With long intervals, inter-stimulus interval is the critical determinant of the human P300 amplitude.

Previous research, using short inter-stimulus intervals (1-4 s), suggests that the P300 of the human event-related potential during oddball and single-stimulus tasks is mainly affected by target-to-target interval (TTI). The present study tested the validity of this claim at longer intervals in a learning task. Participants were assigned to either an oddball task with an inter-stimulus interval (ISI) of 9-20 s or a single-stimulus task with an ISI of 9-20 or 40-90 s and had to learn when to respond to the stimuli. In the oddball task, the target elicited larger amplitudes than did the standard. When comparing the stimuli from the short- and long-ISI conditions with the target from the oddball condition, it was found that the P300 was more positive at long-ISI stimuli than at short-ISI stimuli or oddball targets, and short-ISI stimuli and oddball targets elicited equally large P300 amplitudes. These results suggest that, in oddball tasks with long intervals, besides cognitive factors, ISI rather than TTI affects the P300 amplitude.

Differential modulation of hippocampal signal transfer by tuberomammillary nucleus stimulation in freely moving rats dependent on behavioral state.

Tuberomammillary histamine neurons (TM) in the posterior hypothalamus project to extensive parts of the brain, including the hippocampal formation. The purpose of the present experiments was to investigate whether activation of the TM modulates signal transfer from the perforant pathway (PP) or ventral hippocampal commissure (VHC) to the dentate gyrus (DG) in freely moving rats. Paired pulses of electrical stimulation were delivered to PP or VHC, and evoked field potentials (fEPSPs and pop spikes) were recorded in the DG. Before activating PP or VHC, the TM was triggered by electrical stimulation. Experimentation was performed during four behavioral conditions: exploration, grooming, awake immobility, and slow-wave sleep. Electrical activation of the TM was found to modify dentate fEPSPs evoked by PP or VHC stimulation without generating a field potential by itself. Train stimulation of the TM (100 Hz, 500 ms) preceding paired pulses on the hippocampus by 50 ms decreased dentate fEPSPs in dependence of the ongoing behavior and the pathway stimulated. During exploration but not consummatory behavior, the PP signal was reduced when preceded by TM stimulation; during consummatory behavior but not exploration, the VHC signal was reduced. In contrast to other hippocampal afferents which increase pop spikes but leave fEPSPs unchanged, TM stimulation decreased dentate fEPSPs without affecting pop-spike activity. Thus, the TM-histaminergic system seems to modulate signal processing in the dentate gyrus in a specific way, exerting an inhibitory action on the entorhinal input only during learning-related exploratory behavior.

Task-relevant late positive component in rats: is it related to hippocampal theta rhythm?

Long-latency components of event-related potentials (like the P300 or P3) correlate with the ability of subjects to detect and process unexpected, novel or task-relevant events. Task-relevant late positive components were recorded in the neocortex and hippocampus of rats performing an auditory discrimination task, similar to the "odd-ball" paradigm used in human experiments. Surface and depth electrodes were implanted in anaesthetized rats at frontal, temporal and anterior occipital neocortical regions and the hippocampus. After recovery from surgery rats were trained to discriminate two auditory signals, a frequent irrelevant tone and a rare tone related to water reward. In response to the task-relevant tone but not the irrelevant tone, P300-like late positive components (mean latency of 274 ms) were recorded throughout the surface of the neocortex. The largest amplitudes were found at the anterior occipital cortex situated above the hippocampal CA1 region. The amplitude of the task-relevant positive component increased further with cortical depth without reversing its polarity. An amplitude maximum was found in the CA1 region with a polarity reversal at the pyramidal cell layer and the largest negative amplitude in stratum radiatum. Power spectra of differences between responses evoked by task-relevant tones and those evoked by irrelevant tones revealed peaks in the theta range (4-12 Hz). It is suggested that the P300-like component in rats corresponds to a theta wave out of a burst of hippocampal theta cycles.

Differences of CA3 bursting in DBA/1 and DBA/2 inbred mouse strains with divergent shuttle box performance.

The CA3 bursting activity was compared in slices from two genetically closely related inbred mouse strains with divergent shuttle box performance (low level performing DBA/1 and high performing DBA/2 strains) and a control, behaviorally untested inbred strain, NMRI. Spontaneous population bursts of hippocampal CA3 pyramidal cells (measured extracellularly as field potentials) occurred more frequently in slices of the DBA/2 strain (in 62.5% of the slices in DBA/2 mice) than in the DBA/1 strain (in 33.3% of the slices in DBA/1 mice) and the control NMRI strain (in 33.3% of the slices), whereas the ratio of bursting and nonbursting cells was not different. The resting membrane potential of spontaneously bursting and nonbursting cells was hyperpolarized and the frequency of spontaneous cell bursts were higher in DBA/2 mice compared with both other strains. Slices from the high performing DBA/2 strain had significantly lower thresholds for population bursts evoked by mossy fiber (but not perforant path) stimulation. Electrophysiological properties and bursting patterns of CA3 pyramidal cells are shown to correlate with learning behavior in three different mouse strains. This result is in keeping with an important role of CA3 bursting in memory trace formation.

Current source density analysis of the hippocampal theta rhythm: associated sustained potentials and candidate synaptic generators.

Single-electrode depth profiles of the hippocampal EEG were made in urethane-anesthetized rats and rats trained in an alternating running/drinking task. Current source density (CSD) was computed from the voltage as a function of depth. A problem inherent to AC-coupled profiles was eliminated by incorporating sustained potential components of the EEG. 'AC' profiles force phasic current sinks to alternate with current sources at each lamina, changing the magnitude and even the sign of the computed membrane current. It was possible to include DC potentials in the profiles from anesthetized rats by using glass micropipettes for recording. A method of 'subtracting' profiles of the non-theta EEG from theta profiles was developed as an approach to including sustained potentials in recordings from freely-moving animals implanted with platinum electrodes. 'DC' profiles are superior to 'AC' profiles for analysis of EEG activity because 'DC'-CSD values can be considered correct in sign and more closely represent the actual membrane current magnitudes. Since hippocampal inputs are laminated, CSD analysis leads to straightforward predictions of the afferents involved. Theta-related activity in afferents from entorhinal neurons, hippocampal interneurons and ipsi- and contralateral hippocampal pyramids all appear to contribute to sources and sinks in CA1 and the dentate area. The largest theta-related generator was a sink at the fissure, having both phasic and tonic components. This sink may reflect activity in afferents from the lateral entorhinal cortex. The phase of the dentate mid-molecular sink suggests that medial entorhinal afferents drive the theta-related granule and pyramidal cell firing. The sustained components may be simply due to different average rates of firing during theta rhythm than during non-theta EEG in afferents whose firing rates are also phasically modulated.

Epileptogenic spikes and seizures but not high voltage spindles are induced by local frontal cortical application of gamma-hydroxybutyrate.

Combining the methods of microdialysis and EEG recording, we have examined the effect of unilaterally, intracortically applied gamma-hydroxybutyrate (GHB) on frontal cortical EEG activity in freely moving rats. GHB, a natural endogenous GABA metabolite, is known to induce rhythmic spike and wave activity, resembling generalized petit mal epilepsy. Without GHB, spontaneous high voltage spindles (HVS, 6-9 Hz) were observed during awake and immobile behavior in most of the animals (HVS rats), while others never had any HVS. In those both groups of animals intracortical application of GHB induced epileptogenic spikes (< 0.5 Hz) behaviorally accompanied by occasional myoclonic jerks and epileptic discharges (< 2 Hz) with behavioral convulsions and contraversive movements towards the left hindlimb (seizures) but did not induce HVS or spike and waves, as reported after systemic application. In the group of rats with spontaneous occurring HVS the amplitude of the HVS on the side of the microdialysis probe was suppressed by GHB and GHB-induced spikes invading the contralateral cortex frequently triggered and terminated local HVS. The results point to different neural mechanisms for the generation of HVS and spikes and epileptic discharges (seizures) induced after local intracortical application of GHB.

Somatostatin release in rat neocortex during gamma-hydroxybutyrate-provoked seizures: microdialysis combined with EEG recording.

Gamma-hydroxybutyrate (GHB) was intracortically applied in two doses (first 10 and then 20 mg/ml) to awake Wistar rats using microdialysis. Simultaneously, EEG and the release of somatostatin-like immunoreactivity (SLI) were measured from the frontal cortex. Intracerebrally administered GHB induced cortical epileptogenic spikes, but not high voltage spindles (HVS) as reported after systemic administration, and seizures with myoclonic jerks and contraversive head movements. Compared to the basal level, GHB (10 mg/ml) initially increased the release of SLI (p < 0.05). However, when the frequency of spikes and seizures rose rapidly (p < 0.001), SLI release decreased significantly (p < 0.001). Minimum release of SLI occurred when seizures were most frequent (during perfusion with 20 mg/ml GHB), while after removal of the drug it rose above the basal level (p < 0.05). According to these results, intracortically applied GHB increases the release of SLI in the surrounding tissue. However, further exposure of GHB leads to a manifestation of epileptic spikes and seizures, during which the release of SLI is significantly attenuated. This suggests that release of somatostatin is affected during epileptic phenomena induced also by intracortical GHB application.

Different laminar distribution of flash evoked potentials in cortical areas 17 and 18 b of freely moving rats.

The laminar distribution of flash evoked field potential (VEP) was investigated in the visual cortical areas 17 and 18 b in freely moving rats. Averaged VEPs were recorded during stable relaxed wakefulness characterized behaviorally and polygraphically. The depth profiles of the main VEP components displayed polarity reversals in lamina V in every electrode track through area 17 while no polarity reversal was observed in any track through area 18 b. The primary negative component (N30) had an amplitude maximum in lamina IV in both areas. Current source-density analysis (CSD) in connection with amplitude depth profiles indicated that the surface-negative component N30 is generated mainly by the synaptic excitatory inputs in lamina IV. The negative peak of the flash-evoked afterdischarges in area 17 are generated the same way. The data imply a more concentrated field generator in area 17 with densely packed cellular elements responding synchronously to the flash. In area 18 b, either the anatomical distribution or the temporal relationship of the responding elements seems to be different.

Permanent changes of the visually evoked responses in the superior colliculus after early postnatal treatment with monosodium-L-glutamate.

10 rats of the Long-Evans strain were treated from the first to the eleventh postnatal day (pd) with daily subcutaneous injections of 4 mg/g body weight monosodium-L-glutamate (MSG) in aqua dest. 10 rats were used as controls and received isotonic NaCl-solution on the same days. When rats were 4 months old, electrodes were implanted in different depths of the superior colliculus (CS) to investigate averaged evoked potentials by flash (VEP) and by click stimuli (AEP). The VEP in the superficial layers of the CS of MSG rats were strongly reduced in their amplitudes and irregularly shaped with the most prominent result that the primary negative component N28 was missing. The deeper recordings were made, the less this polarity-reversed primary component was affected with still significant amplitude reduction in the deepest layer. Shape and peak times of the AEP from the same electrodes in different depths were not significantly changed. However, the amplitudes of the early negative-positive and the second negative-positive deflections were enhanced in all MSG treated rats, and the amplitude proportions between VEP and AEP were in favour of AEP, in contrast to the controls. Heteromodal interactions of paired click and flash with an interval of 100 ms resulted in nearly total suppression of the VEP, in contrast to controls in which VEP were rather uninfluenced by the preceding click. Also the behaviour-dependent reduction of VEP during grooming and exploratory behaviour was much stronger in MSG treated rats compared with controls. The evoked potential analyses revealed greater interindividual heterogeneity of VEP in MSG treated rats than in controls.

Visually evoked responses in the primary cortex of rats are permanently changed by early postnatal treatment with monosodium-L-glutamate.

13 rats of the Long-Evans strain were treated from the first to the eleventh postnatal day (pd) with daily subcutaneous injections of 4 mg/g body weight monosodium-L-glutamate (MSG) in aqua dest. Further 13 rats were used as controls and received isotonic NaCl-solution on the same days. When rats were four months old, epidural electrodes were implanted on the visual cortex to investigate averaged evoked potential by flash (VEP) and by click stimuli (AEP). All VEP components of MSG rats were changed in their amplitudes and peak times. Mainly the early components were strongly reduced and irregularly split. AEP in the visual cortex of MSG rats were also significantly changed. Photically evoked afterdischarges (AD) were not statistically altered. The evoked potential analysis revealed great interindividual heterogeneity and their topographical distribution was also strongly modified. The postmortem macroscopic inspection of the brains resulted in strong atrophy of the optic nerves and the chiasma. During two-month observations we observed no restoration of the evoked potentials to normal values.

Sensory interaction in the superior colliculus of freely moving rat indicated by evoked potentials.

Sensory monomodal and bimodal interaction was compared in the anterior medial superior colliculus (CS) of freely moving Long-Evans rats with chronically implanted electrodes using pairs of click and flash stimuli separated by intervals of 100 ms. The amplitudes and peak times of first and second evoked potentials were statistically evaluated and compared with the uninfluenced control values of visually and acoustically evoked potentials (VEP and AEP) on the back-ground of relatively constant relaxed wakefulness. Heteromodal interactions were characterized by only very small and in most cases insignificant changes, compared with very striking depressions of component amplitudes of the second EP in monomodal paired stimulation. Significant differences of AEP and VEP amplitude and peak time changes in superficial and in deep layers of the CS indicated that the sensory interaction is different, corresponding to the functional structure of CS layers. The amplitude of the second negativity N32 in AEP 100 ms after flash is significantly influenced in the superficial layers, but not in the deeper ones. The VEP peak times are prolonged after click only in the deeper layers.

Long-term effects on behaviour after postnatal treatment with monosodium-L-glutamate.

22 rats of the Long-Evans strain (11 males and 11 females) were treated from the first to the eleventh postnatal day (pd) with daily subcutaneous injections of 4 mg/g body weight monosodium-L-glutamate (MSG) in aqua dest. Further 11 males and 7 females were used as controls and received isotonic NaCl-solution on the same days. The neurological investigation after 1 month revealed no difference between MSG-treated or untreated controls. All MSG treated rats were retarded in growth and body weight development. None of them died from the treatment. During 10 min exposure in a 60 x 75 x 22 cm open field (OF) we found higher rates of infrared beam crossing on pd 12-14, more rearing on pd 12, 16 and 32 and less immobility of MSG rats. Latencies of immobility and grooming were significantly prolonged versus controls. We found no essential differences of MSG effects between males and females. At the age of 4 months the ability for active avoidance was tested. When they could find the escape possibility, then the escape velocity was like in controls. But MSG rats had troubles to find this possibility at the beginning of a Y-maze training and during alternation of the goal (brightness discrimination). They never found the escape and avoidance possibility in a vertical jump test.

Behaviour-dependent variability of potentials in the somatosensory cortex evoked by stimulation of the trigeminal nuclei in freely moving rats.

Nine hooded rats with chronically implanted epidural recording electrodes on the right primary somatosensory cortex, the olfactory bulb and bipolar stimulating electrodes in the left ponto-mesencephalic trigeminal nuclei and parabrachial region were investigated during different patterns of spontaneous behaviour. The early positive-negative component of the TNEP with peak times P5 and NII (ms) appeared about 1 ms earlier than after tooth pulp stimulation. The amplitude P5-N11 was slightly increased during drowsiness, decreased during slow wave sleep and was strongly decreased in behavioural patterns with movements, always compared with relaxed wakefulness. The behaviour-dependent changes of cortical EP to stimulation of trigeminal nuclei (TNEP) were analogous to those after tooth pulp stimulation.

Hippocampal responses evoked by tooth pulp and acoustic stimulation: depth profiles and effect of behavior.

Averaged evoked potentials and unitary discharges in response to tooth pulp and acoustic click stimuli were recorded from the hippocampus of freely moving rats. The spatial distribution of evoked field responses to tooth pulp stimulation and acoustic clicks were identical. Averaged evoked potentials consisted of a large negative deflection (N1) preceded by a small positive potential (P1). The shortest latency N1 in response to tooth pulp stimulation was recorded from the middle third of the dentate molecular layer and the outer portion of apical dendrites of CA3 (27 ms). The peak latency of N1 was significantly longer (34 ms) in the stratum radiatum of CA1. Laminar profiles of N1 in the dentate gyrus and CA3 were similar to that evoked by electrical stimulation of the medial entorhinal afferents; in CA1 the depth profiles of the potentials were similar to the response profile evoked by the Schaffer collaterals. Largest amplitude P1 was obtained from above the pyramidal layer of CA1 and the hilus. Both sensory modalities were able to modify the discharge rate of neurons in all hippocampal regions. The amplitude of evoked field potentials and cellular responses were dependent upon both the ongoing behavior of the animal and the nature of its response to the stimulus. The largest amplitude evoked potentials were recorded during immobility and slow wave sleep. On the other hand, virtually no potentials were obtained during exploratory behaviors associated with theta EEG activity. The findings indicate that information about sensory stimuli can reach the hippocampus by two distinctive pathways: a short latency inhibitory input via the fimbria-fornix and a longer latency path via the entorhinal cortex. It is suggested that neuronal mechanisms involved in theta EEG block the sequential activation of the unidirectional entorhinal-hippocampal circuitry.

Tooth pulp evoked potentials in trigeminal nuclei and parabrachial region of the freely moving rat.

Twelve hooded rats with chronically implanted recording electrodes in the left ponto-mesencephalic trigeminal nuclei and parabrachial region and bipolar stimulating electrodes in the left upper incisor were investigated in different states of spontaneous behaviour. At all recording sites tooth pulp evoked potentials (TPEP) with the following main components were recorded: a small negative component with a peak time of N 2 ms, followed by a second negativity with the peak time of N 6 ms and a slow large positive-negative component with the peak time of N 28 ms. The corresponding positive peaks were: P 3 ms, P 13 ms, P 58 ms. In all rats we observed a great variability of TPEP components in different waking states. A maximal decrease of TPEPs was observed during strong grooming compared with relaxed wakefulness.

Tooth pulp evoked potential in the thalamus of freely moving rats.

Eleven hooded rats with bipolar stimulating electrodes in the left upper incisor and recording electrodes in the ventral posteromedial (VPM), ventral dorsomedial (VDM) and paracentral (NPC) nuclei of the contralateral thalamus and the somatosensory cortex (SC) were investigated in different states of spontaneous behaviour. The early complex of the thalamic averaged tooth pulp evoked potentials (TPEP) consisted of two negative-positive waves, a small (N2, P4) and a larger one (N6, P14). Later components appeared with different peak times and amplitudes depending on the localization of the recording electrode. The single components of the thalamic TPEP decreased differently during behavioural activation between 20 and 80% with maximal expression during intensive grooming.

[Variability of cortical evoked potentials in response to tooth pulp stimulation in the freely moving rat]. / Izmenchivost' kortikal'nykh vyzvannykh potentsialov pri razdrazhenii pul'py zuba u krys v usloviiakh svobodnogo povedeniia.

Evoked potentials (EP) due to the stimulation of the upper incisor tooth pulp were recorded from the somatosensory cortex of the freely moving adult rats. Background EEG, motor activity of an animal and respiratory potentials of the olfactory bulb were recorded simultaneously. EP configurations and mean amplitudes of primary complex (P1 + N1) differed significantly during states of sleep, drowsiness, relaxed wakefulness, grooming and exploratory behaviour; primary complex amplitude during intensive motor activities was several times less than during periods without movements. Negative correlation of the EP amplitude and instant respiration rate was found during relaxed wakefulness: it was less pronounced during periods with motor activities. At the same time direct parallelism between changes in EP and respiration rate was absent: the EP depression was maximal during grooming, while the respiration rate was minimal during exploratory behaviour.

Behaviour-dependent changes of visually evoked potential components in the superior colliculus of freely moving rats.

Amplitudes and peak times of visually evoked potential (VEP) components in superficial and deeper layers of the superior colliculus of 24 rats were measured during slow wave sleep (S), relaxed wakefulness (RW), grooming (G) and exploratory behaviour (E). All peaks occurred later during S than during RW, whereas only a few peak times were significantly longer in activated states compared with RW. Positive and negative peaks between 35 and 60 ms were significantly (p less than 0.01) prolonged during G and E. Corresponding peaks of the polarity reversed VEP appear 1-4 ms later than in the superficial VEP when compared in identical behavioural states. Significant amplitude decrease (p less than 0.01) of almost all components related to RW was found in G and E and of components N-39-P51 and N60-P71 in S. These changes were relatively different for each component and each behavioural state. The amplitude changes of the polarity reversed VEP were similar but not identical (as a mirror image) with superficial VEP. The different behaviour-dependent patterns of the VEP components indicate different interactions in the neuron pools of superior colliculus.

Intensity-dependent changes of visually evoked potential components in the superior colliculus of freely moving rats.

Amplitudes and peak times of averaged visually evoked potentials (VEP) recorded in the superficial layers of the anterior medial superior colliculus were measured in 7 freely moving rats. The amplitudes of P21-N29 decreased significantly to 47% (p = 0.01), the amplitudes of components N41-P54 and P54-N64 to 29 and 32% (p = 0.01) when the flash intensity was lowered six times, whereas components N29-P36 and P74-N85 showed no significant decrease. During exploratory behaviour all the components were significantly lower than during relaxed wakefulness, except N29-P36 and P74-N85. The course of their intensity-dependent decrease was different. Peak times of both early negative components N29 and N41 increased exponentially with decreasing flash intensity during relaxed wakefulness. The peak times of later negative components N64 and N85 increased only with the lowest intensity. During exploratory behaviour peak time changes were evidently smaller. The data suggest that the different changes of components reflect the activity of different neuron types.

Correlation between peak times of visually evoked potentials and an amplitude coefficient of acoustically evoked potentials in the superior colliculus on the freely moving rat.

Components of VEP and AEP of 27 male hooded rats with chronically implanted electrodes in the anterior medial superior colliculus (CS) were measured and compared during relaxed wakefulness. Peak times of the VEP are correlated to the log of the quotient II/I of amplitudes P20-N32 (II) and P5-N10 (I) of AEP on the same recording point. The conclusion is drawn that the configuration of the collicular EP strongly depends on the distribution of neuronal elements around the electrode tip.