SummaryThe mammalian radiation has corresponded with rapid changes in noncoding regions of the genome, but we lack a comprehensive understanding of regulatory evolution in mammals. Here, we track the evolution of promoters and enhancers active in liver across 20 mammalian species from six diverse orders by profiling genomic enrichment of H3K27 acetylation and H3K4 trimethylation. We report that rapid evolution of enhancers is a universal feature of mammalian genomes. Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements. In contrast, almost all liver promoters are partially or fully conserved across these species. Our data further reveal that recently evolved enhancers can be associated with genes under positive selection, demonstrating the power of this approach for annotating regulatory adaptations in genomic sequences. These results provide important insight into the functional genetics underpinning mammalian regulatory evolution.
This review charts recent advances from a variety of disciplines that create a new perspective on why the multiple hippocampal–anterior thalamic interconnections are together vital for human episodic memory and rodent event memory. Evidence has emerged for the existence of a series of parallel temporal–diencephalic pathways that function in a reciprocal manner, both directly and indirectly, between the hippocampal formation and the anterior thalamic nuclei. These extended pathways also involve the mammillary bodies, the retrosplenial cortex and parts of the prefrontal cortex. Recent neuropsychological findings reveal the disproportionate importance of these hippocampal–anterior thalamic systems for recollective rather than familiarity-based recognition, while anatomical studies highlight the precise manner in which information streams are kept separate but can also converge at key points within these pathways. These latter findings are developed further by electrophysiological stimulation studies showing how the properties of the direct hippocampal–anterior thalamic projections are often opposed by the indirect hippocampal projections via the mammillary bodies to the thalamus. Just as these hippocampal–anterior thalamic interactions reflect an interdependent system, so it is also the case that pathology in one of the component sites within this system can induce dysfunctional changes to distal sites both directly and indirectly across the system. Such distal effects challenge more traditional views of neuropathology as they reveal how extensive covert pathology might accompany localised overt pathology, and so impair memory.
The anterior thalamic nuclei (ATN), a central component of Papez' circuit, are generally assumed to be key constituents of the neural circuits responsible for certain categories of learning and memory. Supporting evidence for this contention is that damage to either of two brain regions, the medial temporal lobe and the medial diencephalon, is most consistently associated with anterograde amnesia. Within these respective regions, the hippocampal formation and the ATN (anteromedial, anteroventral, and anterodorsal) are the particular structures of interest. The extensive direct and indirect hippocampal-anterior thalamic interconnections and the presence of theta-modulated cells in both sites further support the hypothesis that these structures constitute a neuronal network crucial for memory and cognition. The major tool in understanding how the brain processes information is the analysis of neuronal output at each hierarchical level along the pathway of signal propagation coupled with neuroanatomical studies. Here, we discuss the electrophysiological properties of cells in the ATN with an emphasis on their role in spatial navigation. In addition, we describe neuroanatomical and functional relationships between the ATN and hippocampal formation.
We compared neuronal activation, as measured by Fos staining, during different spatial tasks in two experiments. The counts of Fos-stained neurons in the hippocampus increased as the spatial demands of the tasks increased, the tasks having been carefully matched for other factors. In Experiment 1, matched groups of rats either ran a standard eight-arm radial maze task or were trained to run up and down just one arm of the maze; the number of runs and rewards was identical in both conditions. In Experiment 2, rats were trained on the eight-arm maze but in different rooms. On the critical test day, both groups were run in the same room so that one group now performed with novel landmarks. All hippocampal subfields (dentate gyrus, CA3, CA1, dorsal, ventral, and caudal subiculum) showed a relative increases in c-fos activation in the eight-arm (Experiment 1) and novel room (Experiment 2) conditions, the sole exception being the ventral subiculum in Experiment 2. Although increased c-fos activation was found in both dorsal and ventral hippocampus, in Experiment 2 the relative increase was significantly greater in the dorsal hippocampus. Parahippocampal cortices responded heterogeneously: the perirhinal cortex failed to show increased activation in both experiments, in contrast to the entorhinal and postrhinal cortices. Subsequent comparisons confirmed that the perirhinal and postrhinal cortices responded in qualitatively different ways, the perirhinal cortex differing from the rest of the hippocampal formation. These experiments, which provide the first analysis of hippocampal Fos production during tests of allocentric spatial working memory, reveal that all components of the hippocampus are activated, but that under certain conditions the dorsal hippocampus is disproportionately involved.
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