Developmental plasticity

The underlying principle of synaptic plasticity is that synapses undergo an activity-dependent and selective strengthening or weakening so that new information can be stored.[4][5] Synaptic plasticity depends on numerous factors including the threshold of the presynaptic stimulus in addition to the relative concentrations of neurotransmitter molecules. Synaptic plasticity has long been implicated for its role in memory storage and is thought to play a key role in learning.[6][5] However, during developmental periods, synaptic plasticity is of particular importance, as changes in the network of synaptic connections can ultimately lead to changes in developmental milestones. For instance, the initial overproduction of synapses during development is key to plasticity that occurs in the visual and auditory cortices.[7] In experiments conducted by Hubel and Wiesel, the visual cortex of kittens exhibits synaptic plasticity in the refinement of neural connections following visual inputs. Correspondingly, in the absence of such inputs during development, the visual field fails to develop properly and can lead to abnormal structures and behavior.[8] Furthermore, research suggests that this initial overproduction of synapses during developmental periods provides the foundation by which many synaptic connections can be formed, thus resulting in more synaptic plasticity. In the same way that synapses are abundant during development, there are also refining mechanisms that assist in the maturation of synapses in neural circuits. This regulatory process allows the strengthening of important or frequently used synaptic connections while reducing the amount of weak connections.[9]

In order to maintain balance, homeostatic controls exist to regulate the overall activity of neural circuits, specifically by regulating the destabilizing effects of developmental and learning processes that result in changes of synaptic strength. Homeostatic plasticity also helps regulate prolonged excitatory responses, which lead to a reduction in all of a neuron's synaptic responses.[10] Numerous pathways have recently been associated with homeostatic plasticity, though there is still no clear molecular mechanism. Synaptic scaling is one method that serves as a type of autoregulation, as neurons can recognize their own firing rates and notice when there are alterations; calcium-dependent signals control the levels of glutamate receptors at synaptic sites in response. Homeostatic mechanisms may be local or network-wide.[11]

While synaptic plasticity is considered to be a by-product of learning, learning involves interaction with the environment to acquire the new information or behavior; synaptic plasticity merely represents the change in strength or configuration of neural circuits.[12] Learning is crucial, as there is considerable interaction with the environment, which is when the potential for acquiring new information is greatest. By depending largely upon selective experiences, neural connections are altered and strengthened in a manner that is unique to those experiences.[13] Experimentally, this can be seen when rats are raised in an environment that allows ample social interaction, resulting in increased brain weight and cortical thickness. In contrast, the inverse is seen following rearing in an environment devoid of interaction.[14] Also, learning plays a considerable role in the selective acquisition of information and is markedly demonstrated when children develop one language instead of another. Another example of such experience-dependent plasticity that is critical during development is the occurrence of imprinting. This occurs as a result of a young child or animal being exposed to a novel stimulus and rapidly implementing a certain behavior in response.[15]

Initial stages of neural development begin early on in the fetus with spontaneous firing of the developing neuron.[19] These early connections are weak and often overlap at the terminal ends of the arbors.[20] The young neurons have complete potential of changing morphology during a time span classified as the critical period to achieve strengthened and refined synaptic connections. It is during this time that damaged neuronal connections can become functionally recovered. Large alterations in length and location of these neurons can occur until synaptic circuitry is further defined.[21] Although organization of neural connections begins at the earliest stages of development, activity-driven refinement only begins at birth when the individual neurons can be recognized as separate entities and start to enhance in specificity.[22] The gradual pruning of the initially blurry axonal branching occurs via competitive and facilitative mechanisms, relying on electrical activity at the synapses; axons that fire independently of each other tend to compete for territory, whereas axons that synchronously fire mutually amplify connections.[23] Until this architecture has been established, retinal focus remains diffuse. Perpetuation of these newly formed connections or the lack thereof depends on maintenance of electrical activities at the synapses. Upon refinement, the elaborate connections narrow and strengthen to fire only in response to specific stimuli to optimize visual acuity.[24] These mechanisms can malfunction with the introduction of toxins, which bind to sodium channels and suppress action potentials and consequently electrical activity between synapses.[25]

Quantification of synaptic networks has primarily been through retinal wave detection using Ca²⁺ fluorescent indicators. Prior to birth, retinal waves are seen to originate as clusters that propagate through the refractory region. These assays have been shown to provide spatiotemporal data on the random bursts of action potentials produced in a refractory period.[26] Another assay recently developed to assess the depth of neuronal connections utilizes the trans-neuronal spread of rabies.[27] This method of tracing employs the migration of a neurotropic virus through tightly interconnected neurons and specific site labeling of distinct connections.[28] Patch-clamping experiments and calcium imaging are often conducted based on preliminary results from this assay in order to detect spontaneous neuronal activity.[29] A method for in vitro synaptic quantification has been developed that uses immunofluorescence to measure synaptic density in different cell cultures.[30]

Graphical representation of a reaction norm, which determines distribution of potential phenotypes.

The norm of reaction, or reaction norm, is a pattern of phenotypic plasticity that describes how a single genotype can produce an array of different phenotypes in response to different environmental conditions.[2] Furthermore, a reaction norm can be a graphical representation of organismal variation in phenotype in response to numerous environmental circumstances. The graphical representation of reaction norms is commonly parabolic in shape, which represents the variation in plasticity across a population.[36] Additionally, reaction norms allow organisms to evaluate the need for various phenotypes in response to the magnitude of the environmental signal.[2]

Example of phenotypic plasticity in the desert locust Schistocerca gregaria. The green pigment locust (top) has miniature wings that result from a low-density population. The deep pigmentation locust (bottom) has leg and wing development suitable for migration, which arose due to a high-density environment.[2]

Polyphenism refers to the ability of a single genotype to produce a variety of phenotypes in response to different environmental conditions. In contrast to reaction norms, which produce a continuous range of phenotypes, polyphenisms allow a distinct phenotype to arise from altering environmental conditions.[37] An example of polyphenism can be seen in the Florida carpenter ant, Camponotus floridanus. For a developing ant embryo, a multitude of environmental signals can ultimately determine the adult ant morphology. For Florida carpenter ants, the end phenotype and behavior are determined by the morphology; developing ants can either become minor workers, major workers, or queen ants. Although the polyphenism of the ants has been documented, research is still needed to determine the molecular mechanisms for the induction of each unique phenotype.[38]

Environmental cues in either the maternal or the embryonic environment can result in changes in the embryo. Embryonic development is a sensitive process and can be impacted by cues from predators,[39] light,[40] and/or temperature.[41] For example, in Daphnia, neonates exposed to predator cues displayed higher expression of genes related to digestion, reproductive function, and defense. It was hypothesized that this increase in gene expression would allow the Daphnia to defend themselves and that an increase in growth would result in a larger investment in future offspring. Subsequent generations exhibited a similar pattern, despite not being exposed to any predator cues, suggesting an inheritance of epigenetic expression factors.[39] An organism's sensitivity to light during development could be useful in predicting what phenotype may be the most beneficial in the future based on the foliage of the mature organism.[40] Several species, including alligators and tortoises, have temperature-dependent sex determination, where the sex of the organism is dependent on the environmental temperature during a crucial thermosensitive period. An active area of research involves the mechanisms of temperature sex determination, which have been hypothesized to be associated with the methylation of specific genes.[41]