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Evolution of GABAergic circuitry in the mammalian medial geniculate body.

Many features in the mammalian sensory thalamus, such as the types of neurons, their connections, or their neurotransmitters, are conserved in evolution. We found a wide range in the proportion of gamma-aminobutyric acidergic (GABAergic) neurons in the medial geniculate body, from <1% (bat and rat) to 25% or more (cat and monkey). In the bat, some medial geniculate body subdivisions have no GABAergic cells. Species-specific variation also occurs in the somesthetic ventrobasal complex. In contrast, the lateral geniculate body of the visual system has about the same proportion of GABAergic cells in many species. In the central auditory pathway, only the medial geniculate body shows this arrangement; the relative number of GABAergic cells in the inferior colliculus and auditory cortex is similar in each species. The range in the proportion of GABAergic neurons suggests that there are comparative differences in the neural circuitry for thalamic inhibition. We conclude that the number of GABAergic neurons in thalamic sensory nuclei may have evolved independently or divergently in phylogeny. Perhaps these adaptations reflect neurobehavioral requirements for more complex, less stereotyped processing, as in speech-like communication.

Animals↗

The adaptive nature of the human neurocognitive architecture: an alternative model.

The model of the human neurocognitive architecture proposed by evolutionary psychologists is based on the presumption that the demands of hunter-gatherer life generated a vast array of cognitive adaptations. Here we present an alternative model. We argue that the problems inherent in the biological markets of ancestral hominids and their mammalian predecessors would have required an adaptively flexible, on-line information-processing system, and would have driven the evolution of a functionally plastic neural substrate, the neocortex, rather than a confederation of evolutionarily prespecified social cognitive adaptations. In alignment with recent neuroscientific evidence, we suggest that human cognitive processes result from the activation of constructed cortical representational networks, which reflect probabilistic relationships between sensory inputs, behavioral responses, and adaptive outcomes. The developmental construction and experiential modification of these networks are mediated by subcortical circuitries that are responsive to the life history regulatory system. As a consequence, these networks are intrinsically adaptively constrained. The theoretical and research implications of this alternative evolutionary model are discussed.

Adaptation, Biological↗

High complexity in the expression of the B' subunit of protein phosphatase 2A0. Evidence for the existence of at least seven novel isoforms.

Association of the catalytic subunit (C2) with a variety of regulatory subunits is believed to modulate the activity and specificity of protein phosphatase 2A (PP2A). In this study we report the cloning and expression of a new family of B-subunit, the B', associated with the PP2A0 form. Polymerase chain reactions and cDNA library screening have identified at least seven cDNA isotypes, designated alpha, beta 1, beta 2, beta 3, beta 4, gamma, and delta. The different beta subtypes appear to be generated by alternative splicing. The deduced amino acid sequences of the alpha, beta 2, beta 3, beta 4 and gamma isoforms predict molecular weights of 57,600, 56,500, 60,900, 52,500, and 68,000, respectively. The proteins are 60-80% identical and differ mostly at their termini. Two of the isoforms, B' beta 3 and B' gamma, contain a bipartite nuclear localization signal in their COOH terminus. No homology was found with other B- or B- related subunits. Northern analyses indicate a tissue-specific expression of the isoforms. Expression of B' alpha protein in Escherichia coli generated a polypeptide of approximately 53 kDa, similar to the size of the B' subunit present in the purified PP2A0. The recombinant protein was recognized by antibody raised against native B' and interacted with the dimeric PP2A (A.C2) to generate a trimeric phosphatase. The deduced amino acid sequences of the B' isoforms show significant homology to mammalian, fungal, and plant nucleotide sequences of unknown function present in the data bases. Notably, a high degree of homology (55-66%) was found with a yeast gene, RTS1, encoding a multicopy suppressor of a rox3 mutant. Our data indicate that at least seven B' subunit isoforms may participate in the generation of a large number of PP2A0 holoenzymes that may be spatially and/or functionally targeted to different cellular processes.

Amino Acid Sequence↗

Very large G protein-coupled receptor-1, the largest known cell surface protein, is highly expressed in the developing central nervous system.

We previously identified a member of the G protein-coupled receptor family, very large G protein-coupled receptor-1 (VLGR1). VLGR1 has a large ectodomain containing multiple calcium exchanger beta repeats that resemble regulatory domains of sodium-calcium exchanger proteins. Similar repeats are found in the extracellular aggregation factor of marine sponges, which mediates species-specific cell aggregation. We now report that the protein encoded by the originally described human cDNA (now termed VLGR1a) is, in fact, at 1967 amino acids, the smallest of three expressed human isoforms. It is encoded by an alternative transcript that begins within intron 64 of the VLGR1 gene. The longest gene product, VLGR1b, is 6307 amino acids (6298 amino acids in mice) due to a much larger ectodomain containing 35 calcium exchanger beta repeats and a pentraxin homology domain. VLGR1b is apparently the largest known cell surface protein. The VLGR1 gene comprises 90 exons and is >600 kb long. In situ hybridization studies with mouse embryo sections show that high level expression of VLGR1 is restricted to the developing central nervous system and eye. Strong expression in the ventricular zone, home of neural progenitor cells during embryonal neurogenesis, suggests a fundamental role for VLGR1 in the development of the central nervous system.

Amino Acid Sequence↗

Have dual survival systems created the human mind?

This article reviews pertinent psychological theory to argue for two discrete human motivational tracts. These dual systems appear to draw from disparate constellations of emotional energies that normatively become interactive across development. The article stipulates eight premises from the accepted tenets of psychology, development, and pathology along with corroborating evidence from laterality studies, neuropsychology, and the neurosciences. These premises lead to a verifiable hypothesis reflecting Richard Leakey's proposal that H. sapiens emerged from an interpersonal shaping of adaptation across several million years of group living. The totality of the supportive evidence suggests that the flexibility, agility, and creativity of the human mind was abetted by tensions and reconciliations between two disparate hemispheric perspectives, which express as a Personal Self and a Social Self, focused by a lens molded by survival pressures.

Adaptation, Physiological↗

Associative agnosias and the functions of the left hemisphere.

Associative agnosias are traditionally regarded as perceptual, and ideational apraxia as motor, deficits, but they can be understood as amnesias for generic knowledge, caused by bilateral or unilateral left-hemispheric cortical lesions. Current theories of hemispheric specialization explain these syndromes' mandatory link with left-hemispheric damage, and are validated by this link. This link reflects the multiple nature of generic, categorical representational systems, not all reducible to natural language, and the left hemisphere's principal role as their substrate, regardless of their dependence on language. The distinction between processing novel information, and processing based on well-established, routinized representations, captures a fundamental difference between the functions of the right and left hemispheres. The complementary link of apperceptive agnosias with right-and associative agnosias with left-hemisphere lesions is an expression of this general principle in the posterior cortex. Future studies of the neuroanatomy of agnosias in animals may offer insights into the evolutionary continuities of hemispheric specialization.

Agnosia↗

Assessing recovery in middle cerebral artery stroke using functional MRI.

PRIMARY OBJECTIVE: To understand the temporal evolution of brain reorganization during recovery from stroke. RESEARCH DESIGN: A patient who suffered left middle cerebral artery stroke 9 months earlier was studied on three occasions, approximately 1 month apart. METHODS AND PROCEDURES: Brain activation was studied using functional Magnetic Resonance Imaging (fMRI). During each session, the patient performed a finger-to-thumb opposition task, which involved one bimanual and two unimanual conditions. Each condition consisted of overt movement of fingers and imagery of the same task. RESULTS: With recovery, greater recruitment was observed of the affected primary motor cortex (M1) and a decrease in activation of the unaffected M1 and supplementary motor area. In addition, the widespread activation of brain areas seen during the initial session changed to a more focused pattern of activation as the patient recovered. Imagery tasks resulted in similar brain activity as overt execution pointing to imagery as a potential tool for rehabilitation.

Aged↗

Advances in understanding the anxiety disorders: the cognitive-affective neuroscience of 'false alarms'.

BACKGROUND: There have been significant advances in our understanding of the anxiety disorders; a range of data is now available on their epidemiology, nosology, psychobiology, and management. An integrative framework is required in order to conceptualize this data and to apply it in the clinic. METHODS: This is a nonsystematic review of literature on the psychobiology of some the major anxiety disorders, focused on the idea that each of these conditions can be conceptualized in terms of a different "false alarm," mediated by specific neurocircuitry and with a particular evolutionary origin. RESULTS: The "false alarm" concept is able to integrate a range of data on the proximal mechanisms of anxiety disorders (including their mediating neurochemistry and neurogenetics), as well as hypotheses about the distal or evolutionary underpinnings of these conditions. CONCLUSION: Fortunately, serotonergic antidepressants and cognitive-behavioral psychotherapy appear to be able to normalize the putative "false alarms" in anxiety disorders. A better understanding of the cognitive-affective neuroscience of anxiety disorders will hopefully lead to improved treatments.

Affect↗

The layers of presence: a bio-cultural approach to understanding presence in natural and mediated environments.

This paper proposes a bio-cultural theory of presence based on four different positions related to the role and structure of presence, as follows. First, presence is a defining feature of self and it is related to the evolution of a key feature of any central nervous system: the embedding of sensory-referred properties into an internal functional space. Without the emergence of the sense of presence it is impossible for the nervous system to experience distal attribution: the referencing of our perception to an external space beyond the limits of the sensory organs themselves. Second, even if the experience of the sense of presence is a unitary feeling, conceptually it can be divided in three different layers, phylogenetically different and strictly related to the three levels of self identified by Damasio. In particular we can make conceptual distinctions between proto presence (self vs. non self), core presence (self vs. present external world), and extended presence (self relative to present external world). Third, given that each layer of presence solves a particular facet of the internal/external world separation, it is characterized by specific properties. Finally, in humans the sense of presence is a direct function of these three layers: the more they are integrated, the more we are present. In the experience of optimal presence, biologically and culturally determined cognitive processes are working in harmony--to focus all levels of the self on a significant situation in the external world, whether this is real or virtual.

Animals↗

A longitudinal fMRI study on motor activity in patients with multiple sclerosis.

Using functional MRI (fMRI), patients with multiple sclerosis showed a greater extent of motor activation than controls. Although functional changes are often interpreted as adaptive and as a contributing factor in limiting the clinical deficit, no longitudinal studies have yet been performed for multiple sclerosis. Sixteen patients with multiple sclerosis, two patients with possible multiple sclerosis and nine age-matched controls underwent two fMRI studies with a time interval of 15-26 months. The motor task consisted of a self-paced sequential finger opposition movement with the right hand. Patients with multiple sclerosis exhibited greater bilateral activation than controls in both fMRI studies. At follow-up, patients showed a reduction in functional activity in the ipsilateral sensorimotor cortex and in the contralateral cerebellum. No significant differences between the two fMRI studies were observed in controls. Activation changes in ipsilateral motor areas correlated inversely with age, extent and progression of T1 lesion load, and occurrence of a new relapse. This study may help the understanding of the evolution of brain plastic changes in multiple sclerosis indicating that, in younger patients with a less structural brain damage and benign clinical course, the brain reorganizes its functional activity towards a more lateralized pattern of brain activation. The tendency towards a normalization of brain functional activity is hampered in older patients and in those developing relapses or new irreversible brain damage.

Adult↗

Evolutionary conservation in the untranslated regions of actin mRNAs: DNA sequence of a human beta-actin cDNA.

We report the complete nucleotide sequence of a human beta actin cDNA. Both the 5' and 3' untranslated regions of the sequence are similar (greater than 80%) to the analogous regions of the rat beta-actin gene reported by Nudel et al (1983). When a segment of the 3' untranslated region is used as a radiolabelled probe, strong hybridization to chick beta actin mRNA is seen. This conservation of sequences suggests that strong selective pressures operate on non-translated segments of beta actin mRNA.

Actins↗

Correcting parsimonious trees for unseen nucleotide substitutions: the effect of dense branching as exemplified by ribonuclease.

In a study of mammalian ribonuclease evolutionary rates, we applied the Fitch-Bruschi correction to reduce the bias caused by an unequal sampling of taxa in different lineages. The correction was clearly appropriate but only up to a point. The analysis showed that the sampling of taxa within the pecora was sufficiently intense that no correction for unseen, amino acid-changing, nucleotide substitutions was required. It was also found that the ribonuclease gene was duplicated at least twice at the origin of the pecoran branch of the artiodactyls.

Animals↗

Jaws.

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Animals↗

Temporolimbic or transcallosal connections: where is the primary lesion in schizophrenia and what is its nature?

A critique of the article by Bogerts on the temporolimbic system theory is presented. Schizophrenia is conceived as arising as a component of the diversity of interhemisphric (callosal) connectivity associated with the evolution of language, a process that occurred through a genetic change (the speciation event) that allowed the hemispheres to develop with a degree of independence. Language and psychosis thus have a common evolutionary origin. The anatomical changes can be considered as a boundary component of the anatomical variation that is characteristic of the species.

Biological Evolution↗

Intraoperative imaging in glioblastoma resection.

The use of intraoperative imaging (IOI) in neurosurgical practice is proving to be yet another important advance in the evolution of brain tumor resection, particularly for the most common adult primary brain tumor--glioblastoma (GBM). The number of surgeons using IOI continues to increase, and the experience to date affords an opportunity to assess the value of the various techniques used for IOI.

Brain Neoplasms↗

An exaggerated preference for simple neural network models of signal evolution?

Recently, simple neural network models have been used to explain the evolution of important phenomena in animal signalling, such as extravagant ornamentation and symmetrical signals, as responses to inevitable 'hidden preferences' of recognition systems. We argue that these very simple models may be misleading because they may not behave in important ways like the recognition systems of real animals and so cannot justify their claim to demonstrate general principles of perception in a signalling context. We show that the way in which these simple models respond to exaggerated signals may not be, as is claimed, a close parallel to the phenomena of peak shift or supernormal responses. We also argue that the preference for symmetrical patterns shown by the models is unlikely to reflect the way computationally that real animals solve problems of pattern invariance and may be an artefact of the particular way the models have been set up. Whereas more sophisticated neural net models do capture known properties of real visual systems and are consequently of great use in understanding perception, the same cannot be said of very simple one-dimensional models with small numbers of units and connections. Given the far reaching explanatory claims made of these simpler models their limitations should be more widely recognized.

Animal Communication↗