，刺激ＤＲ对ＳＣＮ 光敏神经元放电的抑制，可能是通过５ＨＴ７ 样受体起作用的     

Enhancement of stimulation-induced ERK activation in the spinal dorsal horn and gracile nucleus neurons in rats with peripheral nerve injury

It has been suggested that low-threshold sensory pathways have an important role in the formation and maintenance of sensory abnormalities which are observed after peripheral nerve injury. In the present study, we examined the involvement of these pathways in the development of hyperexcitability after sciatic nerve injury (SNI) by detecting the intracellular signal molecule. The rats that received a transection of the sciatic nerve 7 days before were electrically stimulated at 0.1 mA and 3 mA in the proximal region of the nerve injury site. We found a small number of phosphorylated extracellular signal-regulated kinase (pERK)-labelled neurons in laminae I-II and III-IV of the spinal dorsal horn in the control rats after 0.1 mA stimulation. By contrast, there was a marked increased of pERK-labelled neurons both in the superficial laminae and laminae III-IV after the same stimulation in the SNI rats. Enhancement of ERK activation induced by 3 mA stimulation was also observed. Immunoreactivity of pERK in gracile nucleus neurons was also dramatically increased after 0.1 mA stimulation to the injured nerve. These data suggest that the rats with peripheral nerve injury had an increased responsiveness to the low- or high-threshold peripheral stimuli in I-II, III-IV and gracile nucleus neurons. Furthermore, SNI rats that received neonatal capsaicin treatment showed a decreased number of pERK neurons after 0.1 mA stimulation in the dorsal horn and gracile nucleus neurons compared to the control rats. Thus, C-fibres may contribute to the enhanced excitability of the low-threshold sensory neurons after peripheral nerve injury.     

Connections of the mesencephalic locomotor region (MLR) III. Intracellular recordings

The responses of neurons in the area of the cat mesencephalic locomotor region (MLR) following stimulation of the entopeduncular nucleus (EN) were recorded intracellularly. At the end of each experiment a precollicular-postmamillary brainstem transection was performed and stimulation of the recording site(s) was employed to induce locomotion on a treadmill. This procedure was assumed to establish that intracellularly studied cells in the vicinity of a locomotion-inducing site were MLR neurons. About 10% of MLR neurons were found to respond to stimulation of the EN at short latencies. Stimulation of MLR efferent pathways was used to identify output neurons by antidromic activation. Very few MLR output neurons were found to receive EN projections (i.e. to respond at short latency following EN stimulation). These experiments support previous results describing a sparse projection from the EN to the MLR. This projection appears to be functionally varied (EPSP, IPSP and EPSP-IPSP responses were observed in MLR neurons following EN stimulation) and to exert its major influence on interneurons, not on output neurons, of the MLR.     

An electrophysiological study of the forebrain projection of nucleus commissuralis: Preliminary identification of presumed A2 catecholaminergic neurons

Using a double-labeling technique (HRP combined with catecholamine fluorescence), up to 80% of all CA-containing neurons visualized in the nucleus commissuralis were found to project to or through the median forebrain bundle area (MFB). In addition at least 90% of all nucleus commissuralis neurons projecting through the MFB were found to be catecholaminergic. In a series of chloral hydrate-anesthetized rats, nucleus commissuralis neurons projecting through the MFB were identified with single-unit recordings by antidromic (AD) activation. These cells had a conduction velocity of about 0.5 m/s and a firing rate of 0-14 spikes/s. The pattern of discharge of these neurons was not correlated with the heart rate; they were unaffected by single-unit stimulation applied to the sciatic nerve but were powerfully excited by vagus nerve stimulation. For comparative purposes, NE-containing neurons were also recorded in the locus coeruleus (A6) in the course of the same experiments; in contrast with MFB-activated commissuralis neurons, A6 neurons were excited by both visceral (vagus nerve) and somatic (sciatic nerve) stimulation. The spontaneous firing rate of MFB-activated commissuralis neurons was inhibited by the intravenous administration of a low dose of the centrally acting antihypertensive agent clonidine (ED50: 28 micrograms/kg).     

Activation of ventrolateral medullary neurons projecting to spinal autonomic areas after chemical stimulation of the central nucleus of amygdala: a neuroanatomical study in the rat

Several studies have shown that the central nucleus of amygdala is involved in cardiovascular regulation. The control of this function may be mediated by activation of the ventrolateral medulla neurons that project to preganglionic neurons located in the intermediolateral nucleus of the spinal cord. The aim of the present study was to examine whether stimulation of the central nucleus of amygdala activated ventrolateral medulla neurons projecting to the intermediolateral nucleus. For this purpose, the injection of a retrograde tracer, the cholera toxin b subunit (CTb), into the intermediolateral nucleus of the T2 segment was combined with immunohistochemical detection of Fos protein following chemical stimulation of the central nucleus of amygdala. Results showed that retrogradely labeled neurons were found throughout the ventrolateral medulla. Moreover, chemical stimulation of the central nucleus of amygdala induced: (1) a decrease of arterial blood pressure; (2) an expression of Fos protein mainly in sub-populations of neurons located in the intermediate and caudal parts of the ventrolateral medulla; (3) a significantly higher number of double labeled neurons (CTb-immunoreactive/Fos-immunoreactive) in the rostral part of the ventrolateral medulla than in the other parts of this region. These results show that the central nucleus of amygdala influences the activity of brainstem neurons projecting to the intermediolateral nucleus. Data were discussed in terms of descending amygdalofugal pathways involved in the hypotension.     

Caudal cuneate nucleus projection to the direct thalamic relay to motor cortex in cat: an electrophysiological and anatomical study

The input to the border region between the ventrolateral nucleus (VL) and ventroposterolateral nucleus (VPL) of the thalamus, VL-VPL, was studied in cats using a combined electrophysiological and anatomical technique. Neurons within this border region receive somatic afferent input and project to a region of the motor cortex having similar receptive fields. In this study we asked the question whether neurons in the VL-VPL border receive input from the dorsal column nuclei (DCN). To answer this question we delivered intra-cortical microstimulation (ICMS) to the motor cortex while a second electrode inserted into the VL-VPL border, filled with a 20% solution of HRP dissolved in KCl, was used to record antidromically activated neurons. When an antidromically activated neuron was encountered and the neuron responded to natural peripheral stimulation, HRP was iontophoretically injected through the recording electrode. After a 48–72 h survival time, cats were sacrificed, and the brain tissue processed according to the method of Hardy and Heimer¹⁰. Labeled cell bodies were found in the caudal cuneate nucleus (CCN) in all injected animals. These results suggested that neurons in CCN project to cells in VL-VPL which in turn project to the motor cortex.     

Processing of spatial information by floccular and non-floccular target neurons in the alert cat

In five alert chronically-prepared cats we studied the response to sinusoidal 3-D whole body rotation of well-isolated vestibular nucleus neurons which were tested for monosynaptic input from the vestibular labyrinth, direct projection to the oculomotor nucleus and, in some cases, inhibition from cerebellar flocculus stimulation. Neurons directly inhibited by flocculus stimulation had significantly greater horizontal–vertical semicircular canal signal convergence than did neurons not inhibited by flocculus stimulation.     

Olfactory and visceral projections to the paraventricular nucleus

Electrophysiological studies were performed to determine if neurons of the paraventricular nucleus (PVN) which receive inputs from the stomach via vagal afferents also respond to nucleus of the solitary tract (NTS) and olfactory bulb (OB) stimulation. We found that the NTS, OB stimulation, and gastric distension depress the firing frequency of PVN neurons. The pathway from the NTS to the PVN contains larger fibers than the projection from the PVN to the NTS.     

Serotonin- and substance P-containing projections to the nucleus tractus solitarii of the rat

The objective of the present study was to determine the location of the neurons that give rise to serotonin- and substance P-containing terminals in the nucleus tractus solitarii. This was done by injecting rhodamine-filled latex microspheres into the nucleus tractus solitarii of rats to retrogradely label neuronal cell bodies and by processing sections from the brains of these animals to determine whether the labelled neurons contained serotonin or substance P immunoreactivity. Serotonin-immunoreactive neurons that projected to the nucleus tractus solitarii were found in the nucleus raphe magnus, nucleus raphe obscurus, nucleus raphe pallidus, and in the ventral medulla, lateral to the pyramidal tract. Substance P-immunoreactive neurons that projected to the nucleus tractus solitarii were found in similar areas but were proportionately less numerous in the nucleus raphe magnus and proportionately more numerous in the nucleus raphe pallidus. It is concluded that neurons in the medullary raphe nuclei, some of which presumably utilize serotonin or substance P as a neurotransmitter, could regulate autonomic function via direct projections to the nucleus tractus solitarii.