Lecture 5 Brain Development and Plasticity

Maturation of the Vertebrate Brain The human central nervous system begins to form when the embryo is approximately two weeks old The dorsal surface thickens forming a neural tube surrounding a fluid filled cavity The forward end enlarges and differentiates into the hindbrain, midbrain, and forebrain The rest of the neural tube becomes the spinal cord

Maturation of the Vertebrate Brain (cont’d.) The fluid-filled cavity becomes the central canal of the spinal cord and the four ventricles of the brain The fluid is the cerebrospinal fluid

Maturation of the Vertebrate Brain (cont’d.) At birth, the human brain weighs approximately 350 grams By the first year, the brain weighs approximately 1000 grams The adult brain weighs 1200-1400 grams

Maturation of the Vertebrate Brain (cont’d.) The development of neurons in the brain involves the following processes: Proliferation Migration Differentiation Myelination Synaptogenesis

Maturation of the Vertebrate Brain (cont’d.) Proliferation refers to the production of new cells/ neurons in the brain primarily occurring early in life Early in development, the cells lining the ventricles divide Some cells become stem cells that continue to divide Others remain where they are or become neurons or glia that migrate to other locations

Maturation of the Vertebrate Brain (cont’d.) Migration refers to the movement of the newly formed neurons and glia to their eventual locations Some don’t reach their destinations until adulthood Occurs in a variety of directions throughout the brain Occurs via cells following chemical paths in the brain of immunoglobins and chemokines

Maturation of the Vertebrate Brain (cont’d.) Differentiation refers to the forming of the axon and dendrite that gives the neuron its distinctive shape The axon grows first either during migration or once it has reached its target and is followed by the development of the dendrites

Maturation of the Vertebrate Brain (cont’d.) Myelination refers to process by which glia produce the fatty sheath that covers the axons of some neurons Myelin speeds up the transmission of neural impulses First occurs in the spinal cord and then in the hindbrain, midbrain and forebrain Occurs gradually for decades

Maturation of the Vertebrate Brain (cont’d.) Synaptogenesis is the final stage of neural development and refers to the formation of the synapses between neurons Occurs throughout the life as neurons are constantly forming new connections and discarding old ones Slows significantly later in the lifetime

Maturation of the Vertebrate Brain (cont’d.) Originally believed that no new neurons were formed after early development Later research suggests otherwise: Stem cells are undifferentiated cells found in the interior of the brain that generate “daughter cells” that can transform into glia or neurons New olfactory receptors also continually replace dying ones

Maturation of the Vertebrate Brain (cont’d.) Development of new neurons also occurs in other brain regions Example: songbirds have a steady replacement of new neurons in the singing area of the brain Stem cells differentiate into new neurons in the adult hippocampus of mammals and facilitate learning

Maturation of the Vertebrate Brain (cont’d.) Different cells have different average life spans Skin cells are the newest; most are under a year old Heart cells, on the other hand, tend to be as old as the person Mammalian cerebral cortexes form few or no new neurons after birth

Pathfinding by Axons Axons must travel great distances across the brain to form the correct connections Sperry’s (1954) research with newts indicated that axons follow a chemical trial to reach their appropriate target Growing axons reach their target area by following a gradient of chemicals in which they are attracted by some chemicals and repelled by others

Pathfinding by Axons (cont’d.) When axons initially reach their targets, they form synapses with several cells Postsynaptic cells strengthen connection with some cells and eliminate connections with others The formation or elimination of these connections depends upon input from incoming of axons

Pathfinding by Axons (cont’d.) Some theorists refer to the idea of the selection process of neural connections as neural Darwinism In this competition amongst synaptic connections, we initially form more connections than we need The most successful axon connections and combinations survive while the others fail to sustain active synapses

Determinants of Neuronal Survival Levi-Montalcini discovered that muscles do not determine how many axons form; they determine how many survive Nerve growth factor (NGF) is a type of protein released by muscles that promotes the survival and growth of axons The brain’s system of overproducing neurons and then applying apoptosis enables the exact matching of the number of incoming axons to the number of receiving cells

Determinants of Neuronal Survival (cont’d.) A neurotropin is a chemical that promotes the survival and activity of neurons (i.e., NGF) Axons that are not exposed to neurotropins after making connections undergo apoptosis Preprogrammed mechanism of cell death Therefore, the healthy adult nervous system contains no neurons that failed to make appropriate connections

Determinants of Neuronal Survival (cont’d.) The elimination of massive cell death is part of normal development and maturation After maturity, the apoptotic mechanisms become dormant The visual cortex is actually thicker in blind people because due to a lack of visual stimuli It cannot prune out ineffective neurons

The Vulnerable Developing Brain Early stages of brain development are critical for normal development later in life A mutation on one gene can lead to many defects Chemical distortions in the brain during early development can cause significant impairment and developmental problems

The Vulnerable Developing Brain (cont’d.) Fetal alcohol syndrome is a condition that children are born with if the mother drinks heavily during pregnancy The condition is marked by the following: Hyperactivity and impulsiveness Difficulty maintaining attention Varying degrees of mental retardation Motor problems and heart defects Facial abnormalities

The Vulnerable Developing Brain (cont’d.) The dendrites of children born with fetal alcohol syndrome are short with few branches Exposure to alcohol in the fetus brain suppresses glutamate and enhances the release of GABA Many neurons consequently receive less excitation and exposure to neurotrophins than usual and undergo apoptosis

The Vulnerable Developing Brain (cont’d.) Children of mothers who smoked cigarettes or used cocaine during pregnancy are at increased risk for ADHD and other behavioral deficits Children of mothers who used antidepressant drugs during pregnancy have an increased risk of heart problems Mother’s stress can affect the health of her children

Differentiation of the Cortex Neurons in different parts of the brain differ from one another in their shape and chemical components Immature neurons transplanted to a developing part of the cortex develop the properties of the new location Neurons transplanted at a later stage of development develop some new properties but retain some of old properties Example: ferret experiment

Fine-Tuning by Experience The brain has some limited ability to reorganize itself in response to experience Axons and dendrites continue to modify their structure and connections throughout the lifetime Dendrites continually grow new spines The gain and loss of spines indicates new connections, which relates to learning

Fine-Tuning by Experience (cont’d.) Rats raised in an enriched environment develop a thicker cortex and increased dendritic branching Measurable expansion of neurons has also been shown in humans as a function of physical activity The thickness of the cerebral cortex declines in old age, but much less in those that are physically active

Fine-Tuning by Experience (cont’d.) Once believed that teaching a child a difficult concept (e.g., Greek, advanced math, etc.) would enhance intelligence in other areas This concept is known as “far transfer” Evidence shows that skills associated with the practiced task transfer, but not other skills The brain cannot be “exercised” like a muscle

Fine-Tuning by Experience (cont’d.) Neurons also become more finely tuned and responsive to experiences that have been important in the past This may account for the fact that blind people often have enhanced tactile senses and increased verbal skills The occipital lobe normally dedicated to processing visual information adapts to also process tactile and verbal information

Fine-Tuning by Experience (cont’d.) Extensive practice of a skill changes the brain in a way that improves the ability for that skill People who learned to read as adults compared to those who never learned how to read show more gray matter and greater thickness in part of the corpus callosum

Fine-Tuning by Experience (cont’d.) MRI studies reveal following: The temporal lobe of professional musicians in the right hemisphere is 30% larger than non-musicians Thicker gray matter in the part of the brain responsible for hand control and vision of professional keyboard players Some professions may require skills that are known to form in brain areas before birth (e.g., phoneticians)

Fine-Tuning by Experience (cont’d.) Practicing a skill reorganizes the brain to maximize performance of that skill Certain types of training may also exert a bigger effect if they begins early in life Example: musicians who began before age 7 showed advantages over those who started later in life

Fine-Tuning by Experience (cont’d.) Focal hand dystonia or “musicians cramp” refers to a condition where the reorganization of the brain goes too far The fingers of musicians who practice extensively become clumsy, fatigue easily, and make involuntary movements This condition is a result of extensive reorganization of the sensory thalamus and cortex so that touch responses to one finger overlap those of another

Brain Development and Behavioral Development Adolescents tend to be more impulsive than adults Impulsivity can be a problem when it leads to drinking, risky driving, sex, etc. Antisaccade task: looking away from a powerful attention-getter Gradually improves during the teenage years Adolescents tend to “discount the future”

Brain Development and Behavioral Development (cont’d.) Adolescents are not equally impulsive in all situations Peers, amount of time to make decisions, etc., effect their decisions Adolescents’ prefrontal cortexes are relatively inactive in certain situations, but this may or may not be the cause of impulsivity

Brain Development and Behavioral Development (cont’d.) Neurons alter synapses more slowly in old age Brain structures begin to lose volume Research underestimates older people: People vary in respect to intellectual decline Older people have a greater base of knowledge and experience, and many find ways to compensate for losses

Plasticity After Brain Damage Survivors of brain damage show subtle to significant behavioral recovery Some of the mechanisms of recovery include those similar to the mechanisms of brain development such as the new branching of axons and dendrites

Brain Damage and Short-Term Recovery Possible causes of brain damage include: Tumors Infections Exposure to toxic substances Degenerative diseases Closed head injuries

Brain Damage and Short-Term Recovery (cont’d.) A closed head injury refers to a sharp blow to the head that does not puncture the brain One of the main causes of brain injury in young adults After a severe injury, recovery can be slow and incomplete A stroke or cerebrovascular accident is temporary loss of blood flow to the brain Common cause of brain damage in elderly

Brain Damage and Short-Term Recovery (cont’d.) Types of strokes include: Ischemia: the most common type of stroke, resulting from a blood clot or obstruction of an artery Neurons lose their oxygen and glucose supply Hemorrhage: a less frequent type of stroke resulting from a ruptured artery Neurons are flooded with excess blood, calcium, oxygen, and other chemicals

Brain Damage and Short-Term Recovery (cont’d.) Ischemia and hemorrhage also cause: Edema: the accumulation of fluid in the brain resulting in increased pressure on the brain and increasing the probability of further strokes Disruption of the sodium-potassium pump leading to the accumulation of potassium ions inside neurons

Brain Damage and Short-Term Recovery (cont’d.) Edema and excess potassium triggers the release of the excitatory neurotransmitter glutamate The overstimulation of neurons leads to sodium and other ions entering the neuron in excessive amounts Excess positive ions in the neuron block metabolism in the mitochondria and kill the neuron

Brain Damage and Short-Term Recovery (cont’d.) A drug called tissue plasminogen activator (tPA) breaks up blood clots and can reduce the effects of an ischemic strokes Research has begun to attempt to save neurons from death by: Blocking glutamate synapses Blocking calcium entry

Brain Damage and Short-Term Recovery (cont’d.) One of the most effective laboratory methods used to minimize damage caused by strokes is to cool the brain Mechanisms are uncertain but cooling someone during the first three days is beneficial

Brain Damage and Short-Term Recovery (cont’d.) Cannabanoids have also been shown to potentially minimize cell loss after a brain stroke Benefits are most likely due to cannabinoids anti-inflammatory effects Research shows that they are most effective in laboratory animals when taken before the stroke

Later Mechanisms of Recovery Following brain damage, surviving brain areas increase or reorganize their activity Diaschisis: decreased activity of surviving neurons after damage to other neurons Because activity in one area stimulates other areas, damage to the brain disrupts patterns of normal stimulation Use of drugs (stimulants) to stimulate activity in healthy regions of the brain after a stroke may be a mechanism of later recovery

Later Mechanisms of Recovery (cont’d.) Destroyed cell bodies cannot be replaced, but damaged axons do grow back under certain circumstances If an axon in the peripheral nervous system is crushed, it follows its myelin sheath back to the target and grows back toward the periphery at a rate of about 1 mm per day

Later Mechanisms of Recovery (cont’d.) Damaged axons only regenerate one to two millimeters in mature mammals Paralysis caused by spinal cord damage is relatively permanent Scar tissue makes a mechanical barrier to axon growth Glia cells reacting to damage in CNS release chemicals that inhibit axon growth Research on building protein bridges may help

Later Mechanisms of Recovery (cont’d.) Collateral sprouts are new branches formed by other non-damaged axons that attach to vacant receptors Cells that have lost their source of innervation release neurotrophins that induce axons to form collateral sprouts Over several months, the sprouts fill in most vacated synapses and can be useful, neutral, or harmful

Later Mechanisms of Recovery (cont’d.) Postsynaptic cells deprived of synaptic inputs develop increased sensitivity to the neurotransmitter to compensate for decreased input Denervation supersensitivity: the heightened sensitivity to a neurotransmitter after the destruction of an incoming axon Can cause consequences such as chronic pain

Later Mechanisms of Recovery (cont’d.) Phantom limb refers to the continuation of sensation of an amputated body part The cortex reorganizes itself after the amputation of a body part by becoming responsive to other parts of the body Original axons degenerate leaving vacant synapses into which others axons sprout

Later Mechanisms of Recovery (cont’d.) Phantom limb can lead to the feeling of sensations in the amputated part of the body when other parts of the body are stimulated e.g., a touch on the face can bring about the experience of a phantom arm Use of an artificial limb can reduce the likelihood of experiencing phantom limb

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Later Mechanisms of Recovery (cont’d.) Deafferentated limbs are limbs that have lost their afferent sensory input Can still be used but are often not because use of other mechanisms to carry out the behavior are easier The study of the ability to use deafferentated limbs has led to the development of therapy techniques to improve functioning of brain damaged people Focus on what they are capable of doing