Habituation in Aplysia: The Cheshire Cat of neurobiology

The marine snail, Aplysia californica, is a valuable model system for cell biological studies of learning and memory. Aplysia exhibits a reflexive withdrawal of its gill and siphon in response to weak or moderate tactile stimulation of its skin. Repeated tactile stimulation causes this defensive withdrawal reflex to habituate. Both short-term habituation, lasting <30 min, and long-term habituation, which can last >24 h, have been reported in Aplysia. Habituation of the withdrawal reflex correlates with, and is in part due to, depression of transmission at the monosynaptic connection between mechanoreceptive sensory neurons and motor neurons within the abdominal ganglion. Habituation-related short-term depression of the sensorimotor synapse appears to be due exclusively to presynaptic changes. However, changes within the sensory neuron, by themselves, do not account for more persistent depression of the sensorimotor synapse. Recent behavioral work suggests that long-term habituation in Aplysia critically involves postsynaptic processes, specifically, activation of AMPA- and NMDA-type receptors. In addition, long-term habituation requires activity of protein phosphatases, including protein phosphatases 1, 2A, and 2B, as well as activity of voltage-dependent Ca²⁺ channels. Cellular work has succeeded in demonstrating long-term, homosynaptic depression (LTD) of the sensorimotor synapse in dissociated cell culture and, more recently, LTD of the glutamate response of isolated motor neurons in culture (“hemisynaptic” LTD). These in vitro forms of LTD have mechanistic parallels to long-term habituation. In particular, homosynaptic LTD of the sensorimotor synapse requires elevated intracellular Ca²⁺ within the motor neuron, and hemisynaptic LTD requires activity of AMPA- and NMDA-type receptors. In addition, activation of group I and II metabotropic glutamate receptors (mGluRs) can induce hemisynaptic LTD. The demonstration of LTD in vitro opens up a promising new avenue for attempts to relate long-term habituation to cellular changes within the nervous system of Aplysia.     

基因突变不能为生物进化提供全部原料

目的：探讨基因突变能为进化产物有益影响的可能性,从而进一步支持生物物质、意识双轨制进化观点的正确性。方法：通过总结并充实现代生物学有关基因突变及生物进化的基本理论、特征及意义、指出原始意识的具体作用对原核细胞到真核细胞的进化事实进行剖析,从而提出基因突变不能为进化提供全部原料及其生物学依据。结论：基因突变不能为进化提供全部原料。     

The effect of punishment on a factor I stuttering behavior

On each of five days the subject of this experiment read aloud different material during an 18-min A₁ (base rate), B (experimental), and A₂ (extinction) period. No stimulation was delivered during the first three days. On the fourth day, the nonsense word “norg” was presented noncontingently during the experimental period. There was no statistically significant difference between the A₁ and B periods on any of these four days. On day five, “wrong” was made contingent on Factor I prolongations during the experimental period. As a result, there was a statistically significant increase in their frequency. When the response consequence was removed in the A₂ priod, there was a reliable reduction in prolongations and the frequency closely approximated that found in the A₁ period. These data suggest that response-contingent negative stimulation is contraindicated as a clinical tactic for use with Factor I prolongations. It not only failed to suppress them, it increased their frequency.     

Stuttering adaptation under distributed and massed conditions

An identical-subject-repeated-measures design, involving two counterbalanced conditions, was employed to investigate adaptation when the presentation of a 100-word list is distributed and when it is massed. In Condition I, the entire list was read aloud during each of five successive trials. Since a specific word reoccurred only after all of the others were displayed, the presentation may be said to be distributed. In contrast, the Condition II presentation was massed. Only after a word was read five times was the next one presented. The results indicate that significant adaptation occurred in both conditions. However, adaptation plateaued in the distributed condition. This was not the case when massing was employed. The among-condition analyses revealed that significantly more adaptation occurred in the massed than in the distributed condition.     

Identifying the interaction of maternal sensitivity and two serotonin-related gene polymorphisms on infant self-regulation

During infancy, orienting and gaze aversion serve as major self-regulatory mechanisms and play an important role in the development of deliberate self-regulation and control. The present study examined the interaction of intrinsic factors (MAOA-uVNTR and 5-HTTLPR gene polymorphisms) and extrinsic factors (maternal sensitivity) on early infant self-regulatory behavior. We assessed 5-HTTLPR (ss + sl versus ll) and MAOA-uVNTR (3 and 4 among boys, and 3/3, 3/4, and 4/4 among girls) polymorphisms, determined maternal sensitivity during mother–child free play, and coded infant self-regulatory behavior (i.e., orienting shifts in a temperament test) in 281 six-month-old infants. We found that infants who experienced a lower level of maternal sensitivity and had the short allele of 5-HTTLPR variants and the 3/3 MAOA-uVNTR polymorphism displayed lower self-regulation capacity than did those infants with a higher level of maternal sensitivity. This finding suggested a modulatory role of maternal sensitivity. Moreover, these findings are consistent with the genetic vulnerability hypothesis, which states that beneficial environmental factors serve as a buffer against harmful genetic predispositions during child development.     

Commentary Research on gene–environment interdependence: Honing the tools and examining the angles

The insightful overview by Sir Michael Rutter (this issue) on gene–environment interdependence comes about 10 years after the breakthrough Science publications on gene–environment interactions (G×E) involving the MAOA and 5-HTT genes by Caspi et al. (2002 Caspi, A., McClay, J., Moffitt, T. E., Mill, J., Martin, J.Craig, I. W. 2002. Role of genotype in the cycle of violence in maltreated children. Science, 297: 851–854. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar], 2003 Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W.Harrington, H. 2003. Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science, 301: 386–389. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]). Since then, a field of research has burgeoned that has produced replications as well as intriguing new evidence of gene–environment interdependence. At the same time, however, the field has witnessed a growing scepticism about the relevance of studying gene–environment interactions and has seen replication failures (see Duncan & Keller, 2011 Duncan, L. E. and Keller, M. C. 2011. A critical review of the first 10 years of candidate gene-by-environment interaction research in psychiatry. American Journal of Psychiatry, 168: 1041–1049. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]; Risch et al., 2009 Risch, N., Herell, R., Lehner, T., Liang, K.-Y., Eaves, L.Hoh, J. 2009. Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: A meta-analysis. Journal of the American Medical Association, 301: 2462–2471. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar]). Against this backdrop, we comment and elaborate on several of the key issues raised by Rutter, and suggest some directions for future research on G×E. Specifically, we discuss (1) replication issues; (2) the crucial role of experiments in understanding gene–environment interdependence; (3) current unknowns with regard to differential susceptibility; and (4) clinical and practical implications of G×E research.     

Examining cognitive development from a conceptual change point of view: The framework theory approach

Sexual socialization refers to how, through social interaction, an individual acquires and internalizes culture-specific knowledge, values and attitudes about sexuality. Little, however, is known about how an individual's genetic characteristics modify this process, or if individuals gravitate towards specific environments according to their genetic characteristics. The aim was to explore whether adolescents' genetic predispositions modify environmental influences on peer-group sexual attitudes. Using a Finnish population-based sample of twins and their siblings (n = 9534), it was found that genetic effects influenced peer-group sexual attitudes in men (52%) and women (46%), thus offering evidence for gene–environment correlation. Men showed less restricted peer-group sexual attitudes than women. Some indications of different genes influencing environmental exposure in men and women were found.     

Educational attainment-related loci identified by GWAS are associated with select personality traits and mathematics and language abilities

A recent genome-wide association study of educational attainment identified three significant single nucleotide polymorphisms (SNPs) (rs9320913, rs11584700, and rs4851266). In this study, we expanded this previous work by investigating behavioral correlates of these SNPs in a Han Chinese sample (rs9320913 was not available in our data and was thus replaced by rs12202969, which is in high linkage disequilibrium [i.e., correlations of alleles] with the former, r² = 0.96 in Han Chinese population based on the 1000 Genomes Project). Association analysis for individual SNPs showed significant associations between rs4851266 and a measure of language ability (Chinese word recognition), and between rs12202969 and a personality trait (fear of negative evaluation) and a measure of mathematical ability (number paired-associates learning). A polygenic score based on these three SNPs was also significantly associated with the measures of mathematical and language abilities. Specifically, educationally advantaged alleles identified in the previous study were associated with less fear of negative evaluation and higher mathematical and language abilities in the current study. This exploratory study provides evidence of psychological mechanisms for the association between genes and educational attainment.     

Gene flow by selective emigration as a possible cause for personality differences between small islands and mainland populations

Whether personality differences exist between populations is a controversial question. Even though such differences can be measured, it is still not clear whether they are due to individual phenotypic responses to the environment or whether they have a genetic influence. In a population survey we compared the personality traits of inhabitants of an Italian archipelago (the three Egadi islands; N = 622) with those of the closest mainland population (Trapani area; N = 106) and we found that personality differences between small populations can be detected. Islanders scored significantly lower on the personality traits of openness to experience and extraversion and higher on conscientiousness. We suggest that these personality trait differences could be an adaptive response to a confined socio‐environmental niche, genetically produced by a strong, non‐random gene flow in the last 20–25 generations, rather than the flexible response of islanders to environmental variables. To test this hypothesis, we compared subsets of the islander population classified by ancestry, birthplace, immigration and emigration and found that differences in extraversion can be accounted for by gene flow, while openness to experience and conscientiousness can also be accounted for by some gene–environment interactions. We propose a Personality Gene Flow hypothesis suggesting that, in small isolated communities, whenever there is strong, non‐random emigration, paired with weak and random immigration, we can expect rapid genetic personality change within the population. Copyright © 2010 John Wiley & Sons, Ltd.     

MTHFR and ACE gene polymorphisms and risk of vascular and degenerative dementias in the elderly

Focal lacunar infarctions due to cerebral small vessel atherosclerosis or single/multiple large cortical infarcts lead to vascular dementia, and different genes and environmental factors have been implicated in causation or aggravation of the disease. Previous reports suggest that some of the risk factors may be common to both vascular as well as degenerative dementia. Among genetic factors, role of angiotensin converting enzyme (ACE) and methylene-tetrahydrofolate reductase (MTHFR) genes as putative risk factors has been examined but the outcome of these studies remain inconclusive. Present study attempted to see the importance of ACE alu insertion/deletion and MTHFR C677T polymorphisms as genetic predisposers to dementia. The study comprised of 80 vascular dementia patients, 90 degenerative dementia patients and 170 age matched controls. All were genotyped for ACE, MTHFR and APOE polymorphisms using PCR-RFLP method. Frequency of ACE D allele was seemingly high in dementia cases (26.7%) when compared to controls (11.2%). However, after adjusting for age and APOE E4^*, none of the ACE alleles showed good correlation. MTHFR genotypes or alleles also did not show any correlation. Our study suggests no true correlation of ACE or MTHR genes with dementia in elderly.