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PubMed1997

The integrative neurobiology of affiliation. Introduction.

The research presented at this conference, including a series of excellent posters from junior investigators, documents the pervasive importance of affiliation and other social behaviors. Affiliative behaviors interact with, but are distinct from reproductive and aggressive behaviors. Patterns of social behaviors tend to be more species-typical than the behaviors associated with reproduction or aggression. However, neural circuits necessary for approach or avoidance also are necessary for the expression of various types of affiliative behavior such as maternal behavior or pair-bond formation. Furthermore, candidate neurochemical systems have been identified that contribute to various types of affiliative behavior. For example, studies revealing new behavioral functions for steroid hormones of the adrenal axis, such as corticosterone, and neuropeptides, including the endorphins, oxytocin and vasopressin, extend our general knowledge of neurobiology; they may also lead to studies that expand our understanding of social behavior and the connections to systems that regulate emotions. The work represented in this volume also has important implications for the study of serious neuropsychiatric disorders. For example, episodes of certain of these disorders can be induced by social stressors; in other disorders, a marked decrease in affiliative behaviors is a prominent feature of the patients' difficulties. Furthermore, abnormalities in animal systems implicated in the neurobiology of affiliation (oxytocin, vasopressin, and the hypothalamic-pituitary-adrenal system) have also been documented for major depression in humans. Animal models, such as those described at this conference, offer evolutionary perspectives, from which it is possible to extract general principles. At the same time, our understanding of the mechanistic and neurobiological substrates of both constructive and destructive social behaviors is increasing. At the conference, the evolutionary and mechanistic perspectives converged on the theme that studies of affiliative behaviors cannot be fully interpreted in isolation from other social behaviors; neither can they effectively be isolated from the biological and social contexts that shape their expression. Advances in this research area seem dependent on integrating experimental research across levels of analysis. Although this task is challenging, we are confident that an awareness of integrative principles can lead to new and important research opportunities.

Aggression↗
PubMed1997

Species diversity and the evolution of behavioral controlling mechanisms.

One of the first things that we are impressed by is the great variety of animals, particularly their behaviors and their physiologies. With so many differences, are there any generalities? With the establishment of evolutionary theory, evidence of "unity in diversity" comes with discoveries of common anatomical features, the cell cycle, conservation of intermediary metabolism, and the genetic code, to name but a few. In vertebrates there appears to be a conservation of the neural circuits underlying sexual behavior, but it is still too early to state the extent to which this concept can be extended to the hormonal mechanisms underlying behavior. Much of our conceptual understanding of behavioral neuroendocrinology stems from extensive studies on relatively few species. When an evolutionary perspective is applied to behavioral neuroscience, the breadth and validity of our assumptions about the mechanisms that control species-typical behaviors are challenged. This is not the same thing as saying that there are few unitary explanations that apply to all mammals, amniotes, or even vertebrates. Considerable information has been gathered about the neuroendocrine bases of behavior in a few species, but to uncover truly broad generalizations, we must look with equal intensity and rigor at other organisms. The pattern of evolution is best illustrated in the diversity of organisms, and the ecological and evolutionary perspective illuminates the utility of various "experiments of nature." By studying (1) closely related species that live in different habitats, we can see if the adaptational responses are similar, and (2) distantly related species that live in the same habitat, we can see if the solutions are analogous. The unique qualities of each species also give us a deeper understanding of the constraints in fundamental processes. When basic conflicts exist, control mechanisms adapt or the species goes extinct. Interestingly, although the neural circuits themselves do not degenerate, they are either no longer used or coopted for other functions.

Animals↗
PubMed1998

Identification and characterization of RNA editing events within the 5-HT2C receptor.

RNA editing is a post-transcriptional modification that generates an RNA transcript with a nucleotide sequence different from its gene. We have recently discovered RNA editing events, involving the conversion of adenosine bases to inosine residues, within the RNA encoding the serotonin 2C (5-HT2C) receptor. Editing events at four major positions, termed A, B, C and D, as well as one minor site termed C', are predicted to alter amino acids within the second intracellular loop of the G-protein coupled 5-HT2C receptor. Editing is mediated by at least two members of a family of adenosine deaminases and is contingent upon the presence of an extensive RNA duplex structure formed by exonic and intronic sequences of 5-HT2C receptor precursor messenger RNA (pre-mRNA). This critical secondary structure has been observed within brain pre-mRNA derived from four species; the isolation of edited 5-HT2C receptor transcripts from these samples further confirms the evolutionary conservation of this RNA processing event. Among members of the 5-HT2 receptor family, editing within second intracellular loop RNA is unique to the 5-HT2C receptor. Editing within the 5-HT2C receptor generates receptor isoforms that differ in their ability to interact with the phospholipase C signaling cascade in a transfected cell line, suggesting that this RNA processing event may contribute to the modulation of serotonergic neurotransmission in the central nervous system.

Amino Acid Sequence↗
PubMed2004

Serotonin transporter: gene, genetic disorders, and pharmacogenetics.

The highly evolutionarily conserved serotonin transporter (SERT) regulates the entire serotoninergic system and its receptors via modulation of extracellular fluid serotonin concentrations. Differences in SERT expression and function produced by three SERT genes and their variants show associations with multiple human disorders. Screens of DNA from patients with autism, ADHD, bipolar disorder, and Tourette's syndrome have detected signals in the chromosome 17q region where SERT is located. Parallel investigations of SERT knockout mice have uncovered multiple phenotypes that identify SERT as a candidate gene for additional human disorders ranging from irritable bowel syndrome to obesity. Replicated studies have demonstrated that the SERT 5'-flanking region polymorphism SS genotype is associated with poorer therapeutic responses and more frequent serious side effects during treatment with antidepressant SERT antagonists, namely, the serotonin reuptake inhibitors (SRIs).

Amino Acid Sequence↗
PubMed2003

Homo erectus calvarium from the Pleistocene of Java.

A Homo erectus calvarium [Sambungmacan 4 (Sm 4)] was recovered from Pleistocene sediments at Sambungmacan in central Java. Micro-computed tomography analysis shows a modern human-like cranial base flexion associated with a low platycephalic vault, implying that the evolution of human cranial globularity was independent of cranial base flexion. The overall morphology of Sm 4 is intermediate between that of earlier and later Javanese Homo erectus; apparent morphological specializations are more strongly expressed in the latter. This supports the hypothesis that later Pleistocene Javanese populations were substantially isolated and made minimal contributions to the ancestry of modern humans.

Animals↗