Yukihiko Kayama

Relation of a negative ERP component to response inhibition in a Go/No-go task

Previous studies have suggested that a negative component (N2) of the event-related potential (ERP), whose peak latency is 200-300 msec after stimulus onset, may vary in amplitude depending on the neuronal activity required for response inhibition. To confirm this, ERPs were recorded in a Go/No-go paradigm in which subjects of one group (HI, n = 10) were asked to respond to Go stimuli with key pressing within a shorter period (less than 300 msec) than those of the other group (LI, n = 10) whose upper limit of the reaction time was relatively longer (less than 500 msec). All subjects had to withhold the Go response to the No-go stimuli without making overt muscle activities. The N2 component was recorded superposed on the initial descending limb of the P300 and other slow deflections, which were attenuated with a digital filter to measure the amplitude of N2. The N2 amplitude was significantly larger to the No-go stimulus than to the Go stimulus in both groups, but the N2 to the No-go stimulus was significantly larger in the HI group than in the LI group. These differences in N2 amplitude between conditions or groups were thought to be independent of other ERP components such as P300 and CNV. These results suggest that at least to some extent N2, which increased in amplitude when a greater effort was required to withhold the Go response, reflects the activity of a response inhibition system of the brain.

Firing of 'possibly' cholinergic neurons in the rat laterodorsal tegmental nucleus during sleep and wakefulness.

To clarify functional roles of mesopontine cholinergic neurons as a component of an activating system, single neuronal activity in the laterodorsal tegmental nucleus (LDT) of undrugged rats, whose head was fixed painlessly, was recorded along with cortical EEG and neck EMG. Activity of some dorsal raphe (DR) neurons was also recorded for comparison. Most of the animals had been sleep-deprived for 24 h. Observation was made only on neurons generating broad spikes, presumed from previous studies to be cholinergic or monoaminergic. The position of recorded neurons was marked by Pontamine sky blue ejected from the glass pipette microelectrode, and was identified on sections processed for NADPH diaphorase histochemistry which specifically stained cholinergic neurons. According to their firing rates during wakefulness (AW), slow-wave sleep (SWS) and paradoxical sleep (PS), 46 broad-spike neurons in the LDT were classified into 4 groups: (1) neurons most active during AW and silent during PS (some of these neurons might be serotonergic rather than cholinergic, as all the 9 neurons in the DR); (2) neurons most active during PS and silent during AW; (3) neurons equally more active during AW and PS than SWS; and (4) others mainly characterized by transiently facilitated activity at awakening and/or onset of PS. Neurons of groups 2 and 3 were the major constituents of the LDT. In most neurons change in firing preceded EEG change, except at awakening from PS. These results suggest that: (1) the LDT is composed of cholinergic neurons with heterogenous characteristics in relation to sleep/wakefulness; and (2) some tegmental cholinergic neurons play a privotal role in induction and maintenance of PS.

Effects of locus coeruleus stimulation on neuronal activities of dorsal lateral geniculate nucleus and perigeniculate reticular nucleus of the rat

In rats anesthetized with urethane, a stimulating electrode was introduced to the locus coeruleus by observing the antidromic field response to single shock stimulation of the dorsal pathway of noradrenergic axons. Effects of locus coeruleus stimulation were studied on activities of relay neurons and intrinsic interneurons of the dorsal lateral geniculate nucleus and on those of neurons in the perigeniculate reticular nucleus. The intrinsic interneurons and the perigeniculate reticular neurons are believed to exert inhibition upon the relay neurons. The relay neurons were activated by repetitive stimulation of locus coeruleus; spontaneous discharges were increased in rate and the threshold of response to single shock stimulation of the optic nerve was lowered. The activation was rarely seen in rats pretreated with alpha-methyl-p-tyrosine. Iontophoretic application of phentolamine, an alpha-blocker, effectively antagonized the activation, whereas an iontophoretic beta-blocker and cholinergic blockers were virtually ineffective. The activation of the relay neurons was suggested to be due to a direct action of noradrenaline, released by locus coeruleus stimulation. Locus coeruleus stimulation inhibited the interneurons and activated the perigeniculate reticular neurons; spontaneous or light-evoked discharges were suppressed in the interneurons and tonic discharges were elicited in the perigeniculate reticular neurons. These effects of locus coeruleus stimulation were mimicked by noradrenaline applied iontophoretically. Activation of the perigeniculate reticular neurons was antagonized by an iontophoretic alpha-blocker but not by a beta-blocker. Two special features emerge from the present results: (1) the locus coeruleus exerts different effects upon the two neuronal constituents of the dorsal lateral geniculate nucleus, excitation of the relay neurons and inhibition of the intrinsic interneurons; (2) a suggestion previously advocated that locus-coeruleus-induced excitation of the lateral geniculate relay neurons would be due to inhibition of inhibitory neurons (disinhibition) does not hold true, at least with respect to the perigeniculate reticular neurons; the latter neurons have been proved to exert a powerful inhibition upon the geniculate relay neurons and they are excited by stimulation of the locus coeruleus.

Analysis of recurrent inhibitory circuit in rat thalamus: neurophysiology of the thalamic reticular nucleus

*Department of Neurophysiology, Institute of Higher Nervous Activity, Osaka University Medical School, Kita-ku, Osaka 530, Japan ~fDepartment of Physiology, Akita University School of Medicine, Akita 010, Japan *Laboratory of Biological Science, Osaka Keizai University, Higashiyodogawa-ku, Osaka 533, Japan §Department of Physiology, Kanazawa Medical University, Uchinada, Ishikawa 920-02, Japan IIPhysiological Laboratory, Kinki University Faculty of Pharmacy, Higashi-Osaka 577, Japan

Acute administration of phencyclidine induces tonic activation of medial prefrontal cortex neurons in freely moving rats

Recent studies have reported that acute administration of the psychotomimetic drug phencyclidine results in considerable increases in the amounts of both extracellular glutamate and dopamine in the medial prefrontal cortex (mPFC). However, the effect of phencyclidine on the firing activity of mPFC neurons remains unknown. Here, we report the first data on phencyclidine-induced activation of mPFC neurons in freely moving rats. Unanesthetized rats received an intraperitoneal injection of either phencyclidine (5 mg/kg) or physiological saline (0.5 ml/kg) in order to investigate the impulse activity of mPFC neurons and behavioral activity. The phencyclidine injection induced a remarkable increase (two-fold or more) in the spontaneous discharge rate of the majority of mPFC neurons (20/23), and this increase lasted for more than 70 min. In addition, a considerable augmentation of behavioral activity was observed that nearly paralleled that of the mPFC neuronal activation. In contrast, microiontophoretically applied phencyclidine exerted little influence on the spontaneous firing activity of most mPFC neurons (25/29) in anesthetized rats, although systemically applied phencyclidine produced activation of mPFC neurons even under general anesthesia. These results suggest that the behavioral abnormalities induced by acute administration of phencyclidine may be caused by hyperactivation of mPFC neurons, and that this hyperactivation is elicited through excitatory inputs from brain regions outside the mPFC.

Mutual interactions among cholinergic, noradrenergic and serotonergic neurons studied by ionophoresis of these transmitters in rat brainstem nuclei

In urethane-anesthetized rats, single neuronal activity was recorded in or around the central gray of the caudal mesencephalon to rostral pons with multibarrel microelectrodes for ionophoretic application of acetylcholine, noradrenaline and serotonin. Neurons were classified by spike shape into broad-spike and brief-spike neurons. In the laterodorsal tegmental nucleus, locus coeruleus or dorsal raphe, broad-spike neurons, marked by Pontamine Sky Blue and discriminated in sections processed for histochemistry of reduced nicotinamide adenine dinucleotide phosphate diaphorase or Nissl staining, were presumed to be cholinergic, noradrenergic or serotonergic, respectively. The majority of these neurons were inhibited through autoreceptors, except some laterodorsal tegmental neurons which might not be furnished by autoreceptors. Noradrenaline and serotonin inhibited more than two-thirds of the laterodorsal tegmental neurons tested, while a few neurons were excited by noradrenaline. Though effects of noradrenaline on dorsal raphe neurons and those of serotonin on locus coeruleus neurons were not clear in many neurons tested, neurons affected in these examinations (30%) were all inhibited clearly and no excitatory effect was observed. Acetylcholine exerted inhibition on about one-half of dorsal raphe neurons, while effects of acetylcholine on locus coeruleus neurons were the only case in the present study in which excitation was the major effect, though more than a half of locus coeruleus neurons were not sensitive to this drug. Thus, in this study some new data on the pharmacological properties of the cholinergic laterodorsal tegmental neurons were obtained. In addition, mutual interactions between brainstem cholinergic, noradrenergic and serotonergic neurons were assayed by comparing the pharmacological properties of these neurons tested with a uniform procedure. The interactions between these diffuse projection neurons may be involved in neural mechanisms controlling vigilance, wakefulness and/or sleep.

Somatotopic organization in the rat thalamic reticular nucleus.

Mapping experiments were carried out to establish the somatotopic organization of the somatosensory part of the thalamic reticular nucleus (TR) of the rat. Different parts of the body were found to project somatotopically onto the S-TR. The rostral-to-caudal and the dorsal-to-ventral axes in the body parts were transformed into the ventral-to-dorsal and the caudal-to-rostral axes in the S-TR, respectively. The head and face occupied about two thirds of the S-TR, distributing in the ventral half and in the dorsocaudal part. Particularly a large area of the S-TR was devoted to the vibrissae, nose (rhinarium) and lip. The trunk was projected to a small area of the dorsal part. The projections of the hind- and forelimb were mainly in the dorsal part, the former being placed above the latter.

Effects of stimulating the dorsal raphe nucleus of the rat on neuronal activity in the dorsal lateral geniculate nucleus

The effect of stimulating the dorsal raphe nucleus (DRN) on the activity of single relay neurons in the dorsal lateral geniculate nucleus (LGNd) was studied in rats anesthetized with urethane. The position of stimulating electrodes was confirmed on histological sections processed with NADPH-diaphorase histochemistry which could delineate the DRN clearly. During repetitive stimulation of the DRN at 200 Hz for several to 10 seconds no consistent change in firing was observed, but between several and several tens of seconds after the cessation of stimulation spontaneous firing of LGNd neurons was suppressed. In many cases the suppression proceeded concomitantly with augmentation of slow waves in the cortical EEG. The suppression was mimicked by ionophoresis of serotonin, and antagonized by a serotonergic antagonist, methysergide. In addition, in animals in which DRN stimulation became ineffective after it was evoked many times, the suppression could be restored by intraperitoneal administration of a serotonin precursor, 5-hydroxytryptophan. Compilation of peristimulus time histograms revealed that a brief DRN stimulation (5 shocks at 1000 Hz) could also elicit the suppression lasting from 60 to 100 ms or longer after the shocks. These results suggest that serotonin released from terminals of DRN neurons exerts long-latency and long-lasting inhibition of LGNd relay neurons. Along with brainstem noradrenergic and cholinergic systems, the serotonergic projection from the DRN acts to control excitation levels of the forebrain.

Electrophysiology of ascending, possibly cholinergic neurons in the rat laterodorsal tegmental nucleus: comparison with monoamine neurons

In urethane-anesthetized rats single neuronal activity was recorded in the laterodorsal tegmental nucleus (LDT), which has a dense complement of cholinergic neurons, and in the dorsal raphe and locus coeruleus for comparison. Most LDT neurons responded antidromically to stimulation of either one or more of several rostral loci, and gave rise to broad spikes. They showed various properties very similar to those of monoaminergic neurons. Others generated brief spikes. The former may be cholinergic. The most frequent response of broad-spike LDT neurons to noxious stimulation was phasic excitation, which tended to become weak or disappear upon repetition.

Ascending, descending and local control of neuronal activity in the rat lateral geniculate nucleus.

Mechanisms of control for activities of relay neurons (P-cells) in the rat dorsal lateral geniculate nucleus (LGNd) are surveyed with special reference to ascending projection arising from the locus coeruleus (LC), the local projection from the visual portion of the thalamic reticular nucleus (vTRN) and the descending projection from the visual cortex (VC). Noradrenaline released from terminals of LC neurons exerts a facilitatory influence on P-cell activity via alpha-receptors. A recurrent projection of vTRN neurons on P-cells is inhibitory, utilizing GABA as a transmitter. P-cells receive an excitatory input from corticothalamic neurons of VC. However, in many P-cells the corticofugal excitation is counterbalanced by inhibition arising in vTRN neurons which are invariably exited by the collateral branches of the corticogeniculate axons. Thus, LGNd is not a simple relay station, but various modifications of visual information are made in this nucleus.