How long does plasticity occur in the brain

In , the Italian Neuropsychiatrist Eugenio Tanzi proposed that through specific learning or practice, repetitive activity in a neuronal pathway could produce hypertrophy, thereby reinforcing the already existing connections Berlucchi and Buchtel, Later on it was Tanzi's disciple Ernesto Lugaro who suggested the chemical nature of synaptic transmission, and who formulated the link between Tanzi's theories and Cajal's ideas of neurotropism in and Berlucchi and Buchtel, Thus, while it may remain unclear who first coined the term plasticity, the work of Cajal undoubtedly stimulated and influenced the first theories about synapses, synaptic transmission, and synaptic plasticity.

During the twentieth century, the question of how information is stored in the brain stimulated an enormous body of work that focused on the properties of synaptic transmission. Indeed, a year before the publication of Hebb's book, the Polish Neurophysiologist Konorski postulated that morphological changes in neural connections could be the substrate of learning Markram et al.

The first evidence linking short-term plasticity to behavioral modifications came from studies in Aplysia Kandel and Tauc, Short-term facilitation and synaptic depression that lasts from milliseconds to minutes can be elicited by different protocols, like paired-pulse stimulation or repetitive high-frequency stimulation Zucker and Regehr, Short-term plasticity is considered to be important in short-term responses to sensory inputs, transient modification of behavioral states, and short-term memory Citri and Malenka, These findings were obtained thanks to a key technical development that occurred in parallel in Andersen's laboratory: the use of the brain slice preparation Skrede and Westgaard, Indeed, research using the hippocampal slice preparation has continued to enhance our understanding of synaptic plasticity over the years.

Another form of long-term plasticity, long-term depression, or LTD, was first proposed in Lynch et al. These advances, along with the development of intracellular recordings in brain slices and patch-clamp techniques, led to the identification of different forms of short- and long-term plasticity at distinct synapses across the brain. For example, in the 80s NMDA receptors were shown to be involved in synaptic plasticity Herron et al. In the last decade of the twentieth century, the importance of the relative timing of action potentials generated by pre- and postsynaptic neurons at monosynaptic connections was shown when measured in pairs of cortical neurons Markram et al.

The elegance and simplicity of this experimental paradigm, also called spike-timing-dependent plasticity STDP , attracted the attention of the neuroscientific community. However, further studies into the rules governing STDP in different types of neurons and synapses revealed a much more complex landscape Markram et al.

Moreover, another form of persistent synaptic plasticity was suggested at that time, called metaplasticity Abraham and Bear, The role of metaplasticity is not yet clear but it may serve to maintain synapses within a dynamic range of activity, allowing synapses and networks to respond to a changing environment.

At the end of the twentieth century, a new form of plasticity that operates over longer time scales was discovered, called homeostatic plasticity Turrigiano et al. Homeostatic plasticity involves a number of phenomena that balance the changes in neural activity to maintain homeostasis over a wide range of temporal and spatial scales Turrigiano, The best studied example of homeostatic plasticity is known as synaptic scaling Turrigiano et al. The relationship between STDP and homeostatic plasticity is not well-understood and it is currently an interesting area of research Watt and Desai, In parallel with activity-dependent changes in synaptic strength and efficacy of synaptic transmission, structural modifications of axonal, dendritic branches, and spine morphology occurs, a phenomenon called structural synaptic plasticity.

In particular, different studies have correlated bidirectional structural spine changes with activity-dependent synaptic plasticity, i. Nowadays, in vivo two-photon imaging techniques combined with electrophysiological recordings are instrumental in order to clarify the relationship between functional-structural synaptic plasticity and behavior.

For example, spine formation has been observed following successful reaching task related with motor memories Xu et al. Furthermore, the discovery of STDP at the beginning of this century, generated interest in the influence of timing and frequency on the parameters required to induce synaptic plasticity Lisman and Spruston, , ; Markram et al.

This was in part because traditional forms of plasticity are provoked with protocols based on stimulation frequencies that are sometimes far from physiological, and they are therefore unlikely to occur in vivo. Thus, a key future challenge will be to determine the mechanisms, rules and roles of STDP in vivo Schulz, In this regard, it will be important to define the precise influence of neuromodulators on STDP Pawlak et al.

In addition, it will be necessary to develop a unitary mechanistic framework that simplifies and explains the tremendous variability in the properties of STDP in different brain regions and synapses. Finally, more detailed studies will be required to define the recently demonstrated role of glial cells in synaptic plasticity e. Synaptic plasticity is intrinsic to the development and function of the brain, and it is essential for learning and memory processes.

Thus, investigating how synaptic plasticity occurs and how it is modified during specific developmental time windows will provide key information as to how the brain develops. Furthermore, the translational relevance of animal studies of synaptic plasticity must be further clarified in the future. Studies in human tissue indicate that synaptic plasticity of human synapses is a candidate mechanism for learning and memory, although direct evidence of the actual cellular mechanism is lacking Mansvelder et al.

As observed in animal studies, activity-dependent, Hebbian-like synaptic changes can be induced in the human brain in vivo , although with differences in the specific plasticity rules Mansvelder et al. Current electrophysiological and imaging techniques commonly used in animal models can be used for in vitro experiments with human tissue from dissected patients.

However, a major challenge for the future is to study synaptic plasticity in the human brain in vivo. To this end, non-invasive techniques like transcranial magnetic stimulation TMS may represent a step forward Polania et al. On a different note, plasticity is also a phenomenon that aids brain recovery after the damage produced by events like stroke or traumatic injury.

Indeed, the ability to manipulate specific neuronal pathways and synapses has important implications for therapeutic and clinical interventions that will improve our health.

Promising therapies like deep brain stimulation, non-invasive brain stimulation, neuropharmacology, exercise, cognitive training, or feedback using real-time functional magnetic resonance Cramer et al. A better understanding of the mechanisms governing neuroplasticity after brain damage or nerve lesion would help improve patient's quality of life, eventually saving costs to National Health Systems worldwide.

Therefore, the study of synaptic plasticity has clear consequences that reach beyond the research environment. Increasing our understanding of how learning and memory processes are modified during development, and of how the brain modifies its activity and recovers after damage, should be considered in some depth by policy makers.

In the light of the above, such efforts are likely to provide social benefits in the spheres of Healthcare and Education, thereby aiding long-term socio-economic planning. All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Abraham, W. Metaplasticity: the plasticity of synaptic plasticity. Trends Neurosci. Abrahamsson, T. Differential regulation of evoked and spontaneous release by presynaptic NMDA receptors. Neuron 96, — Allen, N. Glia as architects of central nervous system formation and function. Science , — Andrade-Talavera, Y.

Presynaptic spike timing-dependent long-term depression in the mouse hippocampus. Cortex 26, — Berlucchi, G. Neuroplasticity — or brain plasticity — is the ability of the brain to modify its connections or re-wire itself. Without this ability, any brain, not just the human brain, would be unable to develop from infancy through to adulthood or recover from brain injury.

What makes the brain special is that, unlike a computer, it processes sensory and motor signals in parallel. The problem becomes severe when errors in development are large, such as the effects of the Zika virus on brain development in the womb, or as a result of damage from a blow to the head or following a stroke. Yet, even in these examples, given the right conditions the brain can overcome adversity so that some function is recovered. This is something that is predetermined by your genes.

For example, there is an area of the brain that is devoted to movement of the right arm. Damage to this part of the brain will impair movement of the right arm. In other words, neuroplasticity is not synonymous with the brain being infinitely malleable. In a study of Caenorhabditis elegans , a type of nematode used as a model organism in research , it was found that losing the sense of touch enhanced the sense of smell.

This suggests that losing one sense rewires others. As in the developing infant, the key to developing new connections is environmental enrichment that relies on sensory visual, auditory, tactile, smell and motor stimuli. However, another part of this development depends on neuroplasticity. As a child grows, the incoming information from light sources, such as light reflected off the faces of caregivers, provides necessary cues for the brain to adjust its growth patterns.

The equivalent plasticity-based growth also occurs with the other senses, calibrating the young person to local conditions. The development of language reveals even more about neuroplasticity. Again, part of this functionality is genetically hardwired, but part depends on feedback from the environment. An individual has certain nerve cells programmed to become grammar modules.

For these to function correctly, they require the input of specific grammatical rules from a culture, such as the rules of English or Spanish.

Thus, neuroplasticity enables the brain to process language. New neural connections, different densities of nerve cells, varying strengths of neural connections. How does neuroplasticity work? At the most basic level, it starts with the production of a new nerve cell neurogenesis.

Then, individual neurons develop new connections to each other. A neuron works by sending or receiving electrochemical signals with other neurons in the brain. The way that individual neurons connect to each other controls how the signals get sent, like the routing of messages over the internet or of instructions codes in a computer processor.

As each neuron develops connections to others, this results in growing clusters of cells. The neurons can adjust the level or strength of signal with connecting neurons. This ongoing process provides fine-tuning of the neural architecture.

Rewiring larger regions, reorganizing the nervous system at multiple levels. Neurons work together at several different levels. Not only individual cells, but even clumps within brain regions can grow in greater or lower density. As cells grow or die in different regions, the relative densities vary. Such variations can provide an even broader adjustment or neuroplasticity in the brain than individual nerve cell connections.

When nerve bundles become broken, through injury or surgery, the brain can regrow these elements Doidge, Surprisingly, the brain can reconnect itself in an efficient manner even to deal with sizable upsets. It operates like a plant, able to regrow around lost parts. Gradually, the repairs extend through subcortical layers, reaching larger-scale cortical levels of the brain. This growth occurs throughout the nervous system, including the spine and distributed branches, not only in the brain.

Recurring synaptic connections grow more efficient cell assembly theory. The nerve connections grow stronger when one cell fires before the other, rather than when they both fire simultaneously.

Sequential firing produces a causal relationship, enabling the nervous system to learn. As a comparison, internet search engines track which sites link directly to which other sites. The combined directional links of billions of sites produce an efficient map of the internet, as the combined directional links of billions of neurons produce an efficient map of the body and its environment. The famous study by Maguire et al. She studied 16 London taxi drivers and found an increase of the volume of grey matter in the posterior hippocampus compared to a control group.

This area of the brain is involved in short-term memory and spatial navigation. Further support comes from Mechelli et al who found that learning a second language increases the density of grey matter in the left inferior parietal cortex and that the degree of structural reorganization in this area is influenced by the fluency attained and the age at which the second language was learnt.

With age, neuroplasticity decreases however Mahncke et al. This has potential benefits for society as a brain-plasticity-based intervention targeting normal age-related cognitive decline may delay the time when these people need support in their everyday life. Learning and new experiences cause new neural pathways to strengthen whereas neural pathways which are used infrequently become weak and eventually die.

Thus brains adapt to changing environments and experiences. Thus, the complex cognitive demands involved in mastering video games caused the formation of new synaptic connections in brain sites controlling spatial navigation, planning, decision-making, etc. Davidson matched 8 experienced practitioners of Tibetan Buddhist meditation against 10 participants with no meditation experience.

Levels of gamma brain waves were far higher in the experienced meditation group both before and during meditation. Gamma waves are associated with the coordination of neural activity in the brain.

This implies that meditation can increase brain plasticity and cause permanent and positive changes to the brain. Kempermann found that rats housed in more complex environments showed an increase in neurons compared to a control group living in simple cages.

Changes were particularly clear in the hippocampus — associated with memory and spatial navigation. A similar phenomenon was shown in a study of London taxi drivers. MRI scans revealed that the posterior portion of the hippocampus was significantly larger than a control group, and the size of difference was positively correlated with the amount of time spent as a taxi driver i.

Neuroplasticity can explain a broad range of facts about the structure and function of the brain. This notion does, however, have some constraints.

These involve the gradual decline of neuroplasticity with age, as well as certain restrictions in terms of how much neural plasticity is possible even in young, healthy people. Also, scientists have yet to learn many critical aspects about neuroplasticity. The limits of brain plasticity decline with age, biological constraints. Neuroplasticity can only go so far. Non-human animals show many areas of brain plasticity. However, their brains cannot reshape themselves enough to learn a human language or perform advanced mathematics.

Neuroplasticity works on biologically available material, which imposes limitations like only adjusting the specific neural substrate of a cognitive function, or adapting a brain function somewhat for a season.

In people whose brains reuse large regions for different operations, such as blind people whose vision centers become useful for touch or sound, this capacity can only work for specific types of processing.

Even people blind from birth would not become able to reuse their color-detection brain cells for touch, because unlike geometry-detection brain cells, these have hard-coding for visual input Grafman, Even in healthy individuals, neuroplasticity declines with age Lu et al. Over the years, as the body becomes less flexible, so does the brain. Much of neuroplasticity is geared towards enabling younger people to develop an understanding and capacity to act within their surroundings.

This stabilizes to some extent in adulthood, even declining in the elderly. One can see the decline of neuroplasticity in how older people become more fixed in their ways, while younger people learn rapidly. Neuroplasticity has grown over recent centuries into a topic of considerable interest to scientists, but remains poorly understood. The brain imaging tools for conducting studies on this topic are still young.

As such, much knowledge has yet to be found. Scientists remain unsure about many of the mechanisms underlying brain plasticity Grafman, While a few of the processes have been studied in molecular detail, others have not, and the conceptual understanding of how they take place is a source of ignorance. The technical underpinnings of neuroplasticity therefore represent an area of active interest, in which further investigations are being carried out.