Densidad neuronal en la corteza visual primaria (área 17), en dos especies de octodon / Neuronal density in primary visual cortex (17 visual area), in two species of octodon

Estudios experimentales demuestran que modificaciones medioambientales pueden producir alteraciones en el desarrollo normal de la corteza cerebral visual y sus conexiones. Por otra parte, es posible que en condiciones naturales, las especies animales hayan desarrollado adaptaciones genéticas a las distintas condiciones de luminosidad en que realizan su actividad. Recientemente, se han observado variaciones significativas en la densidad neuronal cortical del área 17 (área visual primaria), en roedores silvestres con diferentes períodos diarios de actividad y relación filogenética distante (Abrothrix olivaceus y Phyllotis darwini), pero aún no se ha determinado la naturaleza genética o plástica de dichas diferencias. En este trabajo se compararon especies con una mayor cercanía filogenética, para disminuir al máximo la variable taxonómica. Se estudió la corteza visual primaria (área 17), de roedores silvestres nativos, de las especies Octodon degus (n=5) y Octodon bridgesi (n=3), pertenecientes a la Familia Octodontidae, con el propósito de evidenciar cambios a través de la medición de la densidad neuronal, mediante la técnica del disector óptico, en cortes de 40 µm, incluidos en celoidina y teñidos con Nissl. Complementariamente, se realizó una cuantificación de la densidad neuronal de la corteza motora de las especies en estudio. O. degus, que presenta un período de actividad diurna, evidenció una densidad neuronal menor en la corteza visual (34,32 +/- 2,51 x 104 neuronas/mm3), que la observada en O. bridgesi (39,55 +/- 0,64 x 104 neuronas/mm3), especie de período de actividad nocturna; lo cual fue estadísticamente significativo (t=3,44; p<0,05). Las diferencias encontradas se podrían relacionar con el tipo de condiciones de luminosidad en que se desenvuelven dichas especies, aunque no se puede descartar la influencia de otros factores.

Studies show that environmental modifications can produce profound alterations in the normal development of the visual cortex and its connectivity. For the other hand it is possible that in natural conditions, animal species have developed genetic adaptations to the different conditions of luminance in which they normally behave. Recently have observed significant changes in cortical neuronal density of area 17 (primary visual area), in two sympatric Chilean rodents with different daily activity (Phyllotis darwini and Abrothrix olivaceus), but have not yet determined the genetic nature or plastic such differences. In this paper we compared species with a closer phylogenetic relation so as to minimize the taxonomic variable. We studied the primary visual cortex (area 17) of wild rodents native of the species Octodon degus (n=5) and Octodon bridgesi (n=3), belonging to the Octodontidae family, in order to show changes in the neuronal density, using celloidin-embedded, 40µm-thickness Nissl sections, with the aid of an optical dissector. In addition, we performed a quantification of the neuronal density of the motor cortex of the species under study. O. degus, bearing a crepuscular-diurnal activity pattern, showed a lower neuronal density in the visual cortex (34.32 +/- 2.51 x10(4) neuron/mm³) than that observed in O. bridgesi (39.55 +/- 0.64 x10(4) neuron/mm³), a species that exhibits a nocturnal phase preference, which was statistically significant (t=3.44; p<0.05). These differences might be related to differences in daily activity in two species, but we cannot discount the influence of other factors.

Efecto de la Desnutrición Oculta Prenatal Sobre la Histología del Esplenio Callosal / Effect of Mild Protein Prenatal Malnutrition in the Callosal Splenium Histology

Ratas malnutridas prenatalmente con una dieta isocalórica y baja en proteínas, presentaron un menor diámetro axonal promedio en el esplenio callosal que los animales control, tanto de las fibras mielínicas como amielínicas. También se observó una mayor densidad axonal promedio, con respecto a los controles. Estas observaciones sugieren que: 1) las conexiones cortico-corticales (interhemisféricas) son vulnerables a la malnutrición proteica; y 2) lo anterior tendría incidencia en la velocidad de conducción interhemisférica, en particular con lo que dice relación con las conexiones visuales.

Adult rats malnourished prenatally with a low-protein, isocaloric diet showed smaller median fiber diameter of myelinated and unmyelinated fibers and a higher axonal density in the callosal splenium than controls. These findings suggest (i) that cortico-cortical (interhemispheric) connections are vulnerable to protein malnutrition; and (ii) this may affect interhemispheric conduction velocity, particularly in visual connections.

Densidad neuronal en la corteza visual primaria (area 17(, de dos especies de roedores silvestres / Neuronal density in primary visual cortex (17 visual area), in two wild rodent species

Diversos estudios experimentales demuestran que modificaciones medioambientales (por ejemplo: nutricionales y lumínicas), pueden producir alteraciones en el desarrollo normal de la corteza visual y sus conexiones. Por otro lado, es posible que en condiciones naturales, las especies animales hayan desarrollado adaptaciones a las distintas condiciones de luminosidad en que realizan su actividad. Por ende, la finalidad de este trabajo, fue estudiar la corteza visual primaria (área 17), de dos especies de roedores silvestres, relacionados filogenéticamente, pero con diferentes períodos de actividad; Abrothrix olivaceus (n=7) y Phyllotis darwini (n=7), con el propósito de evidenciar cambios detectados a través de la medición de la densidad neuronal, mediante la técnica del disector óptico, en cortes de 40µm de grosor, incluidos en celoidina y teñidos con cresyl violeta (Nissl). A. olivaceus, el cual presenta un periodo de actividad continuo en la zona central de Chile, evidenció una densidad neuronal menor (34.75 x 104 ± 1.35 x 104 neuronas/mm3) que la observada en P. darwini (37.23 x 104 ± 2.20 x 104 neuronas/mm3), especie de actividad nocturna en la misma región del país; siendo lo anterior estadísticamente significativo (t=2.54; p<0.05). Las diferencias encontradas se relacionarían con el tipo de conducta que presentan ambas especies, dado principalmente por las características de luminosidad en que se desenvuelven, así como también, de otros factores que se relacionarían con este parámetro, como son la relación predador-presa y la alimentación, entre otros.

Presencia de los alelos DRD4/7R y DAT1/10R en miembros de familias chilenas con síndrome de déficit atencional con hiperactividad / Presence of DRD4/7R and DAT1/10R allele in Chilean family members with attention deficit hyperactivity disorder

BACKGROUND: Genes for dopamine receptor DRD4 and dopamine transporter DAT1 have been implicated in attention deficit with hyperactivity disorder (ADHD). However, the findings are not conclusive. More studies in populations with different genetic backgrounds may contribute to solve the discrepancies observed. AIM: To test the hypothesis that affected members of Chilean families exhibit higher frequencies of the DRD4/7R and DAT1/10R alleles then their healthy sibs. MATERIAL AND METHODS: The parents of 51 children belonging to families of the Metropolitan Region of Chile, were approached to obtain clinical histories and blood samples, after the signature of a written informed consent. ADHD was diagnosed according to DSM-IV criteria, ancd intellectual coefficient was tested using the WISC-R test. Genomic DNA was extracted from lymphocytes and amplified by PCR. RESULTS: The 7R allele was identified in 13 out of 26 subjects diagnosed as ADHD and in 6 of 25 healthy sibs (p < 0.05). Parents with a history of ADHD, were conmpared with their healthy counterparts, exhibiting an identical tendency, that did not reach statistical significance. No significant differences in the frequencies of DAT1/10R alleles, were observed between cases and controls or their parents. CONCLUSIONS: Our results showed that ADHD in Chilean families is associated with the presence of DRD4/7R allele.

One hundred million years of interhemispheric communication: the history of the corpus callosum

Analysis of regional corpus callosum fiber composition reveals that callosal regions connecting primary and secondary sensory areas tend to have higher proportions of coarse-diameter, highly myelinated fibers than callosal regions connecting so-called higher-order areas. This suggests that in primary/secondary sensory areas there are strong timing constraints for interhemispheric communication, which may be related to the process of midline fusion of the two sensory hemifields across the hemispheres. We postulate that the evolutionary origin of the corpus callosum in placental mammals is related to the mechanism of midline fusion in the sensory cortices, which only in mammals receive a topographically organized representation of the sensory surfaces. The early corpus callosum may have also served as a substrate for growth of fibers connecting higher-order areas, which possibly participated in the propagation of neuronal ensembles of synchronized activity between the hemispheres. However, as brains became much larger, the increasingly longer interhemispheric distance may have worked as a constraint for efficient callosal transmission. Callosal fiber composition tends to be quite uniform across species with different brain sizes, suggesting that the delay in callosal transmission is longer in bigger brains. There is only a small subset of large-diameter callosal fibers whose size increases with increasing interhemispheric distance. These limitations in interhemispheric connectivity may have favored the development of brain lateralization in some species like humans. "...if the currently received statements are correct, the appearance of the corpus callosum in the placental mammals is the greatest and most sudden modification exhibited by the brain in the whole series of vertebrated animals..." T.H. Huxley (1)

Long distance communication in the human brain: timing constraints for inter-hemispheric synchrony and the origin of brain lateralization

Analysis of corpus callosum fiber composition reveals that inter-hemispheric transmission time may put constraints on the development of inter-hemispheric synchronic ensembles, especially in species with large brains like humans. In order to overcome this limitation, a subset of large-diameter callosal fibers are specialized for fast inter-hemispheric transmission, particularly in large-brained species. Nevertheless, the constraints on fast inter-hemispheric communication in large-brained species can somehow contribute to the development of ipsilateral, intrahemispheric networks, which might promote the development of brain lateralization.

Critical steps in the early evolution of the isocortex. Insights from developmental biology

This article proposes a comprehensive view of the origin of the mammalian brain. We discuss i) from which region in the brain of a reptilian-like ancestor did the isocortex originate, and ii) the origin of the multilayered structure of the isocortex from a simple-layered structure like that observed in the cortex of present-day reptiles. Regarding question i there have been two alternative hypotheses, one suggesting that most or all the isocortex originated from the dorsal pallium, and the other suggesting that part of the isocortex originated from a ventral pallial component. The latter implies that a massive tangential migration of cells from the ventral pallium to the dorsal pallium takes place in isocortical development, something that has not been shown. Question ii refers to the origin of the six-layered isocortex from a primitive three-layered cortex. It is argued that the superficial isocortical layers can be considered to be an evolutionary acquisition of the mammalian brain, since no equivalent structures can be found in the reptilian brain. Furthermore, a characteristic of the isocortex is that it develops according to an inside-out neurogenetic gradient, in which late-produced cells migrate past layers of early-produced cells. It is proposed that the inside-out neurogenetic gradient was partly achieved by the activation of a signaling pathway associated with the Cdk5 kinase and its activator p35, while an extracellular protein called reelin (secreted in the marginal zone during development) may have prevented migrating cells from penetrating into the developing marginal zone (future layer I)

La malnutrición prenatal proteica leve afecta el desarrollo del cuerpo callaso anterior / Mild protein prenatal malnutrition specifically affects development of the anterior corpus callosum

Ratas mal nutridas prenatalmente y durante la lactancia con una dieta isocalórica y baja en proteínas, presentaron un cuerpo calloso más pequeño que los controles, a los 45-52 días de edad, lo cual fue consistente con las diferencias en los pesos cerebrales. En cambio, ratas mal nutridas prenatalmente y rehabilitadas durante la lactancia con una dieta alta en proteínas, mostraron normalidad en el peso cerebral y en el desarrollo de los tercios medio y posterior del cuerpo calloso. Estas observaciones sugieren: 1) que las conexiones cortico-corticales (interhemisféricas) son vulnerables a la malnutrición proteica; y 2) el cuerpo calloso anterior, que conecta áreas frontales a través de la línea media, es particularmente afectado por este tipo de malnutrición, a pesar de una rehabilitación dietaria durante la vida postnatal.

Sexual dimorphism in interhemispheric relations: anatomical-behavioral convergencea

An embryogenetic hypothesis states that hemispheric specialization is inversely related to callosal connectivity (Geschwind and Galaburda, 1985). We tested this hypothesis (i) anatomically by relating postmortem planum temporale asymmetry to regional callosal morphology and (ii) behaviorally by relating the right visual field advantage in a lateralized lexical decision task with associative primes to regional callosal morphometry using magnetic resonance imaging (MRI). The postmortem study showed a significant negative correlation between planum temporale asymmetry and the number of small diameter fibers in the isthmus of the corpus callosum, but only for males. The MRI study showed a significant negative correlation between the right visual hemifield advantage for associated words and the cross section size of the isthmus of the corpus callosum, but again only in males. There was no sex difference in either the anatomical asymmetry, the behavioral asymmetry, or the callosal morphology. These convergent results suggest that there is a sexual dimorphism in interhemispheric relations in humans

Evolutionary origins of the reptilian brain: the question of putative homologues of dorsal ventricular ridge. An overview and proposal

The reptilian brain is characterized by a structure that bulges into the lateral ventricle, called dorsal ventricular ridge (DVR). The DVR was originally considered to be a part of the basal ganglia, although more recent studies indicate that it may correspond to the dorsal part of the hemisphere. The anterior portion of the DVR has several connectional and functional similarities with parts of the mammalian neocortex, for which reason it has been claimed that the two structures can be considered as homologues. In this article I review the evidence supporting and refuting homology of the DVR with different telencephalic structures of mammals, concluding that it is still early to unequivocally ascribe structural correspondences between the different components in the two vertebrate classes. However, a way out of the problem is suggested by comparing the embryonic position of DVR with that of lateral cortex in the reptilian hemisphere. The lateral cortex is considered to be quite comparable in reptiles and mammals, and hence may be a good marker for the original position of the DVR. If the DVR originates dorsal to lateral cortex, it may be considered comparable to parts of the mammalian neocortex, while if it develops in its same position or ventral to it, it may not correspond to the neocortex. Early embryological work indicated that the DVR develops in the same position as the lateral cortex, but arises as a late migration wave, after cells destined to lateral cortex are generated. In other words, instead of being interposed between dorsal and lateral cortices, the DVR may originate in a position overlapping with lateral cortex. If this alternative turns out to be the case, it may imply that the DVR arose de novo, through an extension of the ancestral period of neuroblast proliferation. As a consequence, there may be no structures comparable to it in other vertebrate classes. Finally, it is also proposed that, regardless of whether the DVR and the extrastriate neocortex can or cannot be considered phylogenetic homologues, some of the integrative functions performed by them might have a common evolutionary origin, that became localized in the reptilian DVR and in the mammalian extrastriate neocortex

The evolutionary origin of the mammalian cerebral cortex

The origin of the mammalian neocortex in usually considered as an improvement in the structure of the brain. Alternatively, I suggest that the mammalian neocortex arose as a consequence of contingent adaptations in which there was no specific selection for more elaborate cognitive abilities. In primitive mammals, the adaptation to nocturnal life produced a reduction of the optic tectum (superior colliculus). In addition, the development of the olfactory system triggered the development of the cerebral cortex. It is proposed that, since both the optic tectum and the cerebral cortex are laminar structures, the growing cortex replaced the tectum in many integratory functions. When mammals reinvaded diurnal niches, the optic tectum did not redevelop, and the cerebral cortex remained the main integratory and perceptual system. This is a case of irreversible reduction of an organ. In reptiles and especially in birds, although there was also an increase in brain size (associated with higher cognitive capacities), the optic tectum grew in size and complexity and the forebrain grew largely as a nonlaminar structure (except the Wulst in birds). Therefore, the origin of the cerebral cortex resulted from the combination of adaptations to nocturnality and the development of olfactory-driven behavior, and its origin is not directly related to higher cognitive capacities