Hippocampal memory consolidation during sleep: a comparison of mammals and birds

The transition from wakefulness to sleep is marked by pronounced changes in brain activity. The brain rhythms that characterize the two main types of mammalian sleep, slow‐wave sleep (SWS) and rapid eye movement (REM) sleep, are thought to be involved in the functions of sleep. In particular, recent theories suggest that the synchronous slow‐oscillation of neocortical neuronal membrane potentials, the defining feature of SWS, is involved in processing information acquired during wakefulness. According to the Standard Model of memory consolidation, during wakefulness the hippocampus receives input from neocortical regions involved in the initial encoding of an experience and binds this information into a coherent memory trace that is then transferred to the neocortex during SWS where it is stored and integrated within preexisting memory traces. Evidence suggests that this process selectively involves direct connections from the hippocampus to the prefrontal cortex (PFC), a multimodal, high‐order association region implicated in coordinating the storage and recall of remote memories in the neocortex. The slow‐oscillation is thought to orchestrate the transfer of information from the hippocampus by temporally coupling hippocampal sharp‐wave/ripples (SWRs) and thalamocortical spindles. SWRs are synchronous bursts of hippocampal activity, during which waking neuronal firing patterns are reactivated in the hippocampus and neocortex in a coordinated manner. Thalamocortical spindles are brief 7–14 Hz oscillations that may facilitate the encoding of information reactivated during SWRs. By temporally coupling the readout of information from the hippocampus with conditions conducive to encoding in the neocortex, the slow‐oscillation is thought to mediate the transfer of information from the hippocampus to the neocortex. Although several lines of evidence are consistent with this function for mammalian SWS, it is unclear whether SWS serves a similar function in birds, the only taxonomic group other than mammals to exhibit SWS and REM sleep. Based on our review of research on avian sleep, neuroanatomy, and memory, although involved in some forms of memory consolidation, avian sleep does not appear to be involved in transferring hippocampal memories to other brain regions. Despite exhibiting the slow‐oscillation, SWRs and spindles have not been found in birds. Moreover, although birds independently evolved a brain region—the caudolateral nidopallium (NCL)—involved in performing high‐order cognitive functions similar to those performed by the PFC, direct connections between the NCL and hippocampus have not been found in birds, and evidence for the transfer of information from the hippocampus to the NCL or other extra‐hippocampal regions is lacking. Although based on the absence of evidence for various traits, collectively, these findings suggest that unlike mammalian SWS, avian SWS may not be involved in transferring memories from the hippocampus. Furthermore, it suggests that the slow‐oscillation, the defining feature of mammalian and avian SWS, may serve a more general function independent of that related to coordinating the transfer of information from the hippocampus to the PFC in mammals. Given that SWS is homeostatically regulated (a process intimately related to the slow‐oscillation) in mammals and birds, functional hypotheses linked to this process may apply to both taxonomic groups.     

Gene expression in the rodent brain is associated with its regional connectivity

The putative link between gene expression of brain regions and their neural connectivity patterns is a fundamental question in neuroscience. Here this question is addressed in the first large scale study of a prototypical mammalian rodent brain, using a combination of rat brain regional connectivity data with gene expression of the mouse brain. Remarkably, even though this study uses data from two different rodent species (due to the data limitations), we still find that the connectivity of the majority of brain regions is highly predictable from their gene expression levels-the outgoing (incoming) connectivity is successfully predicted for 73% (56%) of brain regions, with an overall fairly marked accuracy level of 0.79 (0.83). Many genes are found to play a part in predicting both the incoming and outgoing connectivity (241 out of the 500 top selected genes, p-value<1e-5). Reassuringly, the genes previously known from the literature to be involved in axon guidance do carry significant information about regional brain connectivity. Surveying the genes known to be associated with the pathogenesis of several brain disorders, we find that those associated with schizophrenia, autism and attention deficit disorder are the most highly enriched in the connectivity-related genes identified here. Finally, we find that the profile of functional annotation groups that are associated with regional connectivity in the rodent is significantly correlated with the annotation profile of genes previously found to determine neural connectivity in C. elegans (Pearson correlation of 0.24, p<1e-6 for the outgoing connections and 0.27, p<1e-5 for the incoming). Overall, the association between connectivity and gene expression in a specific extant rodent species' brain is likely to be even stronger than found here, given the limitations of current data.     

The functional status of the Helicobacter pylori sabB adhesin gene as a putative marker for disease outcome

Background. Helicobacter pylori factors that contribute to disease outcome are largely unknown, but intimate contact with host cells mediated by outer membrane proteins is thought to play an important role. Expression of the outer membrane proteins OipA, HopZ, SabA, and SabB is regulated by phase‐variable dinucleotide repeats in the coding regions of the respective genes. We have evaluated the correlation between the expression status of these four genes and disease outcome of H. pylori infection in a Dutch patient population. Materials and Methods. H. pylori strains, isolated from 96 Dutch patients with gastritis (n = 29), duodenal ulcer (n = 28), gastric ulcer (n = 21), gastric carcinoma (n = 9), and lymphoma (n = 9), were analyzed for the ‘on/off’ expression status of the H. pylori genes oipA, hopZ, sabA, and sabB by direct DNA sequence analysis of amplified fragments. Results. The off‐status of sabB was significantly associated with duodenal ulcer (p = .036), but not with gastric ulcer. In contrast, the expression status of oipA, hopZ, and sabA did not correlate with disease outcome. Furthermore, lymphoma strains appeared to express a significantly smaller amount of putative adhesins when compared to gastritis, gastric ulcer, duodenal ulcer and gastric carcinoma strains (p < .02 for all groups tested). Conclusion. The off‐status of sabB was found to be associated with duodenal ulcer disease, and thus represents a putative marker for disease outcome. Assuming that SabB is involved in bacterial adhesion, this association suggests that adherent H. pylori are more prone to elimination by the host immune system.     

Molecular Cloning and Differential Expression Patterns of Avian Glutamate Receptor mRNAs

Abstract: We have identified and studied potential ionotropic glutamate receptor genes in pigeon brain. Three cDNA clones exhibit significant amino acid sequence identity to members of a rodent ligand-gated ion channel family. One of them, GluP-II, encodes a full-length AMPA-sensitive glutamate receptor GluR2 (GluR-B) homologue, whereas the other two partial clones, designated as GluP-III and -IV, are nearly identical to rodent GluR3 (GluR-C) and GluR4 (GluR-D) receptor subunits. Northern analysis demonstrated that the avian genes are widely expressed in the brain. Within the brain regions analyzed by in situ hybridization histochemistry, the three avian GluR subunits showed distinct and regionally specific mRNA expression patterns in the adult. Most of the differences in their expression were observed in cell types of the telencephalon, certain thalamic nuclei, the optic tectum, and the cerebellar cortex. A particularly striking finding was the expression of GluP-II in Golgi epithelial/Bergmann glial cells. In contrast, Bergmann glial cells in rat cerebellum do not express GluR2 (GluR-B) subunit genes. Immunoreactivity for a monoclonal sequence-specific antipeptide antibody was widespread and most prominent in Purkinje cell perikarya and their dendrites, neuronal cell bodies of the ectostriatum, and the deep optic tectum. These results demonstrate the existence of multiple subunits of the ionotropic glutamate receptor channel family in avians. Excitatory amino acid receptor genes appear to be highly conserved during evolution.     

The effect of propranolol on cAMP concentration in the rat preoptic region during the wake-sleep cycle

In control conditions preoptic cAMP concentration during wakefulness was significantly higher than during synchronized sleep. No differences in nucleotide concentration were observed in the cerebral cortex. Propranolol decreases brain cAMP concentration. This change was associated with the suppression of the difference observed between wakefulness and synchronized sleep in the preoptic region.     

A novel role for calcium/calmodulin kinase II within the brainstem pedunculopontine tegmentum for the regulation of wakefulness and rapid eye movement sleep

Considerable evidence suggests that the brainstem pedunculopontine tegmentum (PPT) neurons are critically involved in the regulation of rapid eye movement (REM) sleep and wakefulness (W); however, the molecular mechanisms operating within the PPT to regulate these two behavioral states remain relatively unknown. Here we demonstrate that the levels of calcium/calmodulin kinase II (CaMKII) and phosphorylated CaMKII expression in the PPT decreased and increased with 'low W with high REM sleep' and 'high W/low REM sleep' periods, respectively. These state-specific expression changes were not observed in the cortex, or in the immediately adjacent medial pontine reticular formation. Next, we demonstrate that CaMKII activity in the PPT is negatively and positively correlated with the 'low W with high REM sleep' and 'high W/low REM sleep' periods, respectively. These differences in correlations were not seen in the medial pontine reticular formation CaMKII activity. Finally, we demonstrate that with increased PPT CaMKII activity observed during high W/low REM sleep, there were marked shifts in the expression of genes that are involved in components of various signal transduction pathways. Collectively, these results for the first time suggest that the increased CaMKII activity within PPT neurons is associated with increased W at the expense of REM sleep, and this process is accomplished through the activation of a specific gene expression profile.     

Auditory processing across the sleep-wake cycle: simultaneous EEG and fMRI monitoring in humans

We combined fMRI and EEG recording to study the neurophysiological responses associated with auditory stimulation across the sleep-wake cycle. We found that presentation of auditory stimuli produces bilateral activation in auditory cortex, thalamus, and caudate during both wakefulness and nonrapid eye movement (NREM) sleep. However, the left parietal and, bilaterally, the prefrontal and cingulate cortices and the thalamus were less activated during NREM sleep compared to wakefulness. These areas may play a role in the further processing of sensory information required to achieve conscious perception during wakefulness. Finally, during NREM sleep, the left amygdala and the left prefrontal cortex were more activated by stimuli having special affective significance than by neutral stimuli. These data suggests that the sleeping brain can process auditory stimuli and detect meaningful events.