Education Learning and the Mind Cognitiv

  EDUCATION, LEARNING AND THE

MIND: COGNITIVE

  The Framing Document for the Presentation E glish as The ap Deli e ed “epte e to the 2015 NeuroELT Brain Days International

  Conference, Kyoto, Japan

  The neuroscience of learning and the role of language in cognition – neuroscience in the classroom: The power of English as a medium for learning and cognitive development in an ELT * environment

  CNE COGN ITIVE N EUROED UCATION

English as Therapy

• *ELT (English Language Teaching) refers to the teaching of English to non-native English _{speakers as a foreign, or second, language (TEFL in t}

  he lea e s ati e ou t , o TESL in _{an English-speaking country, respectively).} A P r esentation to the 2015 Neur oELT Br ain

   Days

  Inter national Confer ence Kyoto, J apan September 27 by Dr. Spencer M. Robinson

  Research Associate ^Director

National Institute for Str oke Center for Applied Social

And Applied Neur osciences

  Neur oscience (CASN)

AUT Univer sity Fukui, J apan

Auckland, New Zealand

INTRODUCTION

  This presentation introduces CNE (Cognitive Neuroeducation), a new, noninvasive, nonpharmacological modality for intervention in cognitive and behavioral disorder with the promise of full recovery therefrom.

  As will be demonstrated in this presentation, cognition, behavior and learning may be understood as essentially interdependent terms referring to the basic interlocked mechanisms of the human social brain, and therefore CNE may be defined as a program or curriculum for optimizing positive learning outcomes that enhance cognition in the formation of well- attuned, socially integrated, self-actualizing and confident, independent behavior.

  This presentation is geared to the TEFL (teaching of English as a foreign language) community in Japan, and as such, will be more language orientated (especially English teaching oriented) than behaviorally orientated; however, the theory, principles and basic structure of CNE as presented herein, are equally valid and effective for both orientations, irrespective of country or native language of the participants.

  CNE is unique in that it is the only modality in the fields of learning and mental health that is strictly

tied to how the brain actually works within a tightly

constructed, exhaustively comprehensive model of the mind as formed exclusively from rigorous evidence-based analysis.

  To explain CNE, its theories and principles, it is first necessary to outline a model of human behavior

based on the evolution of the human brain and the

unique relationship between the human brain and human behavior in comparison with behavioral formation in all other taxa. To explore this relationship we begin by introducing some initial definitions.

  

Some Initial Definitions:

• The te hu a ill e used herein to refer exclusively to the anatomically modern human (AMH), identified by the trinomial Homo

  sapiens sapiens, constituting the genus, species, and subspecies of the taxon.

• Taxon = A single designated type of organism that constitutes a distinctive identity within the system of organism classification, such as

  

Homo sapiens sapiens. The plural of taxon is

taxa.

• Trinomial = The identification of an organism by designated genus + species + subspecies.
• Binomial = The identification of an organism by designated genus + species.
• Genotype = The genetic makeup (as distinguished from physical appearance) of an organism encoded by the combination of alleles on individual chromosomes, a particular combination determining a specific trait.

• Allele = One member of a pair (or any of the series) of genes occupying a specific spot on a chromosome (called locus) that controls the same trait.
• Phenotype = The composite of an organism's observable characteristics or traits, such as its morphology, development, biochemical or physiological properties, phenology, behavior, and products of behavior
• – the physical and behavioral expression of a o ga is s ge eti makeup dependent upon which genes are dominant and on the interaction between genes and environment.

• Phenology = The response to the relationship between season and climate in the cycles of plant and animal life such as flowering, breeding, migration, etc.
• Operant behavior, as defined herein, refers to human voluntary, incidentally learned, internally driven behavioral reactions as opposed to

  involuntary, externally coerced and purposefully

  manipulated conditioned responses, and thus as used herein does not exactly align with the ea i g of ope a t as used i the “ki e ia o ept of ope a t o ditio i g. U less otherwise indicated, all references to human behavior herein pertain exclusively to operant

• Phylogeny = the evolutionary branching process by which organisms evolve through differentiation into groups of immediate and more distant relationships, each group distinguished by a unique combination of morphological and behavioral features.
• Clade = a distinct phylogenetic branch, from living or most recent genus or genera back through a clear, direct lineage to the single, earliest ancestral binomial form
• – a taxonomic group of organisms classified together on the basis of homologous features traced to a common ancestor.
• The human clade, as defined herein, constitutes the subtribe Hominina, consisting of the single

  genus of Homo, whose ancestral forms have been

  purported to include H. habilis, H. rudolfensis, H.

  ergaster, H. erectus, H. heidelbergensis, H. neanderthalensis, archaic H. sapiens and H. sapiens idaltu, to name some of the more prominent fossil discoveries. A number of fossil genera in the subtribe of Australopithecina have been suggested to be ancestral to the human clade, such as Australopithecus, Paranthropus, Ardipithecus, Sahelanthopus, Orrorin, and Kenyanthropus, but there is no definitive argument on the classification of many of the fossil forms and the composition of the human clade. Homo sapiens sapiens is the single extant

  

The tribe Hominini consists of the three subtribes , consisting of the single genus Pan; and , which consists of several extinct genera.

  Scienation

  : Kingdom

   Hominina

  Homo Class: be Panina

• Phylum:

  Order: Primates

• Pan

  thecina

  Suborder:

• †

  Family:

• †

  Subfamily: Homininae thropus

• †

  Tribe: Hominini

• †

  

• †

  Kenyanthropus

• †

   Subfamily ^HOMININAE Tribe HOMININI GORILLINI Subtribe Hominina Panina Australopithecina Genus Homo Pan * Paranthropus Gorilla _{Australopithecus} Sahelanthropus _Orrorin Ardipithecus _{Kenyanthropus}

• Consisting of two species of chimpanzee

  The Social Brain:

  A Unique Evolutionary Development of the Anatomically Modern Human (AMH)

• Many animal forms share some common characteristics, and taxa grouped in the same superfamily, family, subfamily, tribe, and genus, respectively, share closer and closer characteristics. What is critical in understanding human behavior in the achievement of balanced and optimum functioning within the unique conditions of human life, is to clearly define the essence as opposed to the details of that uniqueness. Bearing in mind that many taxa share many basic characteristics, the quality and degree of different properties varies dramatically across taxa, forming quite different modes by which distinct taxa
• While many taxa are behaviorally oriented toward a community or social structure, with biologically hardwired, preprogrammed role- specific differentiation such as in ant and wasp colonies and bee hives, or by a general rudimentary cognitive tendency toward forming small social hierarchical groups, such as in

  chimpanzee or gorilla groups, only one taxon has

  evolved a unique social brain inherently biologically encoded in the self-construction of the cognitive configuration and interpretation of self and individual experience within the framework of defined social roles and the construction of complex layers of social

  organization. That taxon is Homo sapiens sapiens,

  distinguished from all other taxa by its unique

  

Evolutionary Path of Social Brain:

  From Fixed Action Patterns to Pseudo-Fixed Action Patterns and Learned Response

• H. sapiens sapiens (AMH), distinct from all other extant animal taxa, is not biologically preprogrammed for specialized physiological and behavioral adaptation to a discrete habitat.
• Other taxa vs. AMH: Fixed action patterns (also known as innate releasing mechanisms or modal action patterns, and commonly referred to as i sti ts s. AMH pseudo-fixed action patterns and learned responses through socialization, reasoning, curiosity, creativity and invention.

Pseudo-Fixed Action Patterns

• Acute stress response (fight-or-flight response), attachment/bonding response, mating response, tend-and-befriend response, etc.
• Central mechanism of basic behavioral propensities = affective properties embedded within pseudo-fixed action patterns; e.g., fear, anger, rage, hate and violence in the acute stress response; love, compassion, empathy, concern, and selfless, protective loyalty in the attachment/bonding response and the tend- and befriend response, etc.

Learned vs. Preprogrammed Behavior

• Unlike hardwired automated mechanisms of fixed action patterns, human pseudo-fixed action patterns may be overridden by learning/experience and are mediated by individual genotype and phenotype and affective profile.
• While the predisposition of affect is an innate biological determinant of human behavior, the individual capacity for, and/or particular nature of, affective reaction is mediated by genotype and phenotype to the extent that each individual possesses a unique basic

• As well as an inextricable component of experience [i.e. the perception of ideas/images associated with the particular objectifications (concrete or abstract) of discrete types or classifications of external stimuli], individual affective reaction is highly malleable, and is modified or learned through experience.
• Because, normatively, all human reaction to external stimuli contains an affective component to greater or lesser degree (no matter how subtle), in the context of operant behavior the affective aspect of experience may place a positive or negative cast on any experience, and in highly emotive reactions, can completely override rational constructions of cause-and-effect relationships or logical connections in the learning process. Affective state plays a pivotal role in shaping how and what we learn, and, consequently, how we understand our world and react to it.

• The pseudo-fixed action pattern of curiosity, or inquisitiveness, is the driving force of exploration,

  imagination, discovery and invention necessary

  for adaptation to different habitats by obtaining

  knowledge about, and making innovative use of,

  natural resources in the manipulation of the environment to meet basic human needs.
• Because we are not physically fine-tuned to any particular habitat, we have to manipulate our

  environment to maintain our lives. By creatively

  transforming natural resources into shelter, clothing and tools for hunting, fishing, food

  gathering and food preparation and for defense

  against predators and foes, we are able to sustain

• Curiosity, or inquisitiveness, as a vehicle of adaptation, is consequently the major vehicle of learning. Curiosity, or inquisitiveness, an innate, essential and powerful motivator of human behavior, may be seen as a major driving force in all normative, operant human behavior.
• Through curiosity and imagination, this innate behavioral orientation toward discovery and adaptation has enabled humans to survive in a

  variety of habitats without being restricted to any

  single narrowly defined habitat or ecosystem,

  and, with the capacity to learn an endless variety

  of adaptive strategies, has enabled humans

• – by exploitation of all available resources and the flexibility to adjust to environmental changes
• – to successfully compete with animals that though much more biologically attuned to any specific

  habitat, are nevertheless restricted to rigidly fixed

  adaptations and thereby are highly vulnerable to

• Evolution is driven by the survival of the species, and in human evolution particular propensities and capacities in the biological makeup of the individual through the diversity of genotype and phenotype are essential for evolutionary survival in the maintenance of the widest possible range of adaptive strategies and the most heterogeneous gene pool for the greatest effective evolutionary selection.

• Through a highly diverse gene pool, the human phenotype extends over a vast range of potential individual behavioral and affective profiles.

• • Individual propensities uniquely mediate the way

  in which an individual responds to either basic needs or external stimuli, so that, while all humans share basic biologically innate predispositions of both perception and action, each individual possesses a distinct genotype and phenotype that uniquely shapes intricate ha a te isti st les o fla o s of pe eptio and action.

• Different propensities for behavior and different experiences lead to different individual interests, aptitudes and orientations and attractions in life, which lead to divisions of labor, skill specialization and role playing in a group structure constituting the foundations of society.
• Insufficiently equipped to compete with other animal taxa for survival on an individual basis, humans evolved to rely on the competitive edge of cooperative behavior in groups.

  

Cooperation:

The Key to Human Survival

• By cooperative behavior facilitated by language (particularly verbal communication), which led to both higher-order reasoning and tool-making flexibility to manipulate their environment, humans were able to out- strategize, out-plan, out-maneuver, and simply out-think their taxonomic rivals for survival.
• Human groups also competed with each other for survival in a particular habitat or region, so that social cohesiveness, role and skill diversification and skill expertise within a group leading to more specialized supportive social structures became the keys to group survival that pushed evolutionary determinants toward the human tendency for more sophisticated, intricate and complex social organization.

• So- alled o alit e ol ed as a o ditio of g oup survivability.
• Such so- alled hu a i tues as ou age, lo e, compassion, forgiveness, charity, mercy, consideration, honesty, honor, selflessness, steadfastness, loyalty, self- sacrifice, etc., are not simply moral codes of religious convictions or social ideals, but, like reason and rationality, are natural tendencies embedded within the pseudo-fixed

  action patterns and cognitive constructions of the human

  social brain that are designed to solidify group cohesiveness and effectiveness in maximization of the competiveness of a group
• – the greater these qualities among its members the stronger the group; conversely, the degree to which they are lacking among the members of a group (be it a mating pair, a family, a band, etc.), the less a group is able to work together effectively and benefit from the interrelationships of its members.
• For basic survival, 1) learning became the central operating principle of the human social brain;

  2) curiosity or inquisitiveness in response to novelty became the driving force of learning, 3) logic and reason became the principle method of understanding, 4) and affective state became the mechanism arbitrating the balance between understanding and action.

Formation of the Human Social Brain

• The advantages of cooperative behavior could only be effectively realized through the development of the community structure.
• Human evolution became increasingly orientated toward social behavior and the social brain through which the neurophysiology of an acute social consciousness began to emerge.

Behavioral Precepts of the Social Brain

  The social brain developed as a neurophysiological system driving a behavioral tendency toward the construction and maintenance of community structures consisting of complex, intricate social interactions within multilayered strata of differentially organized social formations, each defined by specific rules of conduct, constructs of meaning and prevailing frames of reference in entities evolving from such units as family, dyad, group, and to such constructions as tribes, ethnicities, religions and cultures and the development of superstructures such as city, state, nation, and civilization.

Human Experience as Social Phenomena

  Since the social brain, and therefore, the mind (the mind herein defined as a quality or abstraction derived from the sum total of the effects of the interlocking mechanisms within the brain) is organized in terms of patterned conceptualizations of social formations, it follows then, that all experience of the world, and, consequently, all learning, is interpreted, shaped, and internalized through an overarching social framework.

  Learning:

The Central Operating Principle of the

Social Brain

• Since all learning is acquired through experience, that is, by information from the world around us incidentally gathered through the unfolding of life in a society, and through the experience of learning a subject or trade intentionally studied as a selective response to o e s u i ue phe ot pe a d the options of o e s i u sta es, e a defi e lea i g as experience and experience as learning.

• • Experience is defined herein as the process of the

  differential recognition and registration of all sensory or extrasensory stimuli

• – that which one

  sees, hears, feels, smells, tastes or thinks about,

  consciously or subliminally (e.g., dreams).

• • Since we are not prewired for explicit behavior in

  a fixed habitat, but rather learn complex rules of behavior adaptable to any livable habitat and the myriad social contexts that may be formed in response to the conditions of any particular livable habitat; learning may be seen then as the central operating principle of the social brain acquired for evolutionary survival.

Learning as Social Interaction

  Everything we learn takes place in a social context. From birth and throughout our lives, our interactions with others shape our understanding of the world. Learning occurs as parents talk with their children, as children play together, and as teachers instruct and assist students. Though learning progresses through biologically determined stages, it is the social environments that determine how and what we learn.

  Learning as Socialization and Development

• • Learning takes place through our interactions and

  communication with others. Even as we sit reading a novel by ourselves we interact with the author, the social and cultural context of the

  novel and in thinking about the story within the

  context of our own situation and social values.
• Learning and development take place in the

  interactions children have with peers as well as

  with teachers and other adults. These social interactions develop language
• – which supports thinking
• – and they provide feedback and assistance that support ongoing learning. In a variety of ways these social interactions form the

  basis of the understandings that are internalized

  in the individual as cognitive constructs or schemata.

• A cognitive construct is defined herein as an i di idual s u i ue o ga izatio of the total set of patterns, relationships, associations, connections, impressions and feelings, interpretations and conceptual syntheses and implications that is internalized and encoded in the mind as a reaction to each discrete experience and which influences the perception and understanding of new experience.

• The cognitive schemata is defined herein as the complete set of cognitive constructs and all the intertwining interactions between them unique to each individual as encoded through the i di idual s life e pe ie es.
• The te su li i al is defi ed he ei as a cognitive condition operating below the threshold of, and inaccessible to, articulate awareness; i.e., a level of cognitive processing inaccessible to a conscious attention.

Components of Learning

  Learning represents everything that we have experienced and the way we have internalized the experiences, constituting all the knowledge and skills that we have gained, all the impressions of the events of our life that we have stored and are able to recall, and all the different feelings and ideas that we have about the world and the people we know and everything that we can imagine.

• From this understanding of learning we can say that learning, knowledge, understanding, memory, thinking, and our attitudes about life and the world are all different perspectives of the same phenomenon.
• The equation of what defines each of us as a unique individual, a distinct personality, the sum total of who each of us is, may then be understood as genotype + phenotype + learning = self.

  

Genotype and Phenotype vs. Behavior

Human phenotype is not a static condition but an

ongoing dynamic of the effects of environment (i.e.,

experience) on genetic expression. Though innate biological propensities of unique genotype and phenotype lead to basic highly individualistic st les o fla o s of i di idual pe eptio a d action, the built-in malleability of the human social brain, as a fundamental product of human evolution, may override such basic phenotypical behavioral characteristics to the extent that other, even very different, behavioral styles of social interaction are internalized to either more readily

accommodate or block out social communication in

reaction to the prevailing social context.

The Mechanism of Learning

• Both sense-given impressions of external stimuli and self-generated stimuli from the internal

  reconfiguration of impressions form distinctive

  patterns of neuronal interconnectivity in the brain representing basic subliminal conceptualizations by which thought frameworks are molded and experiences are cognitively codified.
• This process entails the systematization of the collection of internalizations of reactions to all the disti t sti uli that o stitute a i di idual s total experience in the formation of a fundamental conceptual schemata at the subliminal level of understanding.

• From the internalized collection and systematization of the aggregate of the immediate reactions to distinct stimuli, patterns of relationships are constructed (i.e., cognitive conceptualizations of experience are formed). This process is known as appe eptio .

  

Apperception

• Apperception refers to the mechanism by which new experience is assimilated into, and transformed by, the residuum of past experience of the individual to form a new whole.
• In apperception new experience is understood or interpreted through the lens of previous experience and the perspective formed from that previous experience, but also the new experience, however transformed, becomes part of the aggregate of experience of the individual and adds new information to the aggregate, thereby altering perspective, by which the new experience transforms the esiduu of the i di idual s life e pe ie e; the new experience being both transformed and transforming.

  

Neuroplasticity

• Neuroplasticity is the principal neurophysiological mechanism of the human brain through which apperception occurs.
• In the context of learning as the mechanism that drives human cognitive construction, neuroplasticity is defined as the biologically inherent and ongoing process of macrostructural changes in the human brain that occur throughout life as a result of 1) normal brain maturation in prenatal and postnatal development and later cycles of exuberant synaptogenesis and synaptic pruning; and 2) the subsequent effect of everyday sensory and extrasensory stimuli as shaped by environmental influences and apperception, exclusive

  of neurodevelopmental disorders and tissue

  degradation due to lesions, pathological processes of progressive neurodegeneration (including the neuronal

• In the context of learning and apperception as the mechanisms that drive human cognitive construction, neuroplasticity may be fundamentally understood as constantly changing patterns of neuronal interconnectivity involving the modulation of neuronal potentiation (activation readiness and firing strength), which largely consists of the processes of: 1) synaptic blooming and pruning, and 2) synaptic strength modulation.
• Synaptic strength is modulated by a multitude of conditions including presynaptic neuronal activation readiness and firing strength; neuromodulator influence (modulatory input-dependent plasticity); heterosynaptic plasticity that may involve the timing and strength of the firing of neighboring neurons or the timing relationship between pre- and postsynaptic neuronal pair firing (including STDP
• – spike timing dependent plasticity); synaptic scaling; and various
The Neuron and Chemical Synapse Structures in the Human Brain

  Chemical Synapse

• The synaptic blooming and pruning process

  

consists of synaptogenesis (the formation of new

synapses) and synaptic pruning (the elimination of redundant synapses). Both synaptogenesis (i.e., synaptic blooming) and synaptic pruning o all o u th oughout a i di idual s life, but at two important junctures there is an

explosion of both synaptic blooming and pruning

(exuberant synaptogenesis followed by extensive

elimination of excess synapses) necessary as an inherent part of the process of human brain development. These junctures are early childhood and again in early adolescence (the exact ages highly variable between individuals and different parts of the brain).

• Synaptic blooming and pruning is the process

  by which new synapses are generated in the brain and selected synapses eliminated to allow neurons to 1) strengthen or weaken existing connections, and 2) make new connections with other neurons in either modifying or forming new or more extensive or complex patterns of neuronal interconnections.

• The ongoing process of synaptic blooming and

  pruning maintains a regulated homeostasis through a basic overall synaptic quantity in the

brain (although there is some evidence that there

is a natural, gradual loss of synaptic quantity throughout later adulthood), and fine-tunes neuronal networks by eliminating redundant (weak or little-used) synaptic connections to eliminate extraneous neurocircuit noise and increase the efficiency of neuronal transmission. The synaptic bloom-and-prune process is an important component of the fundamental neurophysiological process by which learning occurs through apperception; this learning dependent on the environment in which the learning occurs through the cellular mechanisms of long-term potentiation (LTP) and long-term

  Long-Term Potentiation and

Long-Term Depression

• Long-term potentiation (LTP) is defined as the

  development of a long-lasting synaptic strength

  or vitality between a pair of presynaptic and postsynaptic neurons as a product of the interactivity of the pair. The opposite of LTP is long-term depression (LTD), which produces a long-lasting decrease in synaptic strength between a pair of neurons. LTP and LTD are processes by which chemical synapses are able to change their strength, constituting a principal cellular mechanism of learning, as memories and

  experience are encoded by the modification of

  the strength of synaptic connections that form
• LTP is understood as the mechanism of the principle des i ed Ca la “hatz as ells that fi e togethe i e togethe “hatz , ased o He ia theory developed in 1949 by Canadian psychologist Donald Hebb (Hebb 1949) that rather than forming new neurons (neurogenesis), memories are formed (that is, experiences are encoded) by strengthening the connections (the synaptic interfaces) between existing neurons to improve the effectiveness of their communication. By the processes of both metabolic changes and the growing of new connections (i.e., new synaptic interfaces), neurons enhance their _{Shatz CJ (1992). The developing brain. Scientific American 267(3): 60-67. Hebb DO (1949). The organization of behavior. New York, NY: Wiley & Sons.}

  ability to communicate.

• In basic Hebbian theory, the persistence or repetition of a reverberatory activity tends to induce lasting cellular changes that add to its stability, for example, when an axon of cell A is contributory in exciting the axon of cell B and repeatedly or persistently takes part in firing it, growth processes and metabolic changes are generated in one or both cells such that A s effi ie i fi i g B that is, the st e gth of the synaptic connection between A and B) is increased, leading to a longer potentiation of cell A when firing cell B.
• LTP and LTD are persistent processes, LTP lasting from several minutes to many months, and it is this persistence that leads to the cellular changes that affect neuronal patterns of interconnectivity.

• Though there are several types of long-term potentiation, they can basically be divided into Hebbian and non-Hebbian types. Hebbian LTP requires simultaneous pre- and postsynaptic depolarization for its induction, as opposed to Non-Hebbian LTP which is induced without simultaneity of depolarization.
• A special type of Non-Hebbian LTP, known as anti-Hebbian LTP, requires simultaneous presynaptic depolarization and relative postsynaptic hyperpolarization for its induction.

• Low-level activation of an excitatory pathway can produce what is known as long-term depression (LTD) of synaptic transmission in many areas of the brain. Hebbian LTD is induced by a minimum level of postsynaptic depolarization and

  simultaneous increase in the intracellular calcium

  concentration at the postsynaptic neuron. Alternatively, LTD can be initiated at inactive

  synapses if the calcium concentration is raised to

  the minimum required level by heterosynaptic activation, or if the extracellular concentration is raised. These alternative conditions capable of causing LTD differ from the Hebbian rule, and instead depend on modulated as opposed to potentiated activity.

• There are two basic types of long-term depression, homosynaptic LTD, which is directly input-specific, and heterosynaptic LTD, which results from a modulated rather than potentiated effect.
• In homosynaptic LTD the activity in an individual neuron alters the efficiency of the synaptic connection between that neuron (the presynaptic neuron) and its target (the postsynaptic neuron) where the synaptic connection is typically weakened as a result of low-frequency potentiation or an extended period of no potentiation in the presynaptic neuron.

• In heterosynaptic LTD the activity of a particular neuron (a modulatory neuron or interneuron) results in changes in the strength of the synaptic connection between another pair of neurons through the release of neuromodulators that effect the efficacy of the synapse of the other pair of neurons. The weakening of the synaptic connection between the other pair of neurons is independent of the activity of the presynaptic or postsynaptic neuron of the pair. This type of LTD is referred to as a process of modulatory
• Neuromodulators (in particular, serotonin and dopamine) differ from classical neurotransmitters. Typically, neuromodulators do not directly generate electrical responses in target neurons. Rather, the release of neuromodulators often alters the efficacy of neurotransmission in nearby chemical synapses. Furthermore, the impact of neuromodulators is often quite long lasting in comparison to classical neurotransmitters.

• LTD is an important process that features in selectively weakening specific synapses in order to make constructive use of the selective strengthening process of LTP. This is necessary for two vital reasons.
• In the first, if synapses were allowed to continue increasing in strength and all synapses reached maximum strength with no mechanism for reducing synaptic strength, no new information could be encoded, since synaptic strength modulation is an indispensable element in the process by which new experience and new learning are registered in the brain.

• In the second, if all synapses were permanent, regardless of lack of efficiency or use, not only would the number of

  synapses reach a ceiling level very early in a

  pe so s life, p e e ti g the ge e atio of any new neuronal connections, but also neurocircuit efficiency would be highly compromised by a diffusion of synaptic noise created by the extraneous or irrelevant synapses that, through inactivity resulting from the changing circumstances of life, lost their usefulness in a specific neuronal connection.
• What this means is that, for a person to continue to perceive and assimilate new experiences throughout the pe so s life he the actual number of synapses are kept at a relatively stable count (with perhaps some natural reduction) throughout adult life (at a maximum estimate of 500 trillion), superfluous synapses are eliminated both to minimize neurocircuit noise and to make room for new synaptic connections in recognition of, and reaction to, ongoing new environmental stimuli and the continuing experiences of life and learning, as the generation of new synapses (both in increasing the connective strength between a pair of presynaptic and postsynaptic neurons, and in the construction of new interconnections of neuronal circuits) is an essential component of the process by which new experience and new learning are registered in the brain.

• One of the essential components of the critical synaptic elimination process is synaptic pruning by microglial cells in conjunction with the mechanism of long-term depression that weakens the less used, redundant and ineffectual synapses and marks the ineffective synapses for elimination through the macrophagic action of microglia in response to the constant monitoring of the condition of synaptic connections. Synapses that have been weakened by the process of LTD are sensed by the monitoring microglial cells and
• Regulatory synaptic pruning in the brain constituting the life-long learning process has also often been referred to as small-scale axon terminal arbor pruning, reflecting the position that synaptic pruning is basically a mechanism of disengagement of axon terminals from synaptic connections, which may include the processes of axon degeneration, axon shedding or axon retraction; however the particular molecular process remains unclear with a number of new studies implicating, as previously described, phagocytosis by

  microglial cells as an integral process of both developmental and

  ongoing homeostatic synaptic pruning in the brain (Tremblay et al.

  2011; Paolicelli et al. 2011: Yong 2014; Wake et al. 2013; Hughes

  _{Hughes V (2012). Microglia: The constant gardeners. Nature 485(7400): 570-2. Ji K, Miyauchi J & Tsrika SE (2013). Microglia: An active player in the regulation of synaptic activity. Neural Plasticity} 2012; Ji et al. 2013). _{2013. Article ID 627325. structure and function. Trends in Neuroscience 36(4): 209-17.} Journal of Neuroscience 31(45): 16064-69.

  Yong E (2014). Pruning synapses improves brain connections. The Scientist. www.the-

• Synaptic pruning in brain development has been defined as consisting of two main phenomena, synapse disassembly and process elimination.
• – Synapse disassembly has been defined as an extremely dynamic process of the removal of only a small subpopulation of synaptic connections that is to large degree common throughout the developing nervous system.

  In synapse disassembly synapses relatively stronger than neighboring competing synapses that input to an identical target seem to diminish in size and shift position to usurp that of the competitive input, the stronger synapse maintaining its innervation of the target with the weaker input both disassembling its

• – Process elimination is a phenomenon that occurs in the regressive stages of development and consists of both the small-scale pruning of dendrites in the neocortex, and the large-scale pruning of long axon collaterals of layer V cortical projections that can reach millimeters in length.

  It has been suggested that developmental process elimination can involve a number of different cellular mechanisms ranging from retraction to degeneration with considerable variability across the different regions of the nervous system.

• In addition to all the various mechanisms of synaptic pruning discussed above, it has also been determined that astrocytes play an indispensable role, not only in synaptic pruning in the brain but also in synaptogenesis and LTP (see

  for example Ota, Zanetta & Hallock 2015; Chung

  et al. 2013, Tasdemir-Yalmaz & Freeman 2015,

  Clarke & Barres 2013), and are therefore critical

  to synaptic strength modulation in the brain.

  _{Chung WS, Clarke LE, Wang GX, Stafford BK, Sher A, Chakraborty C, Joung J, Foo LC, Thompson A, Chen C, Smith}

  _{SJ & Barres BA (2013). Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways. Nature 504(7480): 394-400. doi: 10.1038/nature12776.}

  Clarke LE & Barres BA (2013). Emerging roles of astrocytes in neural circuit development. Nature Reviews _{Neuroscience 14(5): 311-21. doi: Ota Y, Zanetta AT & Hallock RM (2013). The role of astrocytes in the regulation of synaptic plasticity and memory formation. Neural Plasticity 2013. Article ID 185463.} . _{Tasdemir-Yalmaz OE & Freeman MR (2015). Astrocytes engage unique molecular programs to engulf pruned}

_{neuronal debris from distinct subsets of neurons. Genes and Development 28(1): 20-33.}

_{doi:10.1101/gad.229518.113.}

• In all the previous discussion of synaptic strength modulation in the brain and latterly synaptic pruning in regulating relative neuronal connective strength, we have considered the chemical synapse exclusively; however, recent studies have identified that a different type of synapse in the brain, the electrical synapse, plays a pivotal role in modulating neuronal activation readiness and firing strength.

  Structure and function of gap junctions at electrical synapses. Gap _{junctions consist of hexameric complexes formed by the coming together of subunits called connexons, which are present in both the to one another, creating electrical continuity between the two cells.} pre- and postsynaptic membranes. The pores of the channels connect

  _{permit current to flow passively through intercellular channels. This current flow} At electrical synapses, gap junctions between pre- and postsynaptic membranes

• Studies have shown that not only do chemical synapses

  modulate electrical synapses (see for example Smith &

  Pereda 2003) but that electrical synapses are critical for

  chemical synapse function (see for example Lieff 2014)

  and are subject to both long-term potentiation (LTP) and

  long-term depression (LTD) like chemical synapses (see

  for example Haas, Zavala & Landisman 2011; and Wang,

  Neely & Landisman 2015) that effect the excitability of

  the postsynaptic neuron. _{Haas JS, Zavala B & Landisman CE (2011). Activity-dependent long-term depression of electrical synapses. Science 334(6054): 389} –93. doi: 10.1126/science.1207502. _{Lieff J (2014). Electrical synapses are critical for chemical synapse function. jonlieffmd.com/blog/electrical-synapses-are-critical-for-chemical-synapse-} function#comment-1565109975. _{Smith M & Pereda AE (2003). Chemical synaptic activity modulates nearby electrical synapses. Proceedings of the National Academy of Sciences of the United States of America} 100(8): 4849-54. doi: 10.1073/pnas.0734299100. _{Wang Z, Neely R & Landisman CE (2015). Activation of group I and group II metabotropic glutamate receptors causes LTD and LTP of electrical synapses in the rat thalamic}

  reticular nucleus. Journal of Neuroscience 35(19): 7616-25. doi: _{10.1523/JNEUROSCI.3688-14.2015.}

• • It has been estimated that a single neuron in the human brain can have

  up to 20,000 synapses (one type of neuron, the Purkinje cell in the cerebellum, may have as many as 170-200 thousand synapses as determined in rat studies

• – see for example Napper and Harvey 1988) and that there are typically somewhere on the order of 86 billion neurons in the adult human brain, with the maximum number of synapses in the adult human brain estimated at between 150-500 trillion. With the interminable complexity of incalculable combinations

  and permutations of all the interactions of synaptogenesis, synaptic

  blooming and pruning, LTP/LTD, synaptic scaling, chemical and electrical synapse reciprocal interplay, and the multitudinous synaptic input and output of a single neuron in interconnection with a vast array of other neurons, it is clear that patterns of neuronal interconnections in the human brain are practically infinite, constantly

  changing, and that each macrostructural change is the mechanism of

  neurophysiological representation of the perception and internalization of an element of a new experience, thought, or memory, all the elements associated with each experience interlinked by specific patterns of neuronal interconnectivity constituting the process of apperception expressed through the ceaseless _{Oct. 2004: doi: 10.1002/cne.902740204.}

  _{in the cerebellum of the rat. Journal of Comparative Neurology 274(2): 168-77. Published online 9}

  _{Napper RMA & Harvey RJ (1988). Number of parallel fiber synapses on an individual Purkinje cell}

  neuroplasticity of the human brain.

• • However vast the above estimated numbers of synaptic connections in the

  ai , the a pale i ag itude to the t ue o ple it of the ai s interconnections. A new study has discovered synaptic connectivity never before seen. Introducing innovative 3D color-coded brain imaging at

nanoscale resolution using a new automated tape-based serial electron

microscopy technique, the study provided a detailed analysis of the o e ti it et ee e itato a o s a d spi es i a ouse s ai which suggests that axons are more likely to innervate multiple spines of the

same dendrite than expected by chance encounters based on overlap,

revealing that the complexity of the brain is much more than what had

ever been imagined (Kasthuri et al. 2015). In the study the researchers

found that the sheer magnitude of neuronal connections that make up the brain imposed a huge challenge

• – one that made the authors question whether the finished product justified its use, concluding that their effort la s a e the ag itude of the p o le o f o ti g neuroscientists who seek to u de sta d the ai . Noti g that the deg ee of al ost i o p ehe si le o ple it the dis o e ed as o se ed i a ouse s brain and considering that a human brain has far more neuronal complexity, the resistance of the human brain to revealing its deep secrets is clearly demonstrated in its almost-impossible-to-understand, and, _{Kasthuri N, Hayworth KJ, Berger DR, Schalek RL, Conchello JA, Knowles-Barley S, Lee D, Vázquez-} perhaps, truly-impossible-to-understand intricacies. _{Vogelstein JT, Burns R, Sussman DL, Priebe CE, Pfister H & Lichtman JW (2015).}

  _{Reina A, Kaynig V, Jones TR, Roberts M, Morgan JL, Tapia JC, Seung HS, Roncal WG,}