Somatostatinergic modulation of firing pattern and calcium-activated potassium currents in medium spiny neostriatal neurons.

Somatostatin is synthesized and released by aspiny GABAergic interneurons of the neostriatum, some of them identified as low threshold spike generating neurons (LTS-interneurons). These neurons make synaptic contacts with spiny neostriatal projection neurons. However, very few somatostatin actions on projection neurons have been described. The present work reports that somatostatin modulates the Ca(2+) activated K(+) currents (K(Ca) currents) expressed by projection cells. These actions contribute in designing the firing pattern of the spiny projection neuron; which is the output of the neostriatum. Small conductance (SK) and large conductance (BK) K(Ca) currents represent between 30% and 50% of the sustained outward current in spiny cells. Somatostatin reduces SK-type K(+) currents and at the same time enhances BK-type K(+) currents. This dual effect enhances the fast component of the after hyperpolarizing potential while reducing the slow component. Somatostatin then modifies the firing pattern of spiny neurons which changed from a tonic regular pattern to an interrupted "stuttering"-like pattern. Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) tissue expression analysis of dorsal striatal somatostatinergic receptors (SSTR) mRNA revealed that all five SSTR mRNAs are present. However, single cell RT-PCR profiling suggests that the most probable receptor in charge of this modulation is the SSTR2 receptor. Interestingly, aspiny interneurons may exhibit a "stuttering"-like firing pattern. Therefore, somatostatin actions appear to be the entrainment of projection neurons to the rhythms generated by some interneurons. Somatostatin is then capable of modifying the processing and output of the neostriatum.

Rapid eye movement sleep dreaming is characterized by uncoupled EEG activity between frontal and perceptual cortical regions.

EEG coherent activity is involved in the binding of spatially separated but temporally correlated stimuli into whole events. Cognitive features of rapid eye movement sleep (REM) dreaming resemble frontal lobe dysfunction. Therefore, temporal coupling of EEG activity between frontal and perceptual regions was analyzed from 10 min prior to dream reports (8 adults) from stage-2 and REM sleep. EEG correlation between frontal and perceptual regions decreased and, among perceptual regions increased during REM. The temporal dissociation of EEG activity between executive and perceptual regions supplies an inadequate mechanism for the binding and interpretation of ongoing perceptual activity resulting in dream bizarreness.

EEG bands during wakefulness, slow-wave, and paradoxical sleep as a result of principal component analysis in the rat.

Rat EEG has been empirically divided in bands that frequently do not correspond with EEG generators nor with the functional meaning of EEG rhythms. Power spectra from wakefulness (W), slow-wave sleep (SWS), and paradoxical sleep (PS) of Wistar rats were submitted to Principal Component Analyses (PCA) to investigate which frequencies are covariant. Three independent eigenvectors were identified for SWS: a band between 1-6, an intermediate band between 7-15, and a fast band between 16-32 Hz (90.74% of the variance); two independent eigenvectors were extracted for PS: slow frequencies between 1-6 covarying together with frequencies between 11-16 Hz, and activity between 6-10 covarying together with fast frequencies between 17-32 Hz (80.38% of the variance); four eigen-vectors were obtained for W: 3-7, 8-9, 10-21 and 21-32 Hz (81.47% of the variance). Vigilance states showed significant differences in AP from 1 to 22 Hz. PCA extracted broad bands different for each vigilance state, which included the most representative EEG activities characteristic of them. These results indicate that during SWS, slow oscillations include frequencies up to 6 Hz, and spindle oscillations frequencies down to 7 Hz. No alpha frequencies were identified as an independent band. Frequencies within theta and beta were gathered in the same eigenvector during PS and in different eigenvectors during W suggesting coordinated activation of hippocampal and cortical systems during PS. These bands are consistent with the underlying neurophysiological mechanisms of sleep and wakefulness and with firing frequencies of generators of rhythmic activity obtained in cellular studies in animals.

Paradoxical sleep is characterized by uncoupled gamma activity between frontal and perceptual cortical regions.

STUDY OBJECTIVES: Coherent activity of fast activity has been postulated to be a common language of the brain involved in the processing of information and in integration of spatially separated but temporally correlated stimuli into whole events. Any disruption affecting temporality would result in distortion of cognitive activity. Dreaming during paradoxical sleep (PS) shows cognitive alterations that mimic frontal lobe dysfunction. Decreased temporal coupling of EEG between frontal and perceptual regions was hypothesized. The main objective was to explore temporal relationships of fast activity among these regions. DESIGN: N/A. SETTING: N/A. PARTICIPANTS: 8 young adults. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Interhemispheric (INTERr) and intrahemispheric (INTRAr) EEG correlation spectra (1-50 Hz) were obtained for wakefulness, stage 2, stage 4, and PS during the second night spent at the laboratory. INTERr showed a significant overall increase during sleep in comparison to wakefulness, whereas INTRAr of fast activity (27-48 Hz) between frontal-perceptual regions (F-P, F-O, F-T, Fp-P, Fp-T) decreased exclusively during PS while INTRAr among perceptual regions (P-O, P-T, O-T) maintained wakefulness values. CONCLUSIONS: Present results demonstrate state- and frequency-dependent shifts on temporal coupling. The hypothesized decrease in correlation of fast activity between frontal and perceptual regions during PS was confirmed. This decrease of temporal coupling might underlie the loss of voluntary direction of thinking and congruence with social and temporal context and the lack of judgment and passive acceptance of bizarreness during PS dreaming. The wakefulness levels in correlation of fast activity among perceptual regions might explain perceptual acuity during PS dreaming.

A new human tumor-associated antigen (TLP) is naturally expressed in rat DHD-K12 colorectal tumor cells.

Renewed interest in cancer immunotherapy has been raised by the availability of a variety of tumor-associated antigens and animal models. We have recently described the presence of a new antigen, TLP, in sera and cancer tissue from lung and colorectal cancer patients. In order to develop an experimental model suitable for preclinical studies on cancer vaccines, we investigated the presence of TLP antigen in vitro, in the DHD-K12 cell line and in vivo, in metastases induced in syngeneic BDIX rats by DHD-K12 cell injection. TLP was not detected in any tissue of healthy rats nor in normal tissues of tumor-bearing rats. This is in agreement with our previous studies, in which we had demonstrated that TLP is expressed in human colorectal cancer and adenomas but not in normal colonic mucosa. Our results indicate TLP as a possible human tumor-specific antigen naturally expressed in DHD-K12 tumor syngeneic to immunocompetent BDIX rats.

D2 dopamine receptors in striatal medium spiny neurons reduce L-type Ca2+ currents and excitability via a novel PLC[beta]1-IP3-calcineurin-signaling cascade.

In spite of the recognition that striatal D(2) receptors are critical determinants in a variety of psychomotor disorders, the cellular mechanisms by which these receptors shape neuronal activity have remained a mystery. The studies presented here reveal that D(2) receptor stimulation in enkephalin-expressing medium spiny neurons suppresses transmembrane Ca(2+) currents through L-type Ca(2+) channels, resulting in diminished excitability. This modulation is mediated by G(beta)(gamma) activation of phospholipase C, mobilization of intracellular Ca(2+) stores, and activation of the calcium-dependent phosphatase calcineurin. In addition to providing a unifying mechanism to explain the apparently divergent effects of D(2) receptors in striatal medium spiny neurons, this novel signaling linkage provides a foundation for understanding how this pivotal receptor shapes striatal excitability and gene expression.

Amplitude reduction in visual event-related potentials as a function of sleep deprivation.

Eight adult males were subjected to 40 hours of total sleep deprivation (TSD). Reaction time in a visual task and electroncephalographam (C3) were evaluated every 2 hours. One second of EEG before the stimuli was Fourier-transformed, and 750 ms after target and nontarget stimuli were averaged and visual event-related potentials (ERP) were obtained. Factorial analysis identified time windows that showed significant amplitude reduction and longer latencies with TSD: (1) 140 to 288 ms (P180-N242-P281); (2) 288 to 413 ms and 601 to 749 ms (N382; P718) and; (3) 531 to 601 ms (N500). Effect was strongest for N382 and P718, the amplitudes of which dropped to 20% of original size. The entire waveform recovered initial amplitudes and latencies after recovery sleep except for P718 latency. Waveforms within similar time intervals have been associated with attentional gating, sensory discrimination, target selection, uncertainty and decision processes. Amplitudes of the visual ERP were inversely correlated with hours of TSD, reaction time, and absolute power of the prestimulus EEG. Present results clearly show changes in fundamental neurophysiologic mechanisms as a result of TSD, indicating variability and reduction of the alertness mechanisms and changes in thalamocortical gating affecting attention, discrimination and decision-making.

Correlation between induction of lymphocyte apoptosis and prostaglandin E2 production by macrophages infected with HIV.

Several data indicate that HIV infection of antigen-presenting cells (APCs) and apoptosis of lymphocytes play important roles in pathogenesis of AIDS. We have recently demonstrated that prostaglandin E2 (PGE2) can cause thymocyte apoptosis in vivo. In the present study we have investigated the possibility that the intercellular contacts between HIV-infected APCs and lymphocytes could induce apoptosis in the latter population and that PGE2-production by HIV-infected APCs could be involved in the hypothesized phenomenon. Monocytes/macrophages separated from peripheral blood mononuclear cells (PBM phi) of healthy donors were infected in vitro and maintained in culture. PGE2 was promptly produced by HIV-infected PBM phi and values of PGE2 concentrations in supernatants over the background noninfected controls persisted for more than 2 weeks. HIV-infected PBM phi or cell-free supernatants from their cultures were then added to autologous uninfected lymphocytes and apoptosis was assessed by morphological criteria and by looking to the expression of tissue transglutaminase, one of the effector elements of the program of cell death. In both culture conditions the percentage of apoptotic lymphocytes was significantly increased in respect to values obtained in control cultures. When a cyclooxygenase inhibitor was added to the HIV-infected PBM phi cultures, the percentage of apoptotic lymphocytes was reduced at levels similar to those observed after cocultivation with uninfected PBM phi or exposure to supernatants from uninfected PBM phi. In addition, a substantial increase in apoptosis in lymphocytes from healthy donors was found following PGE2 treatment in vitro.