Noradrenaline-mediated inhibition by locus coeruleus of spinal trigeminal neurons

Inhibitory effects of conditioning stimulation of the locus coeruleus (LC) on the neuron activity in spinal trigeminal nucleus (STN) were investigated in gallamine-immobilized cats. Field potentials of STN and spike potentials of single relay neurons in STN were orthodromically elicited by ipsilateral alveolar nerve stimulation and antidromically by stimulation of contralateral medial lemniscus. Conditioning stimuli were applied to LC and sensory cortex (SC) at various C-T intervals.

In tracking experiments near the LC region, conditioning stimulation of LC itself produced the most pronounced decrease in amplitude of the STN field potentials. Orthodromic spikes of STN single neurons were significantly reduced by conditioning stimulation of LC as well as SC. In reserpine-treated animals, however, conditioning stimulation of LC failed to produce a decrease in the number of orthodromic spikes, while the inhibitory effect of SC conditioning stimulation remained unaffected. Under these circumstances, intravenous L-dopa and intraventricular noradrenaline reproduced an inhibitory effect of LC conditioning stimulation on orthodromic spike generation, while such an effect was not seen with either dopamine or serotonin. Antidromic spike was unaltered by any of these treatments. Histochemically, catecholamine fluorescence in LC was entirely eliminated after reserpine-treatment, but was restored after L-dopa injection. These results strongly suggest that noradrenaline released from the terminals of neurons originating in LC produces an inhibition of transmission in the STN relay neurons.     

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.     

Effects of L-threo-DOPS, an L-noradrenaline precursor, on locus coeruleus-originating neurons in spinal trigeminal nucleus

Electrophysiological studies using reserpinized cats were performed to examine the effects of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) on the noradrenergic pathway from the locus coeruleus (LC) to the spinal trigeminal nucleus (STN). The spike generation of STN relay neurons induced by trigeminal nerve stimulation was not affected by LC conditioning stimulation nor iontophoretic application of L-threo-DOPS. After intraventricular administration of L-threo-DOPS, the inhibition of the spike generation was seen with LC conditioning stimulation and blocked by iontophoretically applied sotalol, suggesting that L-noradrenaline converted from L-threo-DOPS inhibits transmission of STN relay neurons.     

Pyramidal neurons in rat prefrontal cortex show a complex synaptic response to single electrical stimulation of the locus coeruleus region: Evidence for antidromic activation and GABAergic inhibition using in vivo intracellular recording and electron microscopy

Cognition and acquisition of novel motor skills and responses to emotional stimuli are thought to involve complex networking between pyramidal and local GABAergic neurons in the prefrontal cortex. There is increasing evidence for the involvement of cortical norepinephrine (NE) deriving from the nucleus locus coeruleus (LC) in these processes, with possible reciprocal influence via descending projections from the prefrontal cortex to the region of the LC. We used in vivo intracellular recording in rat prefrontal cortex to determine the synaptic responses of individual neurons to single electrical stimulation of the mesencephalic region including the nucleus LC. The most common response consisted of a late-IPSP alone or preceded by an EPSP. The presence of an early-IPSP following the EPSP was sometimes detected. Analysis of the voltage dependence revealed that the late-IPSP and early-IPSP were putative K⁺- and Cl⁻ dependent, respectively. Synaptic events occurred following short delays and were inconsistent with the previously reported time for electrical activation of unmyelinated LC fibers. Moreover, systemic injection of the adrenergic antagonists propranolol (β receptors), or prazosin (α1 receptors), did not block synaptic responses to stimulation of the LC region. Finally, certain neurons were antidromically activated following electrical stimulation of this region of the dorsal pontine tegmentum. Taken together, these results suggest that the complex synaptic events in pyramidal neurons of the prefrontal cortex that are elicited by single electrical stimulation of the LC area are mainly due to antidromic activation of cortical efferents. Further insight into the chemical circuitry underlying these complex synaptic responses was provided by electron microscopic immunocytochemical analysis of the relations between the physiologically characterized neurons and either 1) GABA or 2) dopamine-β-hydroxylase (DBH), a marker for noradrenergic terminals. GABA-immunoreactive terminals formed numerous direct symmetric synapses on somata and dendrites of pyramidal cells recorded and filled with lucifer yellow (LY). In contrast, in single sections, noradrenergic terminals immunoreactive for DBH rarely contacted LY-filled somata and dendrites. These results support the conclusion that IPSPs observed following single electrical stimulation of the LC region are mediated bu GABA, with little involvement of NE. These IPSPs, arising from antidromic invasion of mPFC cells innervating the LC, may improve the signal-to-noise ratio and favor a better responsiveness of neighboring neurons to NE released in the mPFC. © 1996 Wiley-Liss, Inc.     

Dorsal raphe stimulation produces inhibitory effect on trigeminal nucleus neurons.

Inhibitory effects of conditioning stimulation of the dorsal raphe nucleus (DR) on the neuron activity in the rostral part of spinal trigeminal nucleus (STN) were studied in cats for the purpose of comparison with the inhibition induced by locus coeruleus (LC) stimulation. DR conditioning stimulation reduced the orthodromic field potential in STN elicited by inferior alveolar nerve stimulation, and enhanced the antidromic field potential in the trigeminal nerve evoked by STN stimulation; but the inhibitory effects of DR stimulation were considerably weaker than those of LC stimulation. In tracking experiments near the raphe nucleus, conditioning stimulation of DR itself produced the most pronounced decrease in the STN field potential. Orthodromic spike number of STN relay neurons was significantly reduced by DR conditioning stimulation; however, the threshold for the conditioning stimulus to the DR was much higher than that to the LC. Antidromic spike generation of the STN neurons was unaltered by conditioning stimulation of both DR and LC. DR stimulation elicited a field potential in STN, which followed high frequency stimuli up to 200 HZ. A single fiber action potential was also obtained in STN by DR stimulation. STN stimulation produced a field potential in DR, which followed high frequency stimuli. It is suggested from these findings that conditioning stimulation of DR produces a direct inhibition of transmission in STN neurons; however, this stimulation has less effect on these neurons than does stimulation of the LC.     

Evidence of facilitatory coerulospinal action in lumbar motoneurons of cats

Functional connectivity of the feline coerulospinal projection was delineated by utilizing the combined approaches of antidromic activation and electrical stimulation. We isolated 25 locus coeruleus (LC) neurons that were electrophysiologically identified and histologically verified and that could be driven by stimulating the spinal cord. Antidromicity of the spike potentials was confirmed by the constant latency, the high frequency (100 Hz) following, fractionation of the initial segment-somatodendritic potential, and collision between the antidromic and the spontaneous orthodromic spikes. The mean conduction speed was20 ± 8m/sec(range= 7to32m/sec). Intracellular studies revealed facilitatory LC actions in 22 lumbar motoneurons (MNs), In 13 MNs, LC activation alone produced slow-rising excitatory postsynaptic potentials (EPSPs) of3 ± 1mV amplitude that lasted 4–30 msec. Six of the 13 MNs discharged action potentials upon LC stimulation. In the remaining 9 MNs, no observable potential change was registered after LC activation. Antecedent LC stimulation consistently potentiated the synaptic efficacy of testing dorsal root shocks. The enhancement of synaptic activation was antagonized by systemic injection of phenoxybenzamine (3 mg/kg). These results suggest that facilitation of MNs by the LC is at least in part mediated by distal dendritic depolarization. Those MNs that exhibited augmented excitability but no demonstrable EPSPs may have been activated by norepinephrine-mediated synaptic modulation.     

Electrophysiological and biochemical responses of noradrenergic neurons to a non-amphetamine CNS stimulant

Amfonelic acid (AFA), a potent non-amphetamine CNS stimulant, has been shown previously to have marked effects on dopamine (DA) metabolism and DA neuronal activity, but no effect on norepinephrine (NE) metabolism. AFA is known to inhibit the NE neuronal uptake mechanism. Other NE uptake inhibitors, such as desipramine (DMI), have been shown to decrease the firing rate of NE-containing locus coeruleus (LC) neurons. The purpose of the present study was to compare the actions of AFA and DMI electrophysiologically on LC neurons, and biochemically on NE metabolism in whg rate, with DMI being more potent. Brain NE metabolism was not influenced by either AFA or DMI at doses considerably higher than those which were effective in reducing NE neuronal impulse flow. Thus, NE uptake inhibition coupled with a decrease in impulse flow results in no net change in NE metabolite formation. The effects of AFA on LC unit activity do not seem to be due to its marked effects on brain DA, since DA receptor blockade with haloperidol had little effect on LC unit responsiveness to AFA (or amphetamine). Whereas AFA has dramatic effects on DA metabolism via enhanced release per impulse, the drug has minimal effects on NE metabolism, and this specificity of action may be related to differences in NE and DA transmitter storage mechanisms. It is concluded that the effects of AFA on NE neuronal firing rate are likely due to the drug's DMI-like action and not to enhanced NE release per impulse.     

Extracellular characteristics of putative cholinergic neurons in the rat laterodorsal tegmental nucleus

The extracellular electrophysiological properties of neurons in the laterodorsal tegmental nucleus (LDT), a major source of cholinergic afferents to the thalamus, were studied in chloral hydrate-anesthetized rats. A combination of antidromic activation from the thalamus and histological verification of recording sites was used to correlate the identity of extracellular recordings in the rat LDT with cholinergic neurons in that region. All neurons antidromically activated by stimulation of the anteroventral thalamus were histologically verified to be within clusters of cholinergic (NADPH-d-positive) cells in the LDT or in the adjacent nucleus locus coeruleus (LC). The thalamically projecting LDT neurons had a homogeneous neurophysiological profile consisting of long duration action potentials (mean = 2.5 ms), slow conduction velocities (mean = 0.78 m/s), and lengthy chronaxie values (mean = 0.725 ms). The appearance and axonal characteristics of these neurons resembled those of noradrenergic LC neurons, but the two populations exhibited substantially different spontaneous activity patterns and sensory responsiveness. These characteristics may be useful in the preliminary identification of putative cholinergic neurons in vivo, and thereby provide a foundation for exploring the neuropharmacology, afferent modulation, sensory responsiveness and behavioral correlates of the brainstem cholinergic system.     

Tonic activation of locus coeruleus neurons by systemic or intracoerulear microinjection of an irreversible acetylcholinesterase inhibitor: increased discharge rate and induction of C-fos.

Recent studies in this laboratory have demonstrated that intramuscular injection of the irreversible acetylcholinesterase (AChE) inhibitor, soman (pinacolylmethylphosphonofluoridate), produces a rapid (1-2 h) and profound depletion (70% of control) of norepinephrine (NE) in the olfactory bulb and forebrain. NE is decreased only in convulsing animals. As NE-containing locus coeruleus (LC) neurons provide the only NE input to the olfactory bulb and the major NE innervation of the forebrain, the reduction of NE suggests that soman may cause tonic activation of LC neurons leading to rapid depletion of NE. Activation of LC may result from: (i) facilitation of cholinergic transmission in LC; (ii) soman-induced activation of excitatory inputs to LC; or (iii) generalized activation of LC neurons due to seizures. The present experiments were designed to assess these alternatives. We examined whether LC neuronal activity, c-fos expression, and AChE staining are altered after peripheral (systemic) or direct intracoerulear injection of soman in anesthetized rats. Both modes of soman administration rapidly and potently increase the spontaneous discharge rate of LC neurons. This activation was associated with a desynchronization of the electroencephalogram, but not with seizures. The discharge of LC neurons remained elevated at all postsoman intervals examined (up to 2 h) and was rapidly and completely reversed by systemic injection of the muscarinic receptor antagonist scopolamine hydrochloride, but not by the nicotinic receptor antagonist mecamylamine. Both systemic and intracoerulear soman administration completely inhibited AChE staining in LC and rapidly induced the expression of c-fos in LC neurons. These results demonstrate that soman potently and tonically activates LC neurons. This effect appears to be mediated by direct inhibition of AChE in LC leading to a rapid accumulation of ACh. Unhydrolyzed ACh tonically activates LC neurons via muscarinic receptors. Soman-induced activation of LC neurons does not require seizures. We conclude that depletion of forebrain and olfactory bulb NE after systemic administration of soman results from tonic hypercholinergic stimulation of LC.     

Effects of dopamine and norepinephrine on neuronal activity of the olfactory tubercle

The effects of iontophoretic administration of norepinephrine (NE) and dopamine (DA) on olfactory tubercle (OT) neurons that respond to lateral hypothalamus (LH) or locus coeruleus (LC) electrical stimulation were studied. NE and DA decreased the frequency of OT neurons which were increased or decreased by the LH stimulation. An increased firing of OT neurons following NE or DA administration was less frequently observed. NE administration decreased the firing of OT neurons that responded to LC stimulation. These results suggest that the LC fibers which reach the OT use NE as a neurotransmitter. DA administration also suppressed the unitary discharge of OT neurons responding to LC stimulation. The increase in frequency of OT neurons observed following LH stimulation cannot be attributed to DA. The possibility that other suspected neural transmitters are involved in this effect is discussed.     

Excitation and inhibition processes in the neurons of the thalamic motor nuclei of normal cats and following an N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced lesion of the nigrostriatal dopaminergic system

Peculiarities of excitation and inhibition evoked in motor thalamic nuclei (VA-VL) neurons by electrical stimulation of red nucleus were studied on intact cats and after injection of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 5 mg/kg i.m., p.d. during five days). Two days after the last injection as much as 48% of nigral neurons were destroyed and the content of dopamine in the caudate nucleus fell to 30% as compared to intact animals. Before acute experiments all cats were anaesthetized with ketalar and immobilized with myorelaxine. It was found that MPTP injections caused a decrease of the inhibition duration and effectiveness in relay and nonrelay VA-VL neurons. The inhibition deficiency was accompanied by shortening of latencies of orthodromic responses evoked by red nucleus stimulation and facilitation of antidromic spikes invasion into somata of relay neurons after motor cortex stimulation. It was suggested that the reduction of GABAergic nigro-thalamic influences modulated by dopamine underlay the developing deficiency of inhibition.     

Olfactory tubercle's different neural elements activated by locus coeruleus

Olfactory tubercle (OT) evoked potentials were recorded following single pulse stimulation of the locus coeruleus (LC) in cats. Also, OT unit responses were recorded extracellularly following LC repetitive stimulation in rats. In order to characterize the properties of OT evoked potentials, these responses were evaluated following repetitive stimulation, paired shock, animal asphyxiation and damage to the recording site. Longer latency potential changes were more labile to repetitive stimulation, paired shock and asphyxiation than short latency changes. The time course of the effects following experimental procedures was not equal for the potentials of different latencies. Most of the individual OT neurons studied were not affected by repetitive LC stimulation. However, a small percentage were enhanced and the remainder decreased discharge frequency. Hypertensive effects were ruled out as a cause of the OT unit responses following LC stimulation because the temporal course of both events were not similar. Results of both electrophysiological techniques suggest that the LC influences different neural elements and/or neural populations within the OT. These responses appear to be independent of one another.     

Interneuron circuits in the lateral geniculate nucleus of monocularly deprived cats.

This work investigated the function of interneurons and other types of cells in the lateral geniculate nucleus (LGN) in cats raised to adulthood with one eye sutured closed. In order to understand the basis of the commonly found deficit of Y-type relay cells in the deprived layers of the LGN, we looked for reduced or defective activity in other cells which also receive an afferent projection from Y-type ganglion cells in the visually deprived retina. Monocular deprivation did not produce a deficit in the activity of a class of interneurons which receive direct optic inputs from the same ganglion cells in the deprived eye that also drive the Y-type relay cells. Likewise, the Y-type afferent input from the deprived eye to XY-type relay cells was normal. The XY-type cells have mixed or hybrid receptive field properties and both X and Y excitatory inputs; although the Y-inputs to these cells are often much weaker than the X-inputs. The normal properties of Y-type interneurons and XY-type relay cells in the deprived LGN suggest that neither a retinal dysfunction nor an inherent inability of the Y-type optic tract axons to form adequate synapses onto LGN neurons are factors which would readily account for the reduction of Y-type relay cells in monocularly deprived cats. The hypothesis that the deprived Y-type relay cells may have difficulty in forming synaptic connections onto postsynaptic, binocular neurons was supported by observations of responses of cells in the perigeniculate region. Normally, perigeniculate neurons receive a strong binocular input from Y-type relay cells as well as an X-input in at least some cases. In binocular perigeniculate cells of the sutured cats, no inputs from deprived Y-type relay cells could be identified although a longer latency input, typical of that from X-type relay cells, was present.     

Locus coeruleus stimulation potentiates local inhibitory processes in rat cerebellum

We previously reported that a low threshold action of norepinephrine (NE) on the cerebellar circuitry is expressed as an amplification of the inhibitory action of gamma aminobutyric acid (GABA) on Purkinje cell activity. Here we examined the effects of locus coeruleus (LC) stimulation on “off-beam” inhibitions of Purkinje cell firing induced by activation of local basket and stellate cell interneurons to determine whether endogenous NE, released from synaptic terminals, could induce a comparable enhancement of GABA-mediated synaptic input to these neurons. Stimulation of LC, at current intensities which by themselves were subthreshold for directly affecting background activity of Purkinje neurons, markedly increased off-beam inhibitory neuronal responses. Iontophoretic application of the beta-adrenergic blocker sotalol reversibly antagonized this enhancement of synaptic inhibition. In comparison, the potentiative effects observed with LC stimulation were increased by iontophoresis of the alpha-adrenergic blocker phentolamine. LC -induced increases in off-beam inhibition were not observed after destruction of cerebellar noradrenergic terminals by 6-hydroxydopamine. These results suggest that noradrenergic input from the LC can augment the efficacy of conventional GABA-mediated inputs synapsing on the Purkinje cell.     

Locus coeruleus stimulation potentiates Purkinje cell responses to afferent input: The climbing fiber system

In cerebellum, the evoked responses of the Purkinje cell to both excitatory and inhibitory afferent input have previously been shown to be enhanced by local iontophoresis of norepinephrine (NE). The influence of locus coeruleus (LC) conditioning stimulation on Purkinje cell responses to climbing fiber input was examined to determine whether endogenous NE, released from synaptic terminals, could exert similar potentiative effects. Stimulation of LC, at intensities which by themselves were subthreshold for directly affecting background activity, markedly enhanced complex spike excitation of Purkinje cells elicited by activation of climbing fiber inputs from sensorimotor cortex. Depressant responses observed after complex spike excitation were also augmented by the LC conditioning. Iontophoretic application of sotalol, a specific β-adrenergic receptor blocker, reversibly antagonized this facilitation of climbing fiber-evoked responses. In addition, the potentiative effects of LC stimulation were not observed after destruction of NE-containing axons and terminals in cerebellum by 6-OHDA. These results suggest that noradrenergic input from the LC can enhance the efficacy of climbing fiber synaptic action on the Purkinje cell, and are thus consistent with the hypothesis of a ‘modulatory’ role rather than a specific information transfer function for NE in cerebellum.     

The effect of electrical stimulation of the locus coeruleus on the neuronal activity of the parietal associative cortex

In experiments performed on cats operated under ketamine anaesthesia and subsequently immobilized by myorelaxin it was demonstrated that locus coeruleus (LC) being stimulated by a train of pulses can exert influence on 79% of parietal cortex neurons. Inhibition of the background activity for 300-700 ms or a decrease in its frequency by 16-32% were observed in them after the LC stimulation. During intracellular recording neurons with background activity and "silent" neurons responded to LC stimulation by hyperpolarization (5-7 mV) lasting for 120-500 ms with latency of 30-90 ms. The duration of the inhibitory pause in background activity caused by transcallosal stimulation increased by 50-200 ms due to conditioning stimulation of LC. The duration of IPSPs evoked by transcallosal stimulation also increased by 50-100 ms under the influence of LC stimulation. It is concluded that the influence of LC stimulation on the activity of the parietal cortex neurons can be exerted either directly as inhibition of background activity and hyperpolarization or as modulation of effects of other neurotransmitters.     

Locus Coeruleus Stimulation Modulates the Nociceptive Response in Parafascicular Neurons: An Analysis of Descending and Ascending Pathways

The nociceptive responses in parafascicular neurons (PF) were recorded and studied following electrical stimulation of locus coeruleus (LC) combined with intrathecal (IT) or intracerebroventricular (ICV) administration of phentolamine (Ph), an

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-adrenoceptor antagonist. The results revealed the following. (1) Three different PF neuronal populations were observed according to their response pattern following noxious stimulation: nociceptive-on, nociceptive-off, and nonresponsive units. Only the nociceptive-on units were studied further. (2) The nociceptive discharges in majority of PF neurons (66/87) were inhibited by electrical stimulation of the LC. (3) The inhibitory effect of LC stimulation was prevented and even reversed by pretreatment of IT Ph (40 nmol) in 22 units, or by dorsolateral funiculi transection in 24 units tested. (4) The inhibitory effect of LC stimulation was strengthened by preadministration of ICV Ph (40 nmol) in 17 units tested. (5) ICV administration of norepinephrine (NE 30 nmol) resulted in PF neurons a biphasic response to nociceptive stimulation: an early brief inhibition and a late long-lasting facilitation. (6) Pretreatment of ICV Ph (40 nmol) prior to NE injection prevented the NE-induced biphasic response. The results suggest that stimulation of LC modulates the nociceptive response of PF neurons through both ascending and descending routes. These two diverse routes exert two different effects: a predominantly inhibitory role on the nociceptive transmission at the spinal cord level by descending NE-ergic fibers, and a facilitatory role on the responsiveness of PF to noxious inputs by ascending fibers.     

Beta-receptor involvement in locus coeruleus-induced inhibition of spinal trigeminal nucleus neurons: Microiontophoretic and HRP studies

Microiontophoretic and HRP studies were performed on cats anesthetized with alpha-chloralose to determine whether or not the locus coeruleus (LC)- and noradrenaline (NA)-induced inhibition of relay neurons in the subnucleus oralis of the spinal trigeminal nucleus (STN) is mediated by beta-adrenergic receptors. The inhibition of orthodromic spike generation upon intracranial trigeminal nerve stimulation by LC conditioning stimulation and microiontophoretically applied NA (100-200 nA) was antagonized during microiontophoretic application of sotalol, a beta-adrenergic antagonist, but not affected by phentolamine, an alpha-adrenergic antagonist. When HRP at doses of 300-500 nA was applied for 5-15 min to the immediate vicinity of the STN relay or interneuron, which was electrophysiologically identified by stimulating the ipsilateral trigeminal nerve and contralateral medial lemniscus, the injection site was localized to an area 0.3 mm in diameter and HRP-reactive cells were found in the ipsilateral LC, dorsal raphe nucleus and periaqueductal gray ventral to the aqueduct. These results strongly suggest that NA released from the nerve terminals of LC cells inhibits transmission in the STN relay neuron via beta-adrenergic receptors.     

Locus coeruleus-induced inhibition of dorsal cochlear nucleus neurons in comparison with lateral vestibular nucleus neurons

The effects of conditioning stimulation of the locis coeruleus (LC) on the neuron activity of dorsal cochlear nucleus (DCN), which is rich in noradrenergic nerve terminals, were compared with those on the lateral vestibular nucleus (LVN), devoid of such terminals, to determine whether or not noradrenaline is responsible for the LC-induced inhibition. The conditioning stimuli applied to the LC had no effect on either the field potential or the spike generation of mono- and polysynaptic neurons in the LVN elicited by VIIIth cranial nerve stimulation. In contrast, the spike firing of the DCN neurons with VIIIth cranial nerve stimulation was significantly inhibited by LC conditioning stimulation. The inhibition of spike generation was mainly observed in the DCN neurons which fired spikes with a longer latency. The inhibition of DCN neurons by LC conditioning stimulation did not occur in the cats pretreated with reserpine; however, a rapid recovery of the inhibition was produced by intraventricular application of noradrenaline. These results are in good agreement with the histochemical findings and support our previous conclusion that noradrenaline acts as an inhibitory transmitter or modulator on the nuclei where noradrenergic nerve terminals derived from the LC are located. In addition, the vestibular input in the primary relay nucleus is apparently not regulated by noradrenaline originating in the LC.     

Locus coeruleus modulation of the motor thalamus: Inhibition in nuclei ventralis lateralis and ventralis anterior

Single-cell recordings were made from 693 cells in thalamic nuclei ventralis lateralis and ventralis anterior (VL-VA). Cells were identified as thalamocortical projection cells by antidromic firing from motor cortex or classified according to responsiveness to stimulation of the brachium conjunctivum (BC), entopeduncular nucleus, and motor cortx. Only 14% of the cells tested responded to entopeduncular nucleus stimulation, whereas BC and motor cortex (orthodromic) stimulation each evoked responses in 31% of the VL-VA cells tested. The most common sources of convergent input to VL-VA cells were motor cortex and BC. In 30% of the VL-VA population tested, spontaneous firing was inhibited by stimulation of the locus coeruleus (LC). This inhibition had a long latency to onset which varied from cell to cell (100 to 1000 ms or more) and a long duration (mean = 1183 ms). The inhibition of spontaneous firing by LC was associated with a variable effect upon BC-evoked excitatory responses in VL-VA cells. In some cases, BC evoked responses were suppressed, but not abolished. In other cells, the excitatory response to BC was unaffected despite complete cessation of VL-VA cell spontaneous firing after LC stimulation. The inhibitory action of LC was not limited to any class of VL-VA cells, but occurred most frequently in neurons receiving an input from the BC. The LC inhibition of VL-VA is not related to changes in systemic blood pressure or an action at the level of the cerebellar cortex. However, LC also produces inhibitory and excitatory effects in centrum medianum neurons, which could account for some of the long-latency responses observed in VL-VA. This electrophysiological study of the action of locus coeruleus upon cellular activity in the motor thalamus argues against involvement in phasic movement and associated postural adjustments. Rather, the locus coeruleus projection to thalamus has properties which suggest a role in longer-term tonic regulation of motor activity.