Locus coeruleus activity in vitro: intrinsic regulation by a calcium-dependent potassium conductance but not alpha 2-adrenoceptors

Locus coeruleus neurons recorded intracellularly in rat brainstem slices exhibited spontaneous activity and a marked afterhyperpolarization following a burst of spikes. This afterhyperpolarization was associated with an increase in membrane conductance and resulted in a marked postactivation inhibition of spontaneous activity. Since the reversal potential of the afterhyperpolarization was found to be virtually identical when recorded with KCl or potassium acetate-filled electrodes and shifted in the hyperpolarizing and depolarizing direction with decreases and increases in extracellular potassium concentrations, respectively, the afterhyperpolarization seen following a burst of spikes in this cell group appears to be mediated by an increase in potassium conductance. The afterhyperpolarization and postactivation inhibition were markedly attenuated by reducing calcium influx by either omitting extracellular calcium in the bathing medium or blocking calcium channels with manganese or cadmium. Thus, the afterhyperpolarization and the resulting postactivation inhibition appear to be largely mediated by the activation of a calcium-dependent potassium conductance. Previous reports in vivo have suggested that activation of alpha 2-adrenoceptors by norepinephrine release from recurrent axons or dendrites may mediate self-inhibition in the locus coeruleus. In this study, we examined the effect of blocking alpha 2-adrenoceptors on the afterhyperpolarization and postactivation inhibition. Administration of the alpha 2-adrenoceptor antagonist piperoxane failed to produce any changes in either of these parameters, suggesting that at least in vitro the afterhyperpolarization and postactivation inhibition seen in locus coeruleus neurons do not result from the activation of alpha 2-adrenoceptors.     

Intracellular studies on the role of calcium in regulating the activity and reactivity of locus coeruleus neurons in vivo

EGTA, a specific calcium chelator, was injected intracellularly into presumed noradrenergic neurons of the rat locus coeruleus to evaluate the importance of calcium-dependent processes in regulating the activity and reactivity of these cells in vivo. The amplitude and duration of postactivation after hyperpolarizations induced by intracellular depolarizing pulses were markedly reduced in EGTA-treated cells; this change was associated with: (1) an increase in spontaneous firing rate; (2) a reduction in postactivation inhibition of firing; and (3) an increased reactivity to sensory stimulation. In control cells the reversal potential of the after hyperpolarization was at least 25 mV below 'resting' levels, indicating that an increase in potassium conductance was probably involved. Since EGTA virtually abolished the after hyperpolarization, the data are consistent with the concept that the after hyperpolarization is mediated by a calcium-activated potassium current. A calcium-dependent release of norepinephrine acting via alpha 2-adrenoceptors might also contribute to the after hyperpolarization. In conclusion, the influx of calcium into locus coeruleus neurons appears to serve a negative feedback function in the regulation of both spontaneous activity and reactivity to orthodromic stimulation.     

Peripheral GABAergic inhibition of spider mechanosensory afferents

Spider mechanosensory neurons receive an extensive network of efferent synapses onto their sensory dendrites, somata and distal axonal regions. The function of these synapses is unknown. Peripheral synapses are also found on crustacean stretch-receptor neurons but not on mechanosensory afferents of other species, although inhibitory GABAergic synapses are a common feature of centrally located axon terminals. Here we investigated the effects of GABA receptor agonists and antagonists on one group of spider mechanosensory neurons, the slit sense organ VS-3, which are accessible to current- and voltage-clamp recordings. Bath application of GABA activated an inward current that depolarized the membrane and increased the membrane conductance leading to impulse inhibition. VS-3 neuron GABA receptors were activated by muscimol and inhibited by picrotoxin but not bicuculline, and their dose-response relationship had an EC(50) of 103.4 microm, features typical for insect ionotropic GABA receptors. Voltage- and current-clamp analysis confirmed that, while the Na(+) channel inhibition resulting from depolarization can lead to impulse inhibition, the increase in membrane conductance (i.e. 'shunting') completely inhibited impulse propagation. This result argues against previous findings from other preparations that GABA-mediated inhibition is caused by a depolarization that inactivates Na(+) conductance, and it supports those findings that assign this role to membrane shunting. Our results show that GABA can rapidly and selectively inhibit specific mechanoreceptors in the periphery. This type of peripheral inhibition may provide spiders with a mechanism for distinguishing between signals from potential prey, predators or mates, and responding with appropriate behaviour to each signal.     

Postnatal development of alpha-adrenoceptor-mediated autoinhibition in the locus coeruleus

Rats, from birth to postnatal day 34, were anesthetized with urethane and a neuropharmacological study was carried out of the autoreceptors located on the somadendritic membranes of locus coeruleus (LC) neurons. Iontophoretic application of noradrenaline (NA) caused inhibition of LC cell firing at all developmental stages, and such inhibition was totally blocked by the alpha 2-antagonist piperoxane. The sensitivity of LC neurons to iontophoretically applied NA appeared to become reduced with age. In LC neurons from birth to postnatal day (PD) 8, the prolonged period of suppressed firing after antidromic activation by stimulation of the dorsal noradrenergic bundle was not shortened by piperoxane. After PD 9, the proportion of LC neurons in which piperoxane could antagonize the postactivation inhibition increased with age. These results indicated that although LC neurons, even at birth, had alpha 2-adrenoceptors on the somadendritic membranes which were responsible for the NA-induced inhibition, inhibition of LC cell firing caused by NA released from the terminals of axon collaterals and/or possibly from dendrodendritic synapses did not occur until PD 9.     

Antidromic activation of rat dorsomedial hypothalamic neurons from locus coeruleus and median eminence

In rats anesthetized with urethane, single unit activity was recorded in the hypothalamic dorsomedial nucleus (DMH) to obtain antidromic response to stimulation of locus coeruleus (LC) and median eminence (ME). Ninety-two cells were activated antidromically from LC and/or ME. Antidromic latencies to LC stimulation ranged from 7 to 39 msec and those to ME stimulation ranged from 5 to 20 msec. Approximately 13% of the neurons recorded revealed antidromic responses simultaneously from LC and ME, and they were found to bifurcate near the soma. The majority of DMH neurons projecting to LC alone were not spontaneously active, while those projecting to ME tended to discharge spontaneously.     

Relationship between large conductance calcium-activated potassium channel and bursting activity

To elucidate the role of the large conductance calcium-activated potassium channel (BK_Ca channel) in the production of bursting activity, which is characteristic of convulsions, effects of iberiotoxin (IbTX), a selective blocker of the BK_Ca channel, on bursting activity, induced by various procedures were examined using primary cultured neurons from the cerebral cortex of mice. IbTX completely inhibited bursting activity induced by pentylenetetrazol (PTZ), caffeine, 1,4,5-triphosphate (IP3) and direct forced increase of intracellular calcium. Inherent spontaneous bursting activity in the cerebral cortical neurons of the El mouse, which shows a high susceptibility to convulsions was also completely inhibited by IbTX. Apamin, a specific blocker of the small conductance calcium-activated potassium channel (SK_Ca channel) showed no inhibition of bursting activity. These findings suggest that the BK_Ca channel is essential for the production of bursting activity, and also suggest the possibility of clinical use of blocking agents of the BK_Ca channel against intractable epilepsy.     

Hypocretin/orexin depolarizes and decreases potassium conductance in locus coeruleus neurons

Recent studies demonstrated that noradrenergic locus coeruleus (LC) neurons are a particularly strong target of the novel neuropeptide, hypocretin (orexin). The present study sought to elucidate the action of hypocretin-B (HCRT) on LC neurons recorded intracellularly in rat brain slices. Bath (1.0 microM) or local puff application (50-100 microM in pipette) of HCRT depolarized LC neurons in rat brain slices and increased their spontaneous discharge rate. Depolarization evoked by HCRT was persistent in the presence of tetrodotoxin (TTX, 1 microM) and Co2+ (1 mM), indicating that HCRT directly activated LC neurons, and that its effect on the postsynaptic cell was not due to activation of TTX-sensitive sodium channels or Co2+-sensitive calcium channels. The apparent input resistance was significantly increased in the majority of LC neurons during the HCRT-evoked depolarization. Moreover, the HCRT-evoked depolarization was decreased in amplitude with hyperpolarization of membrane. The present results indicate that decreased potassium conductance is involved in the effect of HCRT on LC neurons.     

Inhibition of neuronal activity of the substantia nigra by noxious stimuli and its modification by the caudate nucleus

In urethane-anesthetized rats discharges of neurons of substantia nigra, pars compacta (SNC) were recorded extracellularly after natural somatic sensory stimulation and electrical stimulation of peripheral sensory nerves.

(1) Among different modalities of somatic sensory stimulation tested, noxious stimuli were effective in reducing spontaneous discharges of SNC neurons. The inhibition appeared with a concomitant increase of spike amplitude. The same inhibitory effect was obtained by stimulating the sciatic nerve (SC) repetitively. In response to single shock stimulation of the SC the inhibition occurred at an average latency of 39.6 msec (S.E. 1.6 msec) and lasted for 221.6 msec on average (S.E. 10.8 msec).

(2) The SC-induced inhibition of SNC neurons failed to reliably block orthoand antidromic discharges evoked from the caudate nucleus (Cd).

(3) In rats with the Cd lesioned the SC-induced inhibition was longer lasting than in controls. When the Cd was stimulated concurrently with SC stimulation, the inhibition from the SC was weakened.

(4) In a majority of SNC neurons, their inhibition by SC stimulation was antagonized by intravenous injection of haloperidol.

Locus ceruleus discharge characteristics of morphine-dependent rats: effects of naltrexone

Spontaneous and sensory-evoked discharge was recorded from locus ceruleus (LC) neurons of halothane-anesthetized rats that were chronically administered morphine. LC spontaneous discharge rates of morphine-treated rats were comparable to those of rats chronically administered saline. Administration of 1.0 micrograms morphine (i.c.v.), a dose which completely inhibits LC discharge of morphine-naive rats, had no effect on LC spontaneous discharge of morphine-treated rats, demonstrating that opiate tolerance had developed. Naltrexone, 0.3 and 1.0 microgram i.c.v., produced increases in LC spontaneous discharge rates that were 172 and 166% greater than baseline, respectively. Additionally, naltrexone disrupted LC discharge evoked by repeated sciatic nerve stimulation such that evoked discharge was decreased with respect to tonic discharge, and postactivation inhibition was attenuated. Naltrexone did not alter spontaneous or sensory-evoked LC discharge of rats chronically administered saline indicating that these neuronal effects are specific to opiate withdrawal. Pretreatment of rats with dexamethasone, or with an antagonist of corticotropin-releasing factor (CRF), alpha-helical CRF, did not attenuate the effects of naltrexone on LC discharge of morphine tolerant rats. The present study confirms other reports of LC activation associated with antagonist precipitated opiate withdrawal in vivo, and extends these observations by characterizing the disruptive effect of opiate withdrawal on the response of LC cells to phasically presented sensory stimuli, and demonstrating that the withdrawal response is not mediated by release of endogenous CRF.     

Effects of apamin on the discharge properties of putative dopamine-containing neurons in vitro

An in vitro brain slice preparation was used to evaluate the effects of apamin, a selective inhibitor of calcium-activated potassium channels, on the discharge characteristics of presumed dopamine-containing neurons within the substantia nigra. Apamin administration (1 μM) was associated with an increase in neuronal excitability as evidenced by the emergence of both sustained irregular and intermittent bursting activity similar to that seen spontaneously in vivo. These data suggest that the characteristic regular activity observed among putative dopamine-containing neurons in vitro is mediated, in part, by a calcium-activated potassium conductance.     

In vivo Intracellular Recording of Neurons in the Supraoptic Nucleus of the Rat Hypothalamus

Intracellular recordings were made from cells in the hypothalamic supraoptic nucleus in the urethane-anaesthetized male rat using the ventral surgical approach. Impalements lasted from 5 min to 1 h and recorded cells had an input resistance of 55 to 170 megohms. Spikes of over 50 mV were recorded from 14 cells which could be antidromically activated by stimulation of the neural stalk. The spikes showed a hyperpolarizing afterpotential and the broadening characteristic of rapidly firing magnocellular neurons, which recovered rapidly (<200 ms). When depolarized, the cells showed evidence of a transient potassium current. Recurrent synaptic coupling between the recorded cell and adjacent cells would be expected to alter the hyperpolarizing afterpotential of an antidromic spike as compared with a spontaneous spike; no perceptible difference in the waveforms of the different types of spike could be detected in 11 spontaneously active cells. Application of just subthreshold stimuli to the neural stalk did not evoke depolarizing or hyperpolarizing potentials. Suprathreshold shocks to the neural stalk, when the antidromic spike was prevented by collision, also had no discernible effect on membrane potential. Thus intracellular recordings from magnocellular neurons in vivo revealed electrophysiological properties similar to those seen in vitro. No evidence for synaptic interconnection between magnocellular neurons was found in male rats.     

Calcium-activated potassium channels in rat visceral sensory afferents

The purpose of the present study was to describe, at the single-channel level, the activity of a calcium-sensitive potassium channel in rat visceral-sensory neurons which has been suggested to be involved in sensory neuron excitability. Single-channel recordings in the inside-out configuration identified a 220 pS conductance calcium-activated potassium channel (KCa). From a −20 mV holding potential, increasing [Ca²⁺]_i from 0.01 μM to 1.0 μM increased the open probability of this channel 92% (from 0.12 to 0.23). However, from a +20 mV holding potential, increasing [Ca²⁺]_i from 0.01 to 1.0 μM increased the open probability by 326% (from 0.15 to 0.64). In addition, this large conductance KCa channel was blocked by TEA (1.0 μM) and charybdotoxin (40 μM) when applied to the external surface. These results are the first to characterize a large conductance KCa channel in the sensory afferent neurons of the rat nodose ganglia and should further expand the understanding to the ionic currents involved in the regulation of sensory afferent neuronal activity.     

Burst firing in midbrain dopaminergic neurons

Midbrain dopaminergic (DA) neurons fire bursts of activity in response to sensory stimuli, including those associated with primary reward. They are therefore conditional bursters – the bursts conveying, amongst other things, motivationally relevant information to the forebrain. In the forebrain, bursts give rise to a supra-additive release of dopamine, and possibly favour the release of co-localised neuropeptides. Evidence is presented that in rat DA neurons, bursts are engendered by the activity of cortically-regulated afferents. Certain factors are identified which, in combination, lead to burst production: (1) A burst of activity in EAAergic afferents to DA neurons arising from non-cortical sources, but controlled by the medial prefrontal cortex; (2) N-methyl-

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-aspartate receptor activation, producing a slow depolarising wave in the recipient neuron; (3) activation of a high threshold, dendritically located calcium conductance which produces a ‘plateau potential'; (4) activation of a calcium-activated potassium conductance, which terminates the burst. These factors are argued to operate in the context of an ‘optimal' level of intracellular calcium buffering for bursting. Other factors which appear to be involved in bursting in other systems, in particular a low threshold calcium conductance, are rejected as being necessary for bursting in DA neurons. The factors which do play a crucial role in burst production in DA neurons are integrated into a theory from which arises a series of hypotheses amenable to empirical investigation. Additional factors are discussed which may modulate bursting. These may either act indirectly through changes in membrane potential (or intracellular calcium concentration), or they may act directly through an interaction with certain conductances, which appear to promote or inhibit burst firing in DA neurons.     

Neuronal responses of the rat amygdala during extinction and reassociation learning in elementary and configural associative tasks

To investigate functional heterogeneity within the amygdala in appetitive conditioned instrumental behaviours, neuronal activity was recorded from the amygdala of behaving rats during learning and discrimination of conditioned sensory stimuli associated with or without reinforcement [sucrose solution, intracranial self-stimulation (ICSS)]. Sensory stimuli included auditory (tone), visual (light) and configural (simultaneous presentation of tone and light) stimuli. The rat was trained to lick a spout protruded close to its mouth just after a conditioned sensory stimulus to obtain a reward. Of the 609 neurons recorded from the amygdala and amygdalostriatal transition area, 154 responded to one or more sensory stimuli. The 62 amygdalar neurons responded strongly to certain conditioned sensory stimuli associated with rewards. Of these 62 neurons, 45 were tested with the extinction trials. Responses of 31 neurons to conditioned stimuli were finally extinguished, and those of the remaining 14 were not extinguished. Furthermore, responses of 26 of these 31 neurons resumed in the relearning trials (plastic neurons), suggesting that these sensory responses were associative rather than just responses to physical properties of the stimuli. These plastic neurons were located mainly in the basolateral nucleus of the amygdala, and responses of the plastic neurons were correlated with behavioural responses. These results suggest that the basolateral nucleus is crucial in associative learning between sensory information and affective significance for behavioural outputs in appetitive conditioned instrumental behaviours.     

Phase-dependent Modulation of a Cutaneous Sensory Pathway by Glycinergic Inhibition from the Locomotor Rhythm Generator in Xenopus Embryos

In immobilized Xenopus laevis embryos two classes of sensory interneuron are excited by mechanosensory Rohon - Beard neurons and rhythmically inhibited during fictive swimming. Dorsolateral commissural (DLC) interneurons are inhibited in time with rhythmic motor discharge on the same side as their soma, while unidentified dorsolateral (DLX) interneurons are inhibited in the opposite phase of the swimming rhythm. The inhibition is abolished by bath application of strychnine sulphate at 1 - 10 microM, but not by the gamma-aminobutyric acid antagonists bicuculline (20 - 40 microM) or curare (70 - 100 microM). The inhibitory postsynaptic potentials (IPSPs) involve an increase in chloride conductance since they are reversed in sign to become depolarizing following intracellular injection of chloride ions. The conductance increase during inhibition was able to block impulses evoked by intracellular current in a phase-dependent manner, suggesting that postsynaptic inhibition is sufficient to account for the gating of afferent input to the spinal cord during swimming. An interneuron receives IPSPs that are predominantly in one phase of the rhythm, but most interneurons are also inhibited sporadically in the opposite phase. The amplitude and time course of the IPSPs closely follow the frequency of the swimming rhythm, with maximal inhibition occurring near the starts of episodes, when swimming frequency is at its highest. Towards the end of an episode, when swimming frequency declines, the level of inhibition is low, the membrane potential of the interneurons returns to rest between cycles, and IPSPs often fail to occur. Inhibition suppresses sensory excitation in a phase-dependent manner (cf. Sillar and Roberts, Nature, 331, 262 - 265, 1988). Sensory interneurons fire a single impulse in response to a brief sensory stimulus, but they will usually fire multiple impulses when depolarized with sufficient intracellular current. In some sensory interneurons a short-latency IPSP follows the impulse evoked by skin stimulation that could curtail impulse activity. However, when the inhibition is blocked by strychnine, sensory interneurons still fire a single short-latency impulse, favouring the conclusion that brief, synchronized afferent excitation elicits a single impulse in neurons that are capable of firing multiply. Since the inhibition of DLC interneurons occurs in phase with activity on the same side it probably originates from spiking in ipsilateral glycinergic commissural interneurons which have ipsilateral as well as contralateral projections. The inhibition of DLX interneurons in the opposite phase probably originates from the contralateral projections of commissural interneurons.     

Characterization of large conductance Ca2+-activated K+ channels in cerebellar Purkinje neurons

We investigated the role of large conductance, calcium-activated potassium channels (BK channels) in regulation of the excitability of cerebellar Purkinje neurons. Block of BK channels by iberiotoxin reduced the afterhyperpolarization of spontaneous action potentials in Purkinje neurons in acutely prepared cerebellar slices. To establish the conditions required for activation of BK channels in Purkinje neurons, the dependence of BK channel open probability on calcium concentration and membrane voltage were investigated in excised patches from soma of acutely prepared Purkinje cells. Single channel currents were studied under conditions designed to select for potassium currents and in which voltage-activated currents were largely inactivated. Micromolar calcium concentrations activated channels with a mean single channel conductance of 266 pS. BK channels were activated by both calcium and membrane depolarization, and showed no sign of inactivation. At a given calcium concentration, depolarization over a 60-mV range increased the mean open probability (P(O)) from < 0.1 to > 0.8. Increasing the calcium concentration shifted the voltage required for half maximal activation to more hyperpolarized potentials. The apparent affinity of the channels for calcium increased with depolarization. At -60 mV the apparent affinity was approximately 35 micro m decreasing to approximately 3 micro M at +40 mV. These results suggest that BK channels are unlikely to be activated at resting membrane potentials and calcium concentrations. We tested the hypothesis that Purkinje cell BK channels may be activated by calcium entry during individual action potentials. Significant BK channel activation could be detected when brief action potential-like depolarizations were applied to patches under conditions in which the sole source of calcium was flux across the plasma membrane via the endogenous voltage-gated calcium channels. It is proposed that BK channels regulate the excitability of Purkinje cells by contributing to afterhyperpolarizations and perhaps by shaping individual action potentials.     

Differential effects of apamin- and charybdotoxin-sensitive K+ conductances on spontaneous discharge patterns of developing retinal ganglion cells.

The spontaneous discharge patterns of developing retinal ganglion cells are thought to play a crucial role in the refinement of early retinofugal projections. To investigate the contributions of intrinsic membrane properties to the spontaneous activity of developing ganglion cells, we assessed the effects of blocking large and small calcium-activated potassium conductances on the temporal pattern of such discharges by means of patch-clamp recordings from the intact retina of developing ferrets. Application of apamin and charybdotoxin (CTX), which selectively block the small and large calcium-activated potassium channels, respectively, resulted in significant changes in spontaneous firings. In cells recorded from the oldest animals [postnatal day 30 (P30)-P45], which manifested relatively sustained discharge patterns, application of either blocker induced bursting activity. With CTX the bursts were highly periodic, short in duration, and of high frequency. In contrast, with apamin the interburst intervals were longer, less regular, and lower in overall spike frequency. These differences between the effects of the two blockers on spontaneous activity were documented by spectral analysis of discharge patterns. Filling cells from which recordings were made with Lucifer yellow revealed that these effects were obtained in all three morphological classes of cells: alpha, beta, and gamma. These findings provide the first evidence that apamin- and CTX-sensitive K+ conductances can have differential effects on the spontaneous discharge patterns of retinal ganglion cells. Remarkably, the bursts of activity obtained after apamin application in more mature neurons appeared very similar to the spontaneous bursting patterns observed in developing neurons. These findings suggest that the maturation of calcium-activated potassium channels, particularly the apamin-sensitive conductance, may contribute to the changes in spontaneous firings exhibited by retinal ganglion cells during the course of normal development.     

Stimulus-specific oscillatory responses of the brain: a time/frequency-related coding process.

OBJECTIVES: To review the coherent, rhythmic oscillations above approximately 20 Hz that occur in response to sensory inputs in the firing rate and membrane or local field potentials of distributed neuron aggregates of CNS layered structures.RESULTS: Oscillatory activity at approximately 20-80 Hz occurs in response to either olfactory, auditory and visual (contrast) stimuli; oscillations at frequencies centered on 100-120 Hz or 600 Hz are recorded, respectively, from the visual system (luminance stimulation) and from the somatosensory cortex. Experimental evidence suggests sources/mechanisms of generation that depend on inhibitory interneurons and pyramidal cells and are partially independent from those of conventional (broadband) evoked responses. In the olfactory and visual systems, the oscillatory responses reflect the global stimulus properties. A time/phase correlation between firing rate, spiking coincidence and oscillatory field responses has been documented. The oscillatory responses are postsynaptic both in cortex and in precortical structures (e.g. retina; LGN). Evidence indicates intracortical and thalamocortical interacting mechanisms of regulation as well as GABAergic and cholinergic modulation. In the visual cortex the oscillatory responses are driven by oscillations in the synaptic input. Oscillatory potentials are dependent on resonance phenomena and produce narrow-band synchronization of activated neurons. They may have a role in the 'binding' of separate neuronal aggregates into sensory units. CONCLUSIONS: Oscillatory responses contribute as a time/frequency coding mechanism to pacing neurons selectively for the physical properties of stimulus and are involved in sensory information processing.     

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.     

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.