Elevated expression of brain‐derived neurotrophic factor facilitates visual imprinting in chicks

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.     

Activation of cholecystokinin neurons in the dorsal pallium of the telencephalon is indispensable for the acquisition of chick imprinting behavior

Chick imprinting behavior is a good model for the study of learning and memory. Imprinting object is recognized and processed in the visual wulst, and the memory is stored in the intermediate medial mesopallium in the dorsal pallium of the telencephalon. We identified chicken cholecystokinin (CCK)-expressing cells localized in these area. The number of CCK mRNA-positive cells increased in chicks underwent imprinting training, and these cells expressed nuclear Fos immunoreactivity at high frequency in these regions. Most of these CCK-positive cells were glutamatergic and negative for parvalbumin immunoreactivity. Semi-quantitative PCR analysis revealed that the CCK mRNA levels were significantly increased in the trained chicks compared with untrained chicks. In contrast, the increase in CCK- and c-Fos-double-positive cells associated with the training was not observed after closure of the critical period. These results indicate that CCK cells in the dorsal pallium are activated acutely by visual training that can elicit imprinting. In addition, the CCK receptor antagonist significantly suppressed the acquisition of memory. These results suggest that the activation of CCK cells in the visual wulst as well as in the intermediate medial mesopallium by visual stimuli is indispensable for the acquisition of visual imprinting.     

Neural bases of recognition memory investigated through an analysis of imprinting

Through a learning process known as imprinting, the young of some animals, including the domestic chick, come to recognize an object by being exposed to it. Visually naive chicks vigorously approach a wide range of objects. After an adequate period of exposure to one object chicks selectively approach it in a recognition test. The nervous system of dark-reared chicks is not a tabula rasa, as chicks have predispositions to approach some stimuli rather than others. Nevertheless, visual imprinting leads to changes in a nervous system that may not have been 'marked' by previous visual experience, and so encourages the hope of discovering the neural bases of the learning process. The intermediate and medial part of the hyperstriatum ventrale, a sheet of cells within the cerebral hemispheres, plays a crucial role in visual imprinting, particularly in the memory process of recognition. The cellular and sub-cellular changes that take place in this part of the hyperstriatum ventrale after imprinting are described. The right and left hyperstriatum ventrale regions play different roles in the imprinting process, and evidence is given for the existence of multiple memory systems in the chick brain.     

The present state in the phylogeny and ontogeny of hormone receptors

Presence of signal receivers (for food, toxic, substances, "hostile" cells etc.) is essential at all levels of phylogenesis. The first encounter of a "hormone to be" with an aspecific membrane structure ("receptor to be") could result in the formation of a lasting receptor-hormone connection if it is adventageous for the cell or organism (which contains the cell), during phylogeny. At higher levels of phylogenesis receptors (ontogenetically) develop according to the differentiation program of the cell, however reinforcement (by the hormone) is necessary in a critical (neonatal) period of receptor development. This is the hormonal imprinting. In that time the receptor could be damaged by the presence of molecules analogous to the hormone. The hormonal imprinting belongs to the perinatal recognition mechanisms of organisms. The possible mechanisms of receptor development are also discussed.     

Neuronal plasticity and multisensory integration in filial imprinting

Many organisms sample their environment through multiple sensory systems and the integration of multisensory information enhances learning. However, the mechanisms underlying multisensory memory formation and their similarity to unisensory mechanisms remain unclear. Filial imprinting is one example in which experience is multisensory, and the mechanisms of unisensory neuronal plasticity are well established. We investigated the storage of audiovisual information through experience by comparing the activity of neurons in the intermediate and medial mesopallium of imprinted and naïve domestic chicks (Gallus gallus domesticus) in response to an audiovisual imprinting stimulus and novel object and their auditory and visual components. We find that imprinting enhanced the mean response magnitude of neurons to unisensory but not multisensory stimuli. Furthermore, imprinting enhanced responses to incongruent audiovisual stimuli comprised of mismatched auditory and visual components. Our results suggest that the effects of imprinting on the unisensory and multisensory responsiveness of IMM neurons differ and that IMM neurons may function to detect unexpected deviations from the audiovisual imprinting stimulus.     

BDNF regulates the maturation of inhibition and the critical period of plasticity in mouse visual cortex.

Maturation of the visual cortex is influenced by visual experience during an early postnatal period. The factors that regulate such a critical period remain unclear. We examined the maturation and plasticity of the visual cortex in transgenic mice in which the postnatal rise of brain-derived neurotrophic factor (BDNF) was accelerated. In these mice, the maturation of GABAergic innervation and inhibition was accelerated. Furthermore, the age-dependent decline of cortical long-term potentiation induced by white matter stimulation, a form of synaptic plasticity sensitive to cortical inhibition, occurred earlier. Finally, transgenic mice showed a precocious development of visual acuity and an earlier termination of the critical period for ocular dominance plasticity. We propose that BDNF promotes the maturation of cortical inhibition during early postnatal life, thereby regulating the critical period for visual cortical plasticity.     

Evidence for a critical period for imprinting in khaki campbell ducklings (Anas platyrhynchos domesticus)

In an attempt to simulate certain aspects of a natural setting, newly hatched and 5-day-old ducklings were exposed to an imprinting stimulus under conditions where flight from the stimulus completely removed them from its presence. The results indicated that while the younger subjects tended to approach the stimulus, the older ducklings rapidly and persistently escaped from it. In a second study, older ducklings were denied the opportunity to escape from the imprinting stimulus. Under these conditions the flight reaction waned and the subjects began to approach the stimulus. The overall pattern of results are consistent with the concept of a critical period for imprinting.     

单细胞动物和多细胞动物的激素印迹

激素印迹是单细胞动物和多细胞动物的一种生理现象,也是选择参与信号识别过程分子的工具。激素印迹后,受体记忆将遗传给子孙后代,因此其对进化的作用可能是很大的。同时,激素印迹还有利于物种的维持。另外,激素印迹过程还是具有终身效应的临时开放系统的一部分。没有印迹,就没有完全的受体成熟,而不成熟的受体是不能和适量的激素结合的。在围 期诸如治疗药物和环境污染剂等人工合成的物质分子易致错误或病理印迹。许多研究表明错误印迹对生物体具有重要的影响。当然,单细胞动物的激素印迹过程与多细胞动物并不完全一样。     

MECHANISMS OF AVIAN IMPRINTING: A REVIEW

Filial imprinting is the process through which early social preferences become restricted to a particular object or class of objects. Evidence is presented showing that filial preferences are formed not only as a result of learning through exposure to an object, but also under the influence of visual and auditory predispositions. The development of these predispositions is dependent upon certain non-specific experience. There is little evidence for an endogenously affected sensitive period for imprinting. It is more likely that the end of sensitivity is a result of the imprinting process itself. Similarly, it is now firmly established that filial and sexual preferences are reversible. Evidence suggests, however, that the first stimulus to which the young animal is exposed may exert a greater influence on filial preferences than subsequent stimuli. The learning process of imprinting is often regarded as being different from conventional associative learning. However, the imprinting object itself can function as a reinforcer. Recent studies have attempted to test predictions from an interpretation of filial imprinting as a form of associative learning. The first results suggest that ‘blocking’ may occur in imprinting, whilst there is no evidence for ‘overshadowing’. Social interactions with siblings and parent(-surrogates) have been shown to affect the formation of filial and sexual preferences. The influence of these interactions is particularly prominent in sexual imprinting, making earlier claims about naive species-specific biases unlikely. Although auditory stimuli play an important role in the formation of social attachments, there is little evidence for auditory imprinting per se. Auditory preferences formed as a result of mere (pre- or postnatal) exposure are relatively weak and short-lasting. Exposure to visual stimuli during auditory training significantly improves auditory learning, possibly through a process of reinforcement. It is becoming increasingly clear that filial and sexual imprinting are two different (although perhaps analogous) processes. Different mechanisms are likely to underlie the two processes, although there is evidence to suggest that the same brain region is involved in recognition of familiar stimuli in both filial and sexual imprinting. There is little evidence for a direct role of hormones in the learning process of imprinting. Androgen metabolism may be a factor constraining the development of a predisposition in the chick. Research into the neural mechanism of filial imprinting in the chick has revealed that a restricted part of the forebrain (IMHV) is likely to be a site of memory storage. Changes in synapse morphology and in the number of NMDA receptors have been found, limited to this region, and correlated with the strength of preference.     

Longevity Determined by Paternal Ancestors' Nutrition during Their Slow Growth Period

Social circumstances often impinge on later generations in a socio-economic manner, giving children an uneven start in life. Overfeeding and overeating might not be an exception. The pathways might be complex but one direct mechanism could be genomic imprinting and loss of imprinting. An intergenerational "feedforward" control loop has been proposed, that links grandparental nutrition with the grandchild's growth. The mechanism has been speculated to be a specific response, e.g. to their nutritional state, directly modifying the setting of the gametic imprint on one or more genes. This study raises the question: Can overnutrition during a child's slow growth period trigger such direct mechanisms and partly determine mortality? Data were collected by following-up a cohort born in 1905 in Överkalix parish, northernmost Sweden. The probands were characterised by their parents' or grandparents' access to food during their own slow growth period. Availability of food in the area was defined by referring to historical data on harvests and food prices, records of local community meetings and general historical facts. If there was a surfeit of food in the environment when the paternal grandfather was a 9–12 year old boy a shortening of the proband survival could be demonstrated. The influence of parents', maternal grandparents' and paternal grandmothers' access to food during their slow growth period was discounted in a multivariable analysis. The results are indicative of very early programming mechanisms in human adaptation to the social environment.     

Dynamics of a memory trace: effects of sleep on consolidation

BACKGROUND: There is evidence that sleep is important for memory consolidation, but the underlying neuronal changes are not well understood. We studied the effect of sleep modulation on memory and on neuronal activity in a memory system of the domestic chick brain after the learning process of imprinting. Neurons in this system become, through imprinting, selectively responsive to a training (imprinting) stimulus and so possess the properties of a memory trace. RESULTS: The proportion of neurons responsive to the training stimulus reaches a maximum the day after training. We demonstrate that sleep is necessary for this maximum to be achieved, that sleep stabilizes the initially unstable, selective responses of neurons to the imprinting stimulus, and that for sleep to be effective, it must occur during a particular period of time after training. During this period, there is a time-dependent increase in EEG activity in the 5-6 Hz band, that is, in the lower range of the theta bandwidth. The effects of sleep disturbance on consolidation cannot be attributed to fatigue or to stress. CONCLUSIONS: We establish that long-term trace consolidation requires sleep within a restricted period shortly after learning. Undisturbed sleep is necessary for the stabilization of long-term memory, measured at the behavioral and neuronal levels, and of long-term but not short-term neuronal responsiveness to the training stimulus.     

Effect of single neonatal treatment with the soy bean phytosteroid,genistein on the sexual behavior of adult rats

Hormonal imprinting develops during the perinatal critical period, when the target hormone meets the yet unmatured receptor. As a consequence of imprinting the receptor accomplishes its maturation reaching the binding capacity characteristic to adults. In this period in the presence of foreign molecules similar to the target hormone faulty imprinting may occur with life-long consequences. Soy bean contains phytosteroids which can mimic estrogen effects. In the present experiments single genistein (20 microg) or combined genistein + benzpyrene (20 microg) treatments were done neonatally and the sexual behavior of male and female adult animals was studied. Genistein significantly increased the lordosis quotient of females, which was compensated by neonatal benzpyrene treatment. Genistein also enhanced the sexual activity of males, and this was significantly not reduced by parallel benzpyrene treatment. The results show that neonatal genistein exposure can imprint sexual activity for life and the presence of a second imprinter can modify genistein's behavioral effect.     

Sexual imprinting on ecologically divergent traits leads to sexual isolation in sticklebacks

During sexual imprinting, offspring learn parental phenotypes and then select mates who are similar to their parents. Imprinting has been thought to contribute to the process of speciation in only a few rare cases; this is despite imprinting's potential to generate assortative mating and solve the problem of recombination in ecological speciation. If offspring imprint on parental traits under divergent selection, these traits will then be involved in both adaptation and mate preference. Such 'magic traits' easily generate sexual isolation and facilitate speciation. In this study, we show that imprinting occurs in two ecologically divergent stickleback species (benthics and limnetics: Gasterosteus spp.). Cross-fostered females preferred mates of their foster father's species. Furthermore, imprinting is essential for sexual isolation between species; isolation was reduced when females were raised without fathers. Daughters imprinted on father odour and colour during a critical period early in development. These traits have diverged between the species owing to differences in ecology. Therefore, we provide the first evidence that imprinting links ecological adaptation to sexual isolation between species. Our results suggest that imprinting may facilitate the evolution of sexual isolation during ecological speciation, may be especially important in cases of rapid diversification, and thus play an integral role in the generation of biodiversity.     

Experience-dependent transfer of Otx2 homeoprotein into the visual cortex activates postnatal plasticity

Neural circuits are shaped by experience in early postnatal life. Distinct GABAergic connections within visual cortex determine the timing of the critical period for rewiring ocular dominance to establish visual acuity. We find that maturation of the parvalbumin (PV)-cell network that controls plasticity onset is regulated by a selective re-expression of the embryonic Otx2 homeoprotein. Visual experience promoted the accumulation of non-cell-autonomous Otx2 in PV-cells, and cortical infusion of exogenous Otx2 accelerated both PV-cell development and critical period timing. Conversely, conditional removal of Otx2 from non-PV cells or from the visual pathway abolished plasticity. Thus, the experience-dependent transfer of a homeoprotein may establish the physiological milieu for postnatal plasticity of a neural circuit.     

Plasticity in the visual system: role of neurotrophins and electrical activity

We report recent results concerning the action of neurotrophins on the development and plasticity of the visual system of mammals and in particular of their visual cortex. It has been demonstrated that NGF prevents all the effects of monocular deprivation during the critical period. BDNF, that in part also prevents the effects of monocular deprivation, has the interesting additional property of accelerating the development of inhibitory processes. In transgenic mice overexpressing BDNF only in the cortex, the critical period for plasticity initiates a week earlier and presents a precocious closure. Visual acuity also develops much before than in normal animals. These phenomenological observations are paralleled by a precocious increase of inhibitory synapses and inhibitory currents in pyramidal neurons. LTP, tested by stimulation of the white matter, recording in layers 2 and 3 of the visual cortex, presents modifications correlated with the alterations observed in the critical period. Last we report the finding from in vitro and in vivo experiments that MAPkase (Erg 1 and 2) is the molecular chain of events driven both by light and neurotrophins, likely at the bases of the phenomena of plasticity observed during the critical period.     

Specific differentially methylated domain sequences direct the maintenance of methylation at imprinted genes

Landmark features of imprinted genes are differentially methylated domains (DMDs), in which one parental allele is methylated on CpG dinucleotides and the opposite allele is unmethylated. Genetic experiments in the mouse have shown that DMDs are required for the parent-specific expression of linked clusters of imprinted genes. To understand the mechanism whereby the differential methylation is established and maintained, we analyzed a series of transgenes containing DMD sequences and showed that imperfect tandem repeats from DMDs associated with the Snurf/Snrpn, Kcnq1, and Igf2r gene clusters govern transgene imprinting. For the Igf2r DMD the minimal imprinting signal is two unit copies of the tandem repeat. This imprinted transgene behaves identically to endogenous imprinted genes in Dnmt1o and Dnmt3L mutant mouse backgrounds. The primary function of the imprinting signal within the transgene DMD is to maintain, during embryogenesis and a critical period of genomic reprogramming, parent-specific DNA methylation states established in the germ line. This work advances our understanding of the imprinting mechanism by defining a genomic signal that dependably perpetuates an epigenetic state during postzygotic development.     

A precritical period for plasticity in visual cortex

One of the seminal discoveries in developmental neuroscience is that altering visual experience through monocular deprivation can alter both the physiological and the anatomical representation of the two eyes, called ocular dominance columns, in primary visual cortex. This rearrangement is restricted to a critical period that starts a few days or weeks after vision is established and ends before adulthood. In contrast to the original hypothesis proposed by Hubel and Wiesel, ocular dominance columns are already substantially formed before the onset of the critical period. Indeed, before the critical period there is a period of ocular dominance column formation during which there is robust spontaneous activity and visual experience. Recent findings raise important questions about whether activity guides ocular dominance column formation in this 'precritical period'. One developmental event that marks the passage from the precritical period to the critical period is the activation of a GABAergic circuit. How these events trigger the transition from the precritical to critical period is not known.     

Selective loss of imprinting in the placenta following preimplantation development in culture

Preimplantation development is a period of dynamic epigenetic change that begins with remodeling of egg and sperm genomes, and ends with implantation. During this time, parental-specific imprinting marks are maintained to direct appropriate imprinted gene expression. We previously demonstrated that H19 imprinting could be lost during preimplantation development under certain culture conditions. To define the lability of genomic imprints during this dynamic period and to determine whether loss of imprinting continues at later stages of development, imprinted gene expression and methylation were examined after in vitro preimplantation culture. Following culture in Whitten's medium, the normally silent paternal H19 allele was aberrantly expressed and undermethylated. However, only a subset of individual cultured blastocysts (approximately 65%) exhibited biallelic expression, while others maintained imprinted H19 expression. Loss of H19 imprinting persisted in mid-gestation conceptuses. Placental tissues displayed activation of the normally silent allele for H19, Ascl2, Snrpn, Peg3 and Xist while in the embryo proper imprinted expression for the most part was preserved. Loss of imprinted expression was associated with a decrease in methylation at the H19 and Snrpn imprinting control regions. These results indicate that tissues of trophectoderm origin are unable to restore genomic imprints and suggest that mechanisms that safeguard imprinting might be more robust in the embryo than in the placenta.     

The synaptic proteome during development and plasticity of the mouse visual cortex

During brain development, the neocortex shows periods of enhanced plasticity, which enables the acquisition of knowledge and skills that we use and build on in adult life. Key to persistent modifications of neuronal connectivity and plasticity of the neocortex are molecular changes occurring at the synapse. Here we used isobaric tag for relative and absolute quantification to measure levels of 467 synaptic proteins in a well-established model of plasticity in the mouse visual cortex and the regulation of its critical period. We found that inducing visual cortex plasticity by monocular deprivation during the critical period increased levels of kinases and proteins regulating the actin-cytoskeleton and endocytosis. Upon closure of the critical period with age, proteins associated with transmitter vesicle release and the tubulin- and septin-cytoskeletons increased, whereas actin-regulators decreased in line with augmented synapse stability and efficacy. Maintaining the visual cortex in a plastic state by dark rearing mice into adulthood only partially prevented these changes and increased levels of G-proteins and protein kinase A subunits. This suggests that in contrast to the general belief, dark rearing does not simply delay cortical development but may activate signaling pathways that specifically maintain or increase the plasticity potential of the visual cortex. Altogether, this study identified many novel candidate plasticity proteins and signaling pathways that mediate synaptic plasticity during critical developmental periods or restrict it in adulthood.