Comparative organization of the claustrum: what does structure tell us about function?

The claustrum is a subcortical nucleus present in all placental mammals. Many anatomical studies have shown that its inputs are predominantly from the cerebral cortex and its outputs are back to the cortex. This connectivity thus suggests that the claustrum serves to amplify or facilitate information processing in the cerebral cortex. The size and the complexity of the cerebral cortex change dramatically over evolution. Rodents are lissencephalic, with few cortical areas, while many primates have a greatly expanded cortex and many cortical areas. This evolutionary diversity in the cerebral cortex raises several questions about the claustrum. Does its volume expand in coordination with the expansion of cortex and does it acquire new functions related to the new cortical functions? We have examined the organization of the claustrum in animals with large brains, including great apes and cetaceans. Our data suggest that the claustrum is not always a continuous structure. In monkeys and gorillas there are a few isolated islands of cells near the main body of the nucleus. In cetaceans, however, there are many isolated cell islands. These data suggest constraints on the possible function of the claustrum. Some authors propose that the claustrum has a more global role in perception or consciousness that requires intraclaustral integration of information. These theories postulate mechanisms like gap junctions between claustral cells or a syncytium to mediate intraclaustral processing. The presence of discontinuities in the structure of the claustrum, present but minimal in primates, but dramatically clear in cetaceans, argues against the proposed mechanisms of intraclaustral processing of information. The best interpretation of function, then, is that each functional subdivision of the claustrum simply contributes to the function of its cortical partner

The transcription factor Nfix is essential for normal brain development

Background: The Nuclear Factor I (NFI) multi-gene family encodes site-specific transcription factors essential for the development of a number of organ systems. We showed previously that Nfia-deficient mice exhibit agenesis of the corpus callosum and other forebrain defects; Nfib-deficient mice have defects in lung maturation and show callosal agenesis and forebrain defects resembling those seen in Nfia-deficient animals, while Nficdeficient mice have defects in tooth root formation. Recently the Nfix gene has been disrupted and these studies indicated that there were largely uncharacterized defects in brain and skeletal development in Nfix-deficient mice. Results: Here we show that disruption of Nfix by Cre-recombinase mediated excision of the 2nd exon results in defects in brain development that differ from those seen in Nfia and Nfib KO mice. In particular, complete callosal agenesis is not seen in Nfix-/- mice but rather there appears to be an overabundance of aberrant Pax6- and doublecortin-positive cells in the lateral ventricles of Nfix-/- mice, increased brain weight, expansion of the cingulate cortex and entire brain along the dorsal ventral axis, and aberrant formation of the hippocampus. On standard lab chow Nfix-/- animals show a decreased growth rate from ~P8 to P14, lose weight from ~P14 to P22 and die at ~P22. If their food is supplemented with a soft dough chow from P10, Nfix-/- animals show a lag in weight gain from P8 to P20 but then increase their growth rate. A fraction of the animals survive to adulthood and are fertile. The weight loss correlates with delayed eye and ear canal opening and suggests a delay in the development of several epithelial structures in Nfix-/- animals. Conclusion: These data show that Nfix is essential for normal brain development and may be required for neural stem cell homeostasis. The delays seen in eye and ear opening and the brain morphology defects appear independent of the nutritional deprivation, as rescue of perinatal lethality with soft dough does not eliminate these defects

Variations in the structure of the prelunate gyrus in Old World monkeys

Anatomical and electrophysiological studies have revealed a complex organization in the macaque prelunate gyrus. We investigated the morphology and architecture of the prelunate gyrus in Old World monkeys. In Macaca nemestrina, we observed a sulcus crossing the prelunate gyrus within 2 mm of the vertical meridian representation. In other macaque species and other cercopithecines, we observed substantial variations in sulcal morphology across the prelunate gyrus. We did not find a sulcus in all species, and the location and depth of that indentation on the gyrus varied among species. A deep sulcus was observed in all species that emerged earlier in evolution than macaques, such as guenons, baboons, and colobines. We analyzed the regional and parcellation features of the prelunate gyrus in three macaque species, M. maura, M. mulatta, and M. radiata, and in Erythrocebus patas, with emphasis on the relation of structure to the distribution of prelunate visual areas. Nonphosphorylated neurofilament protein immunoreactivity permitted the delineation of a novel area in the prelunate gyrus of Old World monkeys, located around the prelunate sulcus. Species-specific patterns were also observed in the prelunate gyrus of the patas monkey compared to macaques. These observations, as well as a cladistic analysis of the data, suggest an expanded and diversified organization of the prelunate gyrus in some cercopithecoids that may reflect adaptation to specific ecological environments. It was, however, progressively lost in most macaques, being retained only in species that diverged early in the evolution of the genus Macaca, such as M. nemestrina and M. maura.status: publishe

Auditory brainstem response (ABR) group-average thresholds before and after high-level sound exposure.

<p>Unexposed rats are included for comparison. Post-exposure thresholds, obtained immediately after right ear exposure, show temporary right (exposed) ear elevation. End-of-study thresholds, obtained at the conclusion of psychophysical testing, show a recovery of exposed animals to normal threshold levels. Error bars in this and other figures indicates the standard error of the mean.</p

Doublecortin (DCX) immunoreactivity (IR) in UBCs of the DCN and cerebellum ipsilateral to the exposure.

<p><b>A.</b> Photomicrograph through the brainstem and cerebellum showing DCX-IR neurons. The rectangle shows the location of the higher magnification photomicrograph in B. <b>B.</b> DCX-IR in UBCs of the vPFL. <b>C.</b> DCX-IR neurons in the vPFL, FL and DCN on the side contralateral to the exposure. The rectangle shows the location of the photomicrograph in D. Scale bar 500 µm. <b>D.</b> DCX-IR neurons are UBCs, example at arrow. Scale bar 50 µm. Abbreviations: DCN, dorsal cochlear nucleus; FL, flocculus; UBC, unipolar brush cell vPFL. ventral paraflocculus.</p

Treatment Groups.

*<p>immunohistochemistry data unavailable for one animal.</p>**<p>See text for definition.</p

Experiment 2, glutamatergic antagonist effects on exposed rats with tinnitus.

<p>Glutamatergic antagonists were delivered to the ipsilateral PFL of exposed rats with significant evidence of tinnitus (triangular data points): Unexposed group results are depicted as circular data points and exposed non-drug animals as square data points. Pre-drug data are shown in the upper left panel. Exposed pre-drug animals were significantly downshifted from unexposed controls and were no different than exposed no-drug animals with tinnitus (repeated-measures F statistics shown in panel). After 72 hrs of antagonist cocktail, the treated animals were significantly up-shifted from the untreated exposed animals, therefore showing attenuation of tinnitus. Antagonist amelioration of tinnitus gradually waned over subsequent treatment days (bottom panels, left to right), returning to pre-treatment strength at 192 hrs.</p

Experiment 2 glutamatergic agonist effect on unexposed rats with no evidence of tinnitus.

<p>The glutamatergic agonist cocktail was delivered to the right PFL of unexposed rats with no evidence of tinnitus (open circular data points). Unexposed and exposed control groups are depicted as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064726#pone-0064726-g007" target="_blank">Figure 7</a>. Pre-drug data are shown in the upper left panel. The agonist cocktail induced a significant tinnitus-like downshift in the function of unexposed animals (upper right panel) after 72 hrs, although, as before, their tinnitus did not attain the same level as the exposed group with tinnitus (F statistics in panel). This tinnitus-like induction gradually washed out over the course of treatment (lower panels, left to right).</p