Eiichi Jodo

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.

Potent excitatory influence of prefrontal cortex activity on noradrenergic locus coeruleus neurons

An influence of the prefrontal cortex on noradrenergic locus coeruleus neurons would have profound implications for the function of the locus coeruleus system. Although the medial prefrontal cortex does not substantially innervate the core of the nucleus locus coeruleus, evidence indicates that the medial prefrontal cortex projects to regions containing locus coeruleus dendrites; indirect medial prefrontal cortex-locus coeruleus projections are also possible. Here, we examined influences of prefrontal cortex activity on locus coeruleus firing rates by activating or inactivating the medial prefrontal cortex while recording impulse activity of locus coeruleus neurons extracellularly in anaesthetized rats. Most of our electrical stimulation experiments were conducted in rats which underwent lesions of the ascending dorsal bundle of noradrenergic fibres from the locus coeruleus to eliminate locus coeruleus projections to the prefrontal cortex, because antidromic activation of locus coeruleus from the prefrontal cortex affects even non-driven locus coeruleus neurons through collaterals. Single pulse stimulation (1 mA, 0.3-0.5 ms) of the dorsomedial (frontal region 2) or prelimbic region of the medial prefrontal cortex synaptically activated 13/16 (81%) or 16/56 (29%) locus coeruleus neurons, respectively. Train stimulation (20 Hz for 0.5 s) synaptically activated greater percentages of locus coeruleus cells, 11/12 cells (92%) for the dorsomedial prefrontal cortex, and 41/50 cells (82%) for the prelimbic cortex. No inhibitory responses in the locus coeruleus were obtained with dorsomedial prefrontal stimulation, and weak inhibition was found in 16% of locus coeruleus cells with prelimbic stimulation. Electrical stimulation of more lateral frontal cortex (Fr1 area) had no effects on locus coeruleus activity. Chemical stimulation of the dorsomedial prefrontal cortex with L-glutamate (10 or 100 mM) or D,L-homocysteic acid (10 mM) phasically activated 15/26 (55%) locus coeruleus cells, and 15/68 cells (22%) with prelimbic stimulation; such activation was sometimes followed by long-lasting oscillatory activity. No locus coeruleus cells exhibited purely inhibitory responses with chemical stimulation of any prefrontal cortex site. Inactivation of the dorsomedial or prelimbic region of the prefrontal cortex with lidocaine microinjection (2%, 180 or 300 nl) reduced locus coeruleus firing rates in 6/10 (60%) or 7/19 (37%) locus coeruleus cells, respectively. In no case did lidocaine in any prefrontal cortex site activate a locus coeruleus neuron. These results indicate that the medial prefrontal cortex provides a potent excitatory influence on locus coeruleus neurons. The fact that inactivation of the medial prefrontal cortex suppressed locus coeruleus firing indicates that the medial prefrontal cortex also provides a resting tonic excitatory influence on locus coeruleus activity.

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.

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.

Activation of locus coeruleus by prefrontal cortex is mediated by excitatory amino acid inputs

We examined the role of excitatory amino acids (EAAs) in activation of noradrenergic locus coeruleus (LC) neurons evoked by electrical stimulation of the medial prefrontal cortex (mPFC) in halothane-anesthetized rats. Microinfusion of the specific N-methyl-D-aspartate antagonist 2-amino-5-phosphonopentanoic acid (AP5, 50 or 100 microM) into the LC significantly suppressed LC responses evoked by mPFC stimulation. Microinfusion of the selective non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 25 or 50 microM) also significantly reduced evoked LC responses. Simultaneous microinfusion of both AP5 and CNQX considerably increased the proportion of LC neurons which exhibited complete suppression of evoked responses (81%), compared to either AP5 or CNQX alone (approximately 50% each). These results indicate that LC activation by mPFC stimulation is mediated by both NMDA- and non-NMDA-type EAA channels.

Effects of practice on the P300 in a Go/NoGo task ☆

Previous studies have reported that there are differences in latency and scalp topography between Go-P300 and NoGo-P300 in a Go/NoGo task. This study investigated whether these differences could be observed after intensive practice. Subjects performed the task at 1 session (200 trials) per day for 6 days. In session 1, P300 latency was significantly later to the NoGo stimuli than to the Go stimuli, while in session 6 P300 latency was significantly shorter to the NoGo stimuli than to the Go stimuli. Reaction time (RT) was significantly shortened by practice, but P300 latency to the Go stimuli was not affected by practice. The scalp topography of the P300 was not varied by practice, having a parieto-central distribution to the Go stimuli, a centro-parietal one to the NoGo stimuli. These findings show that the temporal relation between Go-P300 and NoGo-P300 can be apparently reversed by practice. Since the Go-P300 differed from the NoGo-P300 in the effects of practice, our results suggest the possibility that the Go-P300 and the NoGo-P300 may be functionally separate P300 components.

Selective responsiveness of medial prefrontal cortex neurons to the meaningful stimulus with a low probability of occurrence in rats.

Multi-unit neuronal activity was recorded in the medial prefrontal cortex (mPFC) of 13 chronically prepared male rats while they performed a two-tone discrimination task. Tones at 1000 and 2000 Hz were sequentially presented at intervals of 3-6 s. The duration of each tone was 0.8 s. Rats were trained to press a bar within 1.2 s after the cessation of the 1000 Hz tone (target), and not to press the bar when the other tone (non-target) was presented. Intracranial electrical stimulation (ICS) of the medial forebrain bundle was given as a reward immediately after the rats had correctly responded to the target tone. Probability of the target occurrence was either 30% or 70% in different sessions. When the target tone was presented on only 30% of the trials, the mPFC neurons in the majority of rats tested (10/13) exhibited phasic excitation about 100 ms after the onset of the target tone. However, when the target tone occurred on 70% of the trials, mPFC neurons in most of rats (11/13) did not show excitatory responses, and in some of them (5/13) were inhibited. No mPFC neurons exhibited significant responses to the non-target tone, regardless of its probability. These results suggest that the mPFC neurons selectively respond to meaningful events with a low probability of occurrence.

Effects of acupuncture to the sacral segment on the bladder activity and electroencephalogram

Abstract Using urethane‐anaesthetized rats, the effects of acupunctural stimulation to the sacral segment on the urinary bladder activity and cortical electroencephalogram (EEG) were examined. The acupuncture suppressed urinary bladder activity in 36 of 68 trials. On many occasions (22/36 trials), suppression was accompanied by an increase in EEG amplitude. In such cases, the EEG power increased in all frequency bands after stimulation. The same EEG changes could be induced when the bladder was empty with no contraction. The results suggest that acupuncture stimulation affects both the bladder activity and sleep–arousal system.

The role of the hippocampo-prefrontal cortex system in phencyclidine-induced psychosis: A model for schizophrenia

Phencyclidine (PCP) is a psychotomimetic drug that induces schizophrenia-like symptoms in healthy individuals and exacerbates pre-existing symptoms in patients with schizophrenia. PCP also induces behavioral and cognitive abnormalities in non-human animals, and PCP-treated animals are considered a reliable pharmacological model of schizophrenia. However, the exact neural mechanisms by which PCP modulates behavior are not known. During the last decade several studies have indicated that disturbed activity of the prefrontal cortex (PFC) may be closely related to PCP-induced psychosis. Systemic administration of PCP produces long-lasting activation of medial PFC (mPFC) neurons in rats, almost in parallel with augmentation of locomotor activity and behavioral stereotypies. Later studies have showed that such PCP-induced behavioral abnormalities are ameliorated by prior administration of drugs that normalize or inhibit excess excitability of PFC neurons. Similar activation of mPFC neurons is not induced by systemic injection of a typical psychostimulant such as methamphetamine, even though behavioral hyperactivity is induced to almost the same level. This suggests that the neural circuits mediating PCP-induced psychosis are different to those mediating methamphetamine-induced psychosis. Locally applied PCP does not induce excitation of mPFC neurons, indicating that PCP-induced tonic excitation of mPFC neurons is mediated by inputs from regions outside the mPFC. This hypothesis is strongly supported by experimental results showing that local perfusion of PCP in the ventral hippocampus, which has dense fiber projections to the mPFC, induces tonic activation of mPFC neurons with accompanying augmentation of behavioral abnormalities. In this review we summarize current knowledge on the neural mechanisms underlying PCP-induced psychosis and highlight a possible involvement of the PFC and the hippocampus in PCP-induced psychosis.

P3b-like potential of rats recorded in an active discrimination task.

We investigated whether the potential corresponding to the human P3b could be recorded on the dura mater over the frontal cortex of the rat in an active discrimination task. Rats were trained to press a bar within 1200 msec after cessation of the target tone (1000 Hz) lasting for 800 msec, and to withhold an overt response to the standard tone (2000 Hz). Rats were given intracranial electrical stimulation to the medial forebrain bundle as a reward only when they correctly responded to the target tone. The stimulus probability of the target tone was manipulated at 3 levels: 30, 50 and 70% of all trials. Large, slow positive deflections with peak latency at about 400-500 msec were elicited to the target tone, which were preceded by a large negative potential with its peak around 180 msec, whereas such a clear deflection was not elicited to the standard tone irrespective of the stimulus probability. This positive slow deflection was very similar in morphology to the human P3, and this P3-like potential was significantly larger when the target tone was less frequent (30%) than in the case of more frequent targets (50 and 70%). These results suggest that a potential highly similar to P3b can be recorded in the rat, and that it may provide a useful model to investigate the neurophysiological basis of the human P3b.