NEUR 1203 Lecture 4-7 PDF - Human Neurodevelopment, Neural Tube
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These lecture notes titled NEUR 1203 Lecture 4-7 cover topics of neurodevelopment and neurogenesis. The document discusses stages of human and neural tube formation, neuron and glial cell formation, and factors influencing stem cell production and brain growth. Key topics include neural development, cell migration and differentiation.
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2/9/25, 5:09 PM NEUR 1203 LECTURE 4 - 7 NEUR 1203 LECTURE 4 - 7 Day 1: fertilization, zygote is a single cell...
2/9/25, 5:09 PM NEUR 1203 LECTURE 4 - 7 NEUR 1203 LECTURE 4 - 7 Day 1: fertilization, zygote is a single cell composed of half the mothers DNA and half of the fathers Day 2: Cells begin to divide, which continues to occur for our entire life Day 15: embryonic disc, cells form several layers, would still need a microscope to see Day 18-21: formation of neural plate and groove, composed of neural tissue - this is known as neuralation Day 22 - 24: neural tube forms from the neural Stages of human neurodevelopment plate, after 3 weeks there are rapid changes, creates a whole in brain which creates the ventricles, neural tube goes on to form the spine Day 49 (7 weeks): embryo begins to resemble human, at 6 weeks we can see on an ultrasound Day 100 (14 weeks) : brain begins to resemble human 7 Months: formation of gyri and sulci, not as complex, only small grooves and bumps 9 Months: full human brain, cellular structure is still very different, becomes more complex aka neuralation embryo consists of 3 layers 1. endoderm 2. ectoderm Formation of the neural tube 3. mesoderm around day 18 the ectoderm thikens and folds up into itself due to cells growing and pushing around day 21 a hollow cylinder shape is formed which is the neural tube https://knowt.com/flashcards/e95425ab-0819-467f-9ec1-477cb95acc07?isNew=true 1/15 2/9/25, 5:09 PM NEUR 1203 LECTURE 4 - 7 stem cells: makes one of itself and one progenitor cell, does not self renew progenitor cells: percursor cells that can also divide into nondividing cells (ie. either How are neurons and glia formed? neuroblast or glioblast) neuroblast: cell that will eventually form into a neuron either a interneuron or pyramidal neuron glioblast: cell that will eventually form into glial cell, either an oligodendroglia or astrocyte 1. prolactin: hormone that increases to very high levels during pregnancy = increase in fetal neural stem cell production 2. Gene transcription: genes get turned “on” through transcription, which influence the fate of the stem cell neuron instead of skin cell chemicals that influence stem cell production 3. Epigenetics: helps to control which genes are turned off and on, different cells require different genes and proteins, occurs a lot during development, typically occurs in response to signals from the cells environment (ie. hormones stress) DNA methylation: addition of a methyl group that turns the gene off how it goes from stem cell to progenitor to glial neuron help nourish (trophic) cells by supporting growth and differentiation, usually produced by epithellal cells not neurons neurotrophic factors 1. epidermal growth factor: stimulates neural stem cells to turn into progenitor cells 2. Basic fibroblast growth factor: stimulates progenitors into neuroblasts (young neurons), does NOT effect stem cell production stages of neural/glial growth 1. Cell birth: neurogenesis,gliogenesis,largely https://knowt.com/flashcards/e95425ab-0819-467f-9ec1-477cb95acc07?isNew=true 2/15 complete by 5 months (prenatally), 2/9/25, 5:09 PM NEUR 1203 LECTURE 4 - 7 during this time brain is resillient to injuries (ie. teratogens and/or trauma) embryo will have all the neurons it needs 2. Cell Migration: traveling to final destination, after neurogenesis is complete lasts for 6 weels, moves away from ventricular zone 3. Cell differentiation: cells develop the spcific tools/skills, begins during migration and continues after migration is complete, complete at time of birth (ie. becomes a dopamine neuron, GABA neuron..etc.) 4. Cell Maturation: dendritic development, axonal growth, occurs for years, well into adulthood, growth of dendrites and axons, this is what allows for chemical transmission to occur 5. Synaptogenesis: formation of synapses, each neuron begins forming its own networks, synapses with hundreds of thousands of other neurons 6. Cell Death: apoptosis, if you dont use it you lose it 7. Myelogenesis: formation of myelin sheath, neuronal networks become more efficient in their communication, sign og neurodevelopmental maturity, occurs well in adulthood. helps axons communicate more efficiently, mature = complete genesis Cell migration begins around 6 weeks cortex is highly organized into layers of cells ( layer I to layer VI) builds from the inside out, layer VI is on the inside and builds from there Subventricular zone: contains a primitive map, cells from a specific region in the SVZ are prediposed to migrate to specific areas of the cortex https://knowt.com/flashcards/e95425ab-0819-467f-9ec1-477cb95acc07?isNew=true 3/15 cells follow set paths due to radial glia - glial 2/9/25, 5:09 PM NEUR 1203 LECTURE 4 - 7 cells that create a oath from the SVZ to the top of the cortex progenitor cells follow the path cortical formation is extremely ordered intracellular (between cells) signals restrict the type of cells that are formed, the emergence of a cell type in a specific area depend on 3 things that all work together 1. genetic expression - ex: progenitor — Cell Differentiation > neuroblast —> inhibitory/excitatory —> pyrimidal cell 2. timing, genes arent always active, they can turn off and on 3. signals found in the local environment (ie. neurotrophic factors) immediately after diferentiation, cells are still small in structures young neurons need to grow 2 main oarts to function 1. dendrites - provide surface area for synapse formation arborization - branching of dendrites (like a tree in the spring growing back) spine formation - components to make contact with axon terminals, where synapses occurs Cell maturation 2. Axons - extend to the target area to make contact with other neurons, can influence the cell type of the post- synaptic cell, axons are guided towards targets by various chemicals that can attract or repel them growth cones - extension of developing axon filopod - shoots that come off of the growth cones, if they reach target (ie.dendrite) then the rest of the growth cones will follow and establish a complete axon Growth cone movement of the growth cones depends on https://knowt.com/flashcards/e95425ab-0819-467f-9ec1-477cb95acc07?isNew=true 4/15 1. Cell adhesion molecules: found on 2/9/25, 5:09 PM NEUR 1203 LECTURE 4 - 7 the surface of cells, allows the growth cone to go to a specific cell, or in the intracellular space, provides something the growth cones can attach to 2. Tropic molecules: secreted from target cells and direct to turn away or to attract, guide neurons outside of cells netrin: brings cone towards a cell semaphorins: repels growth cones and forces axon to move out after growth cone attaches it forms a synapse estimated that the human brain contains 10 ^ 14 synapses amount of organization of synapses thought to be guided by local environmental cues & signals Synaptic development 5 months: simple synaptic contacts 7 months: deep cortical layers have developed intense synaptic organization (ie. layer IV, layer V..) after birth: amount of synapses increases drastically, number doubles between 2-4 months after birth, after 1 yr you get a oeak and have most of the synapses Synaptic pruning start off with a lot more synapses then you need and gets less over time, do not need excess ones formed at birth influenced by many factors like genetic signals, life experiences, hormones, stress, etc. 40 % loss of synapses from childhood to adulthood, if it is not intergrated into a circuit Neural Darwinism: competition for finite resources leads to only those that are best suited for the environment to survive neurons are dependent on forming synapses, these connection allow them to absorb neurotrophic factors https://knowt.com/flashcards/e95425ab-0819-467f-9ec1-477cb95acc07?isNew=true 5/15 Nerve growth factor: neurotrophic factor is 2/9/25, 5:09 PM NEUR 1203 LECTURE 4 - 7 produced by cells that help you regulate neuron survival, made by cortical cells and absorbed by cholinergic cells in the basal forebrain only so much NGF is produced neurons dont receive enough will express genes that lead to apoptosis mostly complete by age 20, there are exceptions 1. language areas actually increase in grey matter density as you age - neurons do not die off they become more complex (ie. learning a new language) 2. language is a fundamental part of human cognition and learning 3. thought to occur due to the unique timeline of language acquisition and its role in learning throughout life last process to occur during development myelin in CNS is formed by oligodendrocytes - continue to develop throughout life myelination occurs at different rates in different areas of the cortex, whatever is more Myelination important is myelinated first myelination can be a marker for neuronal maturity regions that are myelinated early, control simple movements (ie. visual cortex) regions that are myelinated later, control higher mental functions (ie. frontal cortex) procress where the brain in modeled by experience (ie. culture, language, relationships, values, behaviour..etc.) Neuroplasticity a persons culture, which is an important aspect of someones environment is an experience that can mold the brain-different cultures would have structural differences leading to the differences in behaviour https://knowt.com/flashcards/e95425ab-0819-467f-9ec1-477cb95acc07?isNew=true 6/15 2/9/25, 5:09 PM NEUR 1203 LECTURE 4 - 7 tested how early life experiences affect brain development and learning. He compared two groups of rats: 1. Lab Rats – Raised in standard cages with minimal stimulation. 2. Home-Raised Rats – Allowed to explore and interact with a normal Donald Hebb experiment with rats home environment. When tested in a maze, the home-raised rats performed better, solving it faster and making fewer mistakes. This showed that early enriched environments improve brain function and learning abilities, supporting the idea that experience shapes brain development. tactile stimulation - speeds up growth of premature infants (ie.skin to skin, breastfeeding,petting..etc.) environmetal influence on the brain lab setting - brushing rats for 15 mins 3x a day for the first 3 weeks, speeds up development leads to neurons that are larger and richer in synapses in cortex of adults, more dendrites, more axons, overall more dense dogs put in the dark with no stimulation caused no reactions to people or other dogs, loss of all pain sensation, unable to do a maze task and overall poor brain developmentr due to lack of stimulation monkeys removed from parents after birth abnormal experiments in brain development were unable to form relationships, abnormal intellectual and social behaviours orphans who were not in school or with families, were malnourished and had severe motor and cognitive defecits, luckily due to neuroplasticity the brain can develop more neurons in the future with proper stimulation Fragile X Syndrome most common inherited neurodevelopmental disorder aka martin-bell syndrime causes developmental delayes and intellectual disability - ranges from mild to severe https://knowt.com/flashcards/e95425ab-0819-467f-9ec1-477cb95acc07?isNew=true 7/15 due to mutations in the fragile X 2/9/25, 5:09 PM NEUR 1203 LECTURE 4 - 7 ribonucleoprotein 1 (FMR 1 gene) mutation causes X chromosome to look fragile/broken biological males and females are affected, males are more severe or susecptible because they only have one X chromone, for a female to have a severe case of fragile X it would have to affect both chromosomes (very rare) average age of diagnosis in males in 35-37 Epidemiology of Fragile X months average age of diagnosis in females is 42 months, usually detected later because it is less severe typically noticed by parents in the first 12- 16 months - typical milestones are not reached strong comorbitidy with ASD ranges from mild to severe - learning disorders to intellectual disability, females typically only have a mild defecit or normal intelligence low IQ that gets worse with age, possibly due Clinical features of Fragile X Syndrome to attentional issues - comorbidity with ADHD delays in certain intellectual milestones physical characteristics - long face, prominent jaw, macro-orchidism (abnormally large testicles), joint hypermobility, flat feet, not visible til puberty anxious in new situations - may lead to lashing out, overly common, due to abnormal circuitry difficulty making eye contact, leads to difficulty in social relationships Behavioural Features in Fragile X males typically have attentional issues and/or aggression and women especially tend to have social anxiety flapping/biting hands in social situations to relieve anxiety but can be physically damaging speech and language in Fragile X significant delays in word acquisition, one of the first signs of intellectual disability, wont speak til ages 3-5 https://knowt.com/flashcards/e95425ab-0819-467f-9ec1-477cb95acc07?isNew=true 8/15 impaired reading skills ie. grade 4 child can 2/9/25, 5:09 PM NEUR 1203 LECTURE 4 - 7 only read at the grade 1 level use of repetitive language, susually because they are trying to understand the words difficulty in communicating informative details (ie. how to get from one place to another, giving directions common to display sensory hypersensitivity, senses are heightened can be auditory, tactile or visual but auditory is the most common impaired sound habituatuon, reduced auditory sensory issues in Fragile X attention (ie. cannot tune out noise and cant listen for extended period of time) some show significant visuospatial impairments - cannot move round in soace correctly (ie. when driving cannot judge distances) Fragile X Messenger Ribonucleoprotein 1 - gene is silenced/loss of function, becomes a non-functional protein FMR protein is necessary for neurodevelopment as it regulates protein trabslation, especially in synapses caused by the addition of CGG repeats to the What causes FMR1 mutations promoter region of the FMR1 gene number of repeats correlates with severity < 45 = normal range 45-54 = intermediate/grey zone 55 - 200 = premutation, show specific issules later in life and is higher risk to give full mutation to offspring > 200 = full mutation https://knowt.com/flashcards/e95425ab-0819-467f-9ec1-477cb95acc07?isNew=true 9/15 2/9/25, 5:09 PM NEUR 1203 LECTURE 4 - 7 all of our cells contain DNA, which are instructions to make proteins that allow them to survive/carry out functions Chromosome Structure DNA gets stored in chromosomes inside of the nucleus - humans have 23 pairs pair 23 are the sex chromosomes female XX and male XY reproductive cells contain only one copy of a chromosome, only take on pair, move gives X and dad gives X or Y during fertilization, the chromosome from the mom and the dad join together to form a new chromomal pair in the offspring fragile X does NOT follow mandelian genetics —> mutations in FMR1 are passed down Basis of chromosomal inheritence depeding on which parent posses it mothers that are carriers of the premutation have increased risk of children with full mutation —> CGG repeats are unstable and tend to grow with maternal transmission, can pass mutation to either son or daughter Fathers only have one X chromosome and therefore only pass on the mutation to their daughters genes are highly structured and depend on the presence of a promoter for transcription to occur transcription: creation of mRNA, based on DNA Structure and transcription in Fragile X codons made from the nucleotides, promoter allows for the binding of RNA polymerase to the DNA chain and subsequent formation of mRNA too many CGG’s prevents the binding of RNA polymers FMR1 CGG mutation CGG repeates are found in the 5’ region of the DNA - part of the promoter and helps regulate binding of RNA polymerase inherently unstable = polymorphic causes DNA methylation (silencing of a gene) https://knowt.com/flashcards/e95425ab-0819-467f-9ec1-477cb95acc07?isNew=true 10/15 for a full mutation (> 200 repeats) gene is 2/9/25, 5:09 PM NEUR 1203 LECTURE 4 - 7 entirelly silenced and the protein is no longer produced premutation still is able to produce proteins and can get fragile X association, for females it is known as fragile X ovarian association regulates protein translation, acts as a break and slows down protein production protein translation is essential for synaptic Why is FMRP important? function, circuit formation,dendritic spine numbers, morphology and neurogenesis needs proteins to get through path, FMRP regulates this increasing protein translation is detrimental brain is similar to the immature brain before fine-tuned networks (ie. underdeveloped brains) smaller cerebral vermis, loss of this leads to motor dysfunction and mental retardation Neuroanatomical changes in Fragile X larger 4th ventricle, large ventricles push the syndrome brains and takes up space for further development increased caudate nucleus & HC increased spine density malformed spines - immature and look more like flopodia Neurophysiological changes in Fragile X Long term depression is increased which leads to impaired synaptic functioning constant low frequency stimulation of neurons leads to a weakened synapses through internalization of receptors characterized by smaller excitatory neurons in the post synaptic cell, less stimulation = less receptors = less ions LTD plays a role in protein synthesis, malformed spines occur since there is an increase in LTD, more LTD more protein synthesis = Bad FXS shows hyperexcitability in some brain regions, oversensitivity to stimuli - https://knowt.com/flashcards/e95425ab-0819-467f-9ec1-477cb95acc07?isNew=true 11/15 counterintuitive since LTD leads to reduced 2/9/25, 5:09 PM NEUR 1203 LECTURE 4 - 7 stimulation taken together overall their is a ESPS and ISPS imbalance that influence the symptpms Amygdala: lower inhibitory synapse number, GABA release, GABA vesicular content (less inhibition = more GO) Cortex: reduced inhibitory function by reduced Synaptic and neurotransmitter changes in FXS excitatory transmission onto GABA neurons ( less GO and less STOP) Striatum: increased GABA, more STOP Hippocampus: increased endocannabinoid activity that reduces GABA function (more STOP) required DNA testing from the child, sequenced for the specific region typically occurs between 35 to 37 months for makes and 42 months for female Diagnosis for FXS parents that carry the premutation may get their child tested during gestation amniocentesis: taking amniotic fluid chronic villus sampling: cell sample from the placenta no cure for FXS, cannot force protein to be made and reverse structural changes that occured during development but can treat comorbid features ADHD - adderal,ritalin Seizures - lithium carbonaye Current treatment for FXS Aggresssion/OCD - fluoxetine..etc. sleep issues - trazodone therapic can also help with remaining symptoms speech and language therapy occupational therapy interventions early on so kids can develop a long a normal timeline https://knowt.com/flashcards/e95425ab-0819-467f-9ec1-477cb95acc07?isNew=true 12/15 2/9/25, 5:09 PM NEUR 1203 LECTURE 4 - 7 genetic disorder causing delays in neural and physical development What is down syndrome? most common chromosomal condition occurs due to extra or partial copy of chromosome 21 highest risk factor is maternal age —> thought to occur due to higher ratio of eggs with extra chromosome epidemiology of down syndrome rate seems to be increasing up by 30% life expectancy of 47 yrs, many issues during development that increase risk of death early flattened face, especially bridge of the nose] almond eyes that slant uo short neck physical changes in Down syndrome small ears, overall short in height tongue tends to stick out small hands and feet poor muscle tone or loose joints ear infections or hearing loss vision problems or eye disease physiological problems in down syndrome dental problems more prone to infections or illnesses obstructive sleep apnea congenital heart disease usualy mild, moderate, rarely severe short attention span slow learning cognitive issues in down syndrome delayed language and speech development delayed motor skills mental health issues, early dimentia typically noticeable early in life and still able to develop proper communication skills behavioural changes in down syndrome impulsive behavioiur OCD https://knowt.com/flashcards/e95425ab-0819-467f-9ec1-477cb95acc07?isNew=true 13/15 poor judgement 2/9/25, 5:09 PM NEUR 1203 LECTURE 4 - 7 temper tantrums self talking unique talents strong social skills - highly empathetic during normal egg/sperm production, cells undergo meiosis during fertilization the 23 chromosomes from the mother and father come together to form 46 pairs all chromosomes are duplicated forming sister chromatids meiosis I separates the homologous chromosomes and forms 2 cells meiosis II separates the sister chromatids in cause of down syndrome both cells so when those divide and form 2 new cells in down syndrome there is an extra copy of chromosome 21, can be in a portion of cells this is known as mosaicism or all cells which is known as trisomy 21 there is an error in the steps of cell division and replication translocation: where an additional/partical copy of 21 binds to another chromosome usually 14, least common Trisomy 21: error in cell division causing an egg or sperm cell to have an extra Trisomy 21 and Mosaicism chromosome 21 - most common Mosaicism: normal egg/sperm and there is an error during early embryonic days leading to some cells having an extra chromosome 21 neuroanatomy of down syndrome smaller adult brain volume, volume decreased between ages 10-20 related to synpatic pruning, too many cells are getting pruned brachycephalic: small cerebellu, symplified gyri, smllaer head = smaller structures = less growth cortex: reduced number of neurons, decreased neruonal density, abnormal https://knowt.com/flashcards/e95425ab-0819-467f-9ec1-477cb95acc07?isNew=true 14/15 neuronal distribution in Layer II and IV, 2/9/25, 5:09 PM NEUR 1203 LECTURE 4 - 7 abnormal synaptic length and desnity less neurons being born at 17 weeks frontal lobe: reduced volume with fewer cells temporal lobe: reduced volume, reduced number of granule cells brainstem: altered serotenergic, noradrenergic and cholinergic systems basal ganglia: normal pre-screening: less invasive, done in the 1st and 2nd trimester diagnostic testing: invasive can pose complications due to taking blood from embryo Pre- screening usually involves a blood test and ultrasound from the mother, if it is the first trimester both blood test and ultrasound, if they are in their second trimester it is only a blood test, if positive results option for Diagnosis of down syndrome diagnostic testing to confirm diagnotic testing includes: amniocentesis: sample of amniotic fluid and then karyotypining done at 14-18 weeks chronic villus sampling: cells are taken from the placenta done at 9-11 weeks precutaneous umbilical blood sampling: blood sample from umbilical cord done at 18-22 weeks (most accurate) there is no cure, cannot come up with a drug that undoes all the developmental changes Treating down syndrome variesd from severity and person physical therapy, speech therapy, occupational therapy, behavioural therapy https://knowt.com/flashcards/e95425ab-0819-467f-9ec1-477cb95acc07?isNew=true 15/15