The ability to identify and retain logical relations between stimuli and apply them to novel stimuli is known as relational concept learning. This has been demonstrated in a few animal species after extensive reinforcement training, and it reveals the brain’s ability to deal with abstract properties. Here we describe relational concept learning in newborn ducklings without reinforced training. Newly hatched domesticated mallards that were briefly exposed to a pair of objects that were either the same or different in shape or color later preferred to follow pairs of new objects exhibiting the imprinted relation. Thus, even in a seemingly rigid and very rapid form of learning such as filial imprinting, the brain operates with abstract conceptual reasoning, a faculty often assumed to be reserved to highly intelligent organisms.
Filial imprinting in precocial birds is the process of forming a social attachment during a sensitive or critical period, restricted to the first few days after hatching. Imprinting is considered to be part of early learning to aid the survival of juveniles by securing maternal care. Here we show that the thyroid hormone 3,5,3'-triiodothyronine (T(3)) determines the start of the sensitive period. Imprinting training in chicks causes rapid inflow of T(3), converted from circulating plasma thyroxine by Dio2, type 2 iodothyronine deiodinase, in brain vascular endothelial cells. The T(3) thus initiates and extends the sensitive period to last more than 1 week via non-genomic mechanisms and primes subsequent learning. Even in non-imprinted chicks whose sensitive period has ended, exogenous T(3) enables imprinting. Our findings indicate that T(3) determines the start of the sensitive period for imprinting and has a critical role in later learning.
With the aim of elucidating the neural mechanisms of early learning, we studied the role of brain-derived neurotrophic factor (BDNF) in visual imprinting in birds. The telencephalic neural circuit connecting the visual Wulst and intermediate medial mesopallium is critical for imprinting, and the core region of the hyperpallium densocellulare (HDCo), situated at the center of this circuit, has a key role in regulating the activity of the circuit. We found that the number of BDNF mRNA-positive cells in the HDCo was elevated during the critical period, particularly at its onset, on the day of hatching (P0). After imprinting training on P1, BDNF mRNA-positive cells in the HDCo increased in number, and tyrosine phosphorylation of TrkB was observed. BDNF infusion into the HDCo at P1 induced imprinting, even with a weak training protocol that does not normally induce imprinting. In contrast, K252a, an antagonist of Trk, inhibited imprinting. Injection of BDNF at P7, after the critical period, did not elicit imprinting. These results suggest that BDNF promotes the induction of imprinting through TrkB exclusively during the critical period.
Sexual imprinting is important for kin recognition and for promoting outbreeding, and has been a driving force for evolution; however, little is known about sexual imprinting by auditory cues in mammals. Male mice emit song-like ultrasonic vocalizations that possess strain-specific characteristics.
Imprinting disorders (IDs) are a group of eight rare but probably underdiagnosed congenital diseases affecting growth, development and metabolism. They are caused by similar molecular changes affecting regulation, dosage or the genomic sequence of imprinted genes. Each ID is characterised by specific clinical features, and, as each appeared to be associated with specific imprinting defects, they have been widely regarded as separate entities. However, they share clinical characteristics and can show overlapping molecular alterations. Nevertheless, IDs are usually studied separately despite their common underlying (epi)genetic aetiologies, and their basic pathogenesis and long-term clinical consequences remain largely unknown. Efforts to elucidate the aetiology of IDs are currently fragmented across Europe, and standardisation of diagnostic and clinical management is lacking. The new consortium EUCID.net (European network of congenital imprinting disorders) now aims to promote better clinical care and scientific investigation of imprinting disorders by establishing a concerted multidisciplinary alliance of clinicians, researchers, patients and families. By encompassing all IDs and establishing a wide ranging and collaborative network, EUCID.net brings together a wide variety of expertise and interests to engender new collaborations and initiatives.
Visual experience sculpts whole-cortex spontaneous infraslow activity patterns through an Arc-dependent mechanism
- Proceedings of the National Academy of Sciences of the United States of America
- Published 21 days ago
Decades of work in experimental animals has established the importance of visual experience during critical periods for the development of normal sensory-evoked responses in the visual cortex. However, much less is known concerning the impact of early visual experience on the systems-level organization of spontaneous activity. Human resting-state fMRI has revealed that infraslow fluctuations in spontaneous activity are organized into stereotyped spatiotemporal patterns across the entire brain. Furthermore, the organization of spontaneous infraslow activity (ISA) is plastic in that it can be modulated by learning and experience, suggesting heightened sensitivity to change during critical periods. Here we used wide-field optical intrinsic signal imaging in mice to examine whole-cortex spontaneous ISA patterns. Using monocular or binocular visual deprivation, we examined the effects of critical period visual experience on the development of ISA correlation and latency patterns within and across cortical resting-state networks. Visual modification with monocular lid suturing reduced correlation between left and right cortices (homotopic correlation) within the visual network, but had little effect on internetwork correlation. In contrast, visual deprivation with binocular lid suturing resulted in increased visual homotopic correlation and increased anti-correlation between the visual network and several extravisual networks, suggesting cross-modal plasticity. These network-level changes were markedly attenuated in mice with genetic deletion of Arc, a gene known to be critical for activity-dependent synaptic plasticity. Taken together, our results suggest that critical period visual experience induces global changes in spontaneous ISA relationships, both within the visual network and across networks, through an Arc-dependent mechanism.
Exposure to distinct stimuli during critical periods of development can affect behavior long-term. A new study in Caenorhabditis elegans demonstrates that changes in neuronal activity of one synaptic connection following early-life pheromone exposure are sufficient to permanently enhance specific avoidance responses.
A selective, environmentally friendly, and cost-effective sample extraction method based on a combination of subcritical water extraction (SWE) and molecularly imprinted solid-phase extraction (MISPE) was developed for the determination of eight triazine herbicides in soil samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In SWE, the highest extraction yields of triazine herbicides were obtained under 150°C for 15min using 20% ethanol as the organic modifier. Addition of MIP during SWE increased the extraction efficiency, and using MIP as a selective SPE sorbent improved the enrichment capability. Soil samples were treated with the optimized extraction MIP/SWE-MISPE method and analyzed by LC-MS/MS. The novel technique was then applied to soil samples for the determination of triazine herbicides, and better recoveries (78.9%-101%) were obtained compared with using SWE-MISPE (30%-67%). Moreover, this newly developed method displayed good linearity (R(2)>0.99) and precision (2.7-9.8%), and low enough detection limits (0.4-3.3μgkg(-1)). This combination of SWE and MIP technology is a simple, effective and promising method to selectively extract class-specific compounds in complex samples.
Selective Removal of the Genotoxic Compound 2-Aminopyridine in Water using Molecularly Imprinted Polymers Based on Magnetic Chitosan and β-Cyclodextrin
- International journal of environmental research and public health
- Published 3 months ago
To develop efficient materials with enhanced adsorption and selectivity for genotoxic 2-aminopyridine in water, based on magnetic chitosan (CTs) and β-cyclodextrin (β-CD), the magnetic molecularly imprinted polymers (MMIPs) of Fe₃O₄-CTs@MIP and Fe₃O₄-MAH-β-CD@MIP were synthesized by a molecular imprinting technique using 2-aminopyridine as a template. The selective adsorption experiments for 2-aminopyridine were performed by four analogues including pyridine, aniline, 2-amino-5-chloropyridine and phenylenediamine. Results showed the target 2-aminopyridine could be selectively adsorbed and quickly separated by the synthesized MMIPs in the presence of the above structural analogues. The coexisting ions including Na⁺, K⁺, Mg(2+), Ca(2+), Cl(-) and SO₄(2-) showed little effect on the adsorption of 2-aminopyridine. The maximum adsorption capacity of 2-aminopyridine on Fe₃O₄-CTs@MIP and Fe₃O₄-MAH-β-CD@MIP was 39.2 mg·g(-1) and 46.5 mg·g(-1), respectively, which is much higher than values in previous reports. The comparison result with commercial activated carbon showed the obtained MMIPs had higher adsorption ability and selectivity for 2-aminopyridine. In addition, the synthesized MMIPs exhibited excellent performance of regeneration, which was used at least five times with little adsorption capacity loss. Therefore, the synthesized MMIPs are potential effective materials in applications for selective removal and analysis of the genotoxic compound aminopyridine from environmental water.
Due to the complexity of biological systems and samples, specific capture and targeting of certain biomolecules is critical in much biological research and many applications. cis-Diol-containing biomolecules, a large family of important compounds including glycoproteins, saccharides, nucleosides, nucleotides, and so on, play essential roles in biological systems. As boronic acids can reversibly bind with cis-diols, boronate affinity materials (BAMs) have gained increasing attention in recent years. However, real-world applications of BAMs are often severely hampered by three bottleneck issues, including nonbiocompatible binding pH, weak affinity, and difficulty in selectivity manipulation. Therefore, solutions to these issues and knowledge about the factors that influence the binding properties are of significant importance. These issues have been well solved by our group in past years. Our solutions started from the synthesis and screening of boronic acid ligands with chemical moieties favorable for binding at neutral and acidic pH. To avoid tedious synthesis routes, we proposed a straightforward strategy called teamed boronate affinity, which permitted facile preparation of BAMs with strong binding at neutral pH. To enhance the affinity, we confirmed that multivalent binding could significantly enhance the affinity toward glycoproteins. More interestingly, we observed that molecular interactions could be significantly enhanced by confinement within nanoscale spaces. To improve the selectivity, we investigated interactions that govern the selectivity and their interplays. We then proposed a set of strategies for selectivity manipulation, which proved to be useful guidelines for not only the design of new BAMs but also the selection of binding conditions. Applications in metabolomic analysis, glycoproteomic analysis, and aptamer selection well demonstrated the great potential of the prepared BAMs. Molecular imprinting is an important methodology for creating affinity materials with antibody-like binding properties. Boronate affinity-based covalent imprinting is a pioneering approach in molecular imprinting, but only a few cases of successful imprinting of glycoproteins by this method were reported. With sound understanding of boronate affinity, we developed two facile and generally applicable boronate affinity-based molecular imprinting approaches. The resulting boronate affinity molecularly imprinted polymers (MIPs) exhibited dramatically improved binding properties, including biocompatible binding pH range, enhanced affinity, improved specificity, and superb tolerance to interference. In terms of nanoconfinement effect, we explained why the binding pH range was widened and why the affinity was enhanced. The excellent binding properties made boronate affinity MIPs appealing alternatives to antibodies in promising applications such as disease diagnosis, cancer-cell targeting, and single-cell analysis. In this Account, we survey the key aspects of BAMs, the efforts we made to solve these issues, and the connections between imprinted and nonimprinted BAMs. Through this survey, we wish to pave a sound fundamental basis of the dependence of binding properties of BAMs on the nature and structure of the ligands and the supporting materials, which can facilitate the development and applications of BAMs. We also briefly sketch remaining challenges and directions for future development.