Where Do Core Thalamocortical Axons Terminate in Mammalian Neocortex When There Is No Cytoarchitecturally Distinct Layer 4?

Although the mammalian cerebral cortex is most often described as a hexalaminar structure, there are cortical areas (primary motor cortex) and species (elephants, cetaceans, and hippopotami), where a cytoarchitecturally indistinct, or absent, layer 4 is noted. Thalamocortical projections from the core, or first order, thalamic system terminate primarily in layers 4/inner 3. We explored the termination sites of core thalamocortical projections in cortical areas and in species where there is no cytoarchitecturally distinct layer 4 using the immunolocalization of vesicular glutamate transporter 2, a known marker of core thalamocortical axon terminals, in 31 mammal species spanning the eutherian radiation. Several variations from the canonical cortical column outline of layer 4 and core thalamocortical inputs were noted. In shrews/microchiropterans, layer 4 was present, but many core thalamocortical projections terminated in layer 1 in addition to layers 4 and inner 3. In primate primary visual cortex, the sublaminated layer 4 was associated with a specialized core thalamocortical projection pattern. In primate primary motor cortex, no cytoarchitecturally distinct layer 4 was evident and the core thalamocortical projections terminated throughout layer 3. In the African elephant, cetaceans, and river hippopotamus, no cytoarchitecturally distinct layer 4 was observed and core thalamocortical projections terminated primarily in inner layer 3 and less densely in outer layer 3. These findings are contextualized in terms of cortical processing, perception, and the evolutionary trajectory leading to an indistinct or absent cortical layer 4.

Amplification of potential thermogenetic mechanisms in cetacean brains compared to artiodactyl brains.

To elucidate factors underlying the evolution of large brains in cetaceans, we examined 16 brains from 14 cetartiodactyl species, with immunohistochemical techniques, for evidence of non-shivering thermogenesis. We show that, in comparison to the 11 artiodactyl brains studied (from 11 species), the 5 cetacean brains (from 3 species), exhibit an expanded expression of uncoupling protein 1 (UCP1, UCPs being mitochondrial inner membrane proteins that dissipate the proton gradient to generate heat) in cortical neurons, immunolocalization of UCP4 within a substantial proportion of glia throughout the brain, and an increased density of noradrenergic axonal boutons (noradrenaline functioning to control concentrations of and activate UCPs). Thus, cetacean brains studied possess multiple characteristics indicative of intensified thermogenetic functionality that can be related to their current and historical obligatory aquatic niche. These findings necessitate reassessment of our concepts regarding the reasons for large brain evolution and associated functional capacities in cetaceans.

Organization of the sleep-related neural systems in the brain of the minke whale (Balaenoptera acutorostrata).

The current study analyzed the nuclear organization of the neural systems related to the control and regulation of sleep and wake in the basal forebrain, diencephalon, midbrain, and pons of the minke whale, a mysticete cetacean. While odontocete cetaceans sleep in an unusual manner, with unihemispheric slow wave sleep (USWS) and suppressed REM sleep, it is unclear whether the mysticete whales show a similar sleep pattern. Previously, we detailed a range of features in the odontocete brain that appear to be related to odontocete-type sleep, and here present our analysis of these features in the minke whale brain. All neural elements involved in sleep regulation and control found in bihemispheric sleeping mammals and the harbor porpoise were present in the minke whale, with no specific nuclei being absent, and no novel nuclei being present. This qualitative similarity relates to the cholinergic, noradrenergic, serotonergic and orexinergic systems, and the GABAergic elements of these nuclei. Quantitative analysis revealed that the numbers of pontine cholinergic (274,242) and noradrenergic (203,686) neurons, and hypothalamic orexinergic neurons (277,604), are markedly higher than other large-brained bihemispheric sleeping mammals. Small telencephalic commissures (anterior, corpus callosum, and hippocampal), an enlarged posterior commissure, supernumerary pontine cholinergic and noradrenergic cells, and an enlarged peripheral division of the dorsal raphe nuclear complex of the minke whale, all indicate that the suite of neural characteristics thought to be involved in the control of USWS and the suppression of REM in the odontocete cetaceans are present in the minke whale. J. Comp. Neurol. 524:2018-2035, 2016. © 2015 Wiley Periodicals, Inc.

In contrast to many other mammals, cetaceans have relatively small hippocampi that appear to lack adult neurogenesis.

The hippocampus is essential for the formation and retrieval of memories and is a crucial neural structure sub-serving complex cognition. Adult hippocampal neurogenesis, the birth, migration and integration of new neurons, is thought to contribute to hippocampal circuit plasticity to augment function. We evaluated hippocampal volume in relation to brain volume in 375 mammal species and examined 71 mammal species for the presence of adult hippocampal neurogenesis using immunohistochemistry for doublecortin, an endogenous marker of immature neurons that can be used as a proxy marker for the presence of adult neurogenesis. We identified that the hippocampus in cetaceans (whales, dolphins and porpoises) is both absolutely and relatively small for their overall brain size, and found that the mammalian hippocampus scaled as an exponential function in relation to brain volume. In contrast, the amygdala was found to scale as a linear function of brain volume, but again, the relative size of the amygdala in cetaceans was small. The cetacean hippocampus lacks staining for doublecortin in the dentate gyrus and thus shows no clear signs of adult hippocampal neurogenesis. This lack of evidence of adult hippocampal neurogenesis, along with the small hippocampus, questions current assumptions regarding cognitive abilities associated with hippocampal function in the cetaceans. These anatomical features of the cetacean hippocampus may be related to the lack of postnatal sleep, causing a postnatal cessation of hippocampal neurogenesis.

The ontogeny of sleep-wake cycles in zebrafish: a comparison to humans.

Zebrafish (Danio rerio) are used extensively in sleep research; both to further understanding of sleep in general and also as a model of human sleep. To date, sleep studies have been performed in larval and adult zebrafish but no efforts have been made to document the ontogeny of zebrafish sleep-wake cycles. Because sleep differs across phylogeny and ontogeny it is important to validate the use of zebrafish in elucidating the neural substrates of sleep. Here we describe the development of sleep and wake across the zebrafish lifespan and how it compares to humans. We find power-law distributions to best fit wake bout data but demonstrate that exponential distributions, previously used to describe sleep bout distributions, fail to adequately account for the data in either species. Regardless, the data reveal remarkable similarities in the ontogeny of sleep cycles in zebrafish and humans. Moreover, as seen in other organisms, zebrafish sleep levels are highest early in ontogeny and sleep and wake bouts gradually consolidate to form the adult sleep pattern. Finally, sleep percentage, bout duration, bout number, and sleep fragmentation are shown to allow for meaningful comparisons between zebrafish and human sleep.

Effects of individual glucose levels on the neuronal correlates of emotions.

This study aimed to directly assess the effect of changes in blood glucose levels on the psychological processing of emotionally charged material. We used functional magnetic resonance imaging (fMRI) to evaluate the effect of blood glucose levels on three categories of visually presented emotional stimuli. Seventeen healthy young subjects participated in this study (eight females; nine males; body weight, 69.3 ± 14.9 kg; BMI, 22 ± 2.7; age, 24 ± 3 years), consisting of two functional MRI sessions: (1) after an overnight fast under resting conditions (before glucose administration); (2) after reaching the hyperglycemic state (after glucose administration). During each session, subjects were presented with visual stimuli featuring funny, neutral, and sad content. Single-subject ratings of the stimuli were used to verify the selection of stimuli for each category and were covariates for the fMRI analysis. Analysis of the interaction effect of the two sessions (eu- and hyperglycemia), and the emotional categories accounting for the single-subject glucose differences, revealed a single activation cluster in the hypothalamus. Analysis of the activation profile of the left amygdala corresponded to the three emotional conditions, and this profile was obtained for both sessions regardless of glucose level. Our results indicate that, in a hyperglycemic state, the hypothalamus can no longer respond to emotions. This study offers novel insight for the understanding of disease-related behavior associated with dysregulation of glucose and glucose availability, potentially offering improved diagnostic and novel therapeutic strategies in the future.

Human hypocretin and melanin-concentrating hormone levels are linked to emotion and social interaction.

The neurochemical changes underlying human emotions and social behaviour are largely unknown. Here we report on the changes in the levels of two hypothalamic neuropeptides, hypocretin-1 and melanin-concentrating hormone, measured in the human amygdala. We show that hypocretin-1 levels are maximal during positive emotion, social interaction and anger, behaviours that induce cataplexy in human narcoleptics. In contrast, melanin-concentrating hormone levels are minimal during social interaction, but are increased after eating. Both peptides are at minimal levels during periods of postoperative pain despite high levels of arousal. Melanin-concentrating hormone levels increase at sleep onset, consistent with a role in sleep induction, whereas hypocretin-1 levels increase at wake onset, consistent with a role in wake induction. Levels of these two peptides in humans are not simply linked to arousal, but rather to specific emotions and state transitions. Other arousal systems may be similarly emotionally specialized.

[Ambulatory measuraments are better tolerated than in-hospital measuraments of sleep apnea.].

OBJECTIVE: This study compares self reported measures of sleep quality between groups of patients undergoing ambulatory or in-hospital annual control of Continuous Positive Airway Pressure (CPAP) therapy. METHODS: 70 consecutive Obstructive Sleep Apnea Syndrome (OSAS) patients scheduled for an annual control of CPAP therapy were randomly assigned to either ambulatory or in the hospital conditions. The same recording equipment was used in both conditions. RESULTS: Overall the ambulatory group slept better, had less difficulties falling asleep, and was less anxious about the study than the in-hospital group. CONCLUSION: The results provide one reason for regarding ambulatory recordings more favourably than similar registration done in-hospital.

Hippocampal theta in the newborn rat is revealed under conditions that promote REM sleep.

Hippocampal theta activity, a high-amplitude, slow (4-12 Hz) oscillation that occurs in a variety of behavioral contexts, is thought to emerge in infant rats only after 1 week of age. However, we report here that unanesthetized 2- and 4-d-old rats with electrodes implanted in the CA1 field of the hippocampus and tested in thermoneutral conditions exhibit theta activity. Moreover, this infant theta is characterized by the same neuronal bursting pattern and power spectrum that characterize theta in adults. Simultaneous measures of behavior and neck muscle tone indicated that bouts of theta occurred predominantly during periods of muscle atonia (with or without concurrent myoclonic twitching), indicative of REM sleep. In contrast, sharp waves were accompanied by startles (i.e., simultaneous and vigorous movement of all four limbs). These findings underscore the need for comprehensive in vivo investigations of the pharmacology, neural substrates, and behavioral correlates of hippocampal field activity in neonates.