Consolidation of an Olfactory Memory Trace in the Olfactory Bulb Is Required for Learning-Induced Survival of Adult-Born Neurons and Long-Term Memory

Background: It has recently been proposed that adult-born neurons in the olfactory bulb, whose survival is modulated by learning, support long-term olfactory memory. However, the mechanism used to select which adult-born neurons following learning will participate in the long-term retention of olfactory information is unknown. We addressed this question by investigating the effect of bulbar consolidation of olfactory learning on memory and neurogenesis. Methodology/Principal Findings: Initially, we used a behavioral ecological approach using adult mice to assess the impact of consolidation on neurogenesis. Using learning paradigms in which consolidation time was varied, we showed that a spaced (across days), but not a massed (within day), learning paradigm increased survival of adult-born neurons and allowed long-term retention of the task. Subsequently, we used a pharmacological approach to block consolidation in the olfactory bulb, consisting in intrabulbar infusion of the protein synthesis inhibitor anisomycin, and found impaired learning and no increase in neurogenesis, while basic olfactory processing and the basal rate of adult-born neuron survival remained unaffected. Taken together these data indicate that survival of adult-born neurons during learning depends on consolidation processes taking place in the olfactory bulb. Conclusion/Significance: We can thus propose a model in which consolidation processes in the olfactory bulb determine both survival of adult-born neurons and long-term olfactory memory. The finding that adult-born neuron survival durin

Communication Impairments in Mice Lacking Shank1: Reduced Levels of Ultrasonic Vocalizations and Scent Marking Behavior

Autism is a neurodevelopmental disorder with a strong genetic component. Core symptoms are abnormal reciprocal social interactions, qualitative impairments in communication, and repetitive and stereotyped patterns of behavior with restricted interests. Candidate genes for autism include the SHANK gene family, as mutations in SHANK2 and SHANK3 have been detected in several autistic individuals. SHANK genes code for a family of scaffolding proteins located in the postsynaptic density of excitatory synapses. To test the hypothesis that a mutation in SHANK1 contributes to the symptoms of autism, we evaluated Shank1−/− null mutant mice for behavioral phenotypes with relevance to autism, focusing on social communication. Ultrasonic vocalizations and the deposition of scent marks appear to be two major modes of mouse communication. Our findings revealed evidence for low levels of ultrasonic vocalizations and scent marks in Shank1−/− mice as compared to wildtype Shank1+/+ littermate controls. Shank1−/− pups emitted fewer vocalizations than Shank1+/+ pups when isolated from mother and littermates. In adulthood, genotype affected scent marking behavior in the presence of female urinary pheromones. Adult Shank1−/− males deposited fewer scent marks in proximity to female urine than Shank1+/+ males. Call emission in response to female urinary pheromones also differed between genotypes. Shank1+/+ mice changed their calling pattern dependent on previous female interactions, while Shank1−/− mice were unaffected, indicating a failure of Shank1−/− males to learn from a social experience. The reduced levels of ultrasonic vocalizations and scent marking behavior in Shank1−/− mice are consistent with a phenotype relevant to social communication deficits in autism.National Institute of Mental Health (U.S.) (Intramural Research Program)Simons Foundatio

CBC/CDC Report on Governance, Structure, and Management: Frequently Asked Questions

A paper prepared by the Center Board Chairs and Center Directors to respond to frequently asked questions concerning the Report of the CBC/CDC Retreat, the Hague, 2-3 September 2000: Towards a Federation of Centers. This paper was circulated at CGIAR International Centers Week 2000 as background to the discussion of the organizational structure and governance of the CGIAR System

Scent marking behavior in the absence and presence of female urine in adult male <i>Shank1</i> mice.

<p>(A) Number of scent marks deposited near (within 10 cm² around) the female urine spot deposited by male subjects before they had an experience of social interactions with a female, and 7 days after they had a 5 minute experience of social interactions with a female. (B) Time spent in proximity to the female urine spot (10 cm²) by male subjects before they had an experience of social interactions with a female and after female experience. (C) Total number of scent marks deposited throughout the entire open field during the 5 min test session in the open field containing urine from a female C57BL/6J mouse deposited by male subjects before they had an experience of social interactions with a female and after female experience. (D) Total number of scent marks deposited throughout the entire open field during the 60 min habituation session in the clean open field without female urine deposited by male subjects before they had an experience of social interactions with a female and after female experience. Black bar: <i>Shank1^+/+</i> wildtype littermate control mice; striped bar: <i>Shank1^+/</i>⁻ heterozygote mice; white bar: <i>Shank1</i>^{−<i>/</i>−} null mutant mice. Data are presented as means ± standard errors of the mean. * p<0.050 vs. <i>Shank1^+/+</i>; # p<0.050 vs. <i>Shank1^+/</i>⁻.</p

Ultrasonic vocalizations in isolated <i>Shank1</i> pups.

<p>(A) Total number of ultrasonic vocalizations, (B) total calling time and (C) duration of calls emitted during the 5 min isolation from mother and littermates. (D) Time course for the number of ultrasonic vocalizations, (E) total calling time and (F) duration of calls emitted for each 1 min time bin across the 5 min isolation session. Black bar: <i>Shank1^+/+</i> wildtype littermate control mice; striped bar: <i>Shank1^+/</i>⁻ heterozygote mice; white bar: <i>Shank1</i>^{−<i>/</i>−} null mutant mice. For the sake of clarity, <i>Shank1^+/</i>⁻ heterozygote mice were not included in the time course graphs, while still included in the statistical analysis. Data are presented as means ± standard errors of the mean. * p<0.050 vs. <i>Shank1^+/+</i>; # p<0.050 vs. <i>Shank1^+/</i>⁻.</p

Body weight in <i>Shank1</i> mice.

<p>(A) Body weight in pups tested for isolation-induced ultrasonic vocalizations on postnatal day (pnd) 8. (B) Body weight in adult mice approximately 5 months of age. Black bar: <i>Shank1^+/+</i> wildtype littermate control mice; striped bar: <i>Shank1^+/</i>⁻ heterozygote mice; white bar: <i>Shank1</i>^{−<i>/</i>−} null mutant mice. Data are presented as means ± standard errors of the mean. * p<0.050 vs. <i>Shank1^+/+</i>; # p<0.050 vs. <i>Shank1^+/</i>⁻.</p

Open field activity in the absence and presence of female urine in adult male <i>Shank1</i> mice.

<p>(A) Total number of rearings and (B) distance traveled during the 60 min habituation session to the clean open field without female urine displayed by male subjects before they had an experience of social interactions with a female, and 7 days after they had a 5 minute experience of social interactions with a female. (C) Total number of rearings and (D) distance traveled during the 5 min test session in the same open field containing urine from a female C57BL/6J mouse displayed by male subjects before they had an experience of social interactions with a female and after female experience. Black bar: <i>Shank1^+/+</i> wildtype littermate control mice; striped bar: <i>Shank1^+/</i>⁻ heterozygote mice; white bar: <i>Shank1</i>^{−<i>/</i>−} null mutant mice. Data are presented as means ± standard errors of the mean. * p<0.050 vs. <i>Shank1^+/+</i>; # p<0.050 vs. <i>Shank1^+/</i>⁻.</p

Somatosensory reflexes in <i>Shank1</i> mice during early development.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0020631#pone-0020631-t002" target="_blank"></a>Data are expressed as means±SEM. PND =  postnatal day. [n] =  semi-quantitative rating (0 =  no response/not present, 1 =  slight response/slightly present, 2 =  strong response/strongly present, 3 =  incomplete response/incompletely present, and 4 =  complete adult-like response/presence). Effect of age: * p<0.050. Effect of genotype: # p<0.050. Effect of sex: NS. Interaction genotype x age: + p<0.050. Interaction sex x age: § p<0.050. Interaction genotype, sex and age: $ p<0.050. +/+ N = 9, +/− N = 11, −/− N = 16.</p

Developmental milestones in <i>Shank1</i> mice.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0020631#pone-0020631-t001" target="_blank"></a>Data are expressed as means±SEM. PND =  postnatal day. [n] =  semi-quantitative rating (0 =  no response/not present, 1 =  slight response/slightly present, 2 =  strong response/strongly present, 3 =  incomplete response/incompletely present, and 4 =  complete adult-like response/presence). Effect of age: * p<0.050. Effect of genotype: # p<0.050. Effect of sex: NS. Interaction genotype x age: + p<0.050. Interaction sex x age: § p<0.050. Interaction genotype, sex and age: $ p<0.050. +/+ N = 9, +/− N = 11, −/− N = 16.</p