Postnatal Development of the CNS PDF

Postnatal Development of the CNS Childhood Methods for Nonhuman animals Studying CNS Humans Development o Prenatal o Postnatal Postnatal Brain Development After birth, the brain doubles in volume CNS is not fully mature until late adolescence PF...

Postnatal Development of the CNS Childhood Methods for Nonhuman animals Studying CNS Humans Development o Prenatal o Postnatal Postnatal Brain Development After birth, the brain doubles in volume CNS is not fully mature until late adolescence PFC (prefrontal cortex) is the last region to develop Mostly synaptogenesis, myelination, dendritic branching, axonal growth, neurogenesis* Timeline of Postnatal Brain Development  1. Dendritic branching o parallels pattern of migration. Key o deeper layers migrate first and are first to sprout dendrites Developmental 2. Synaptogenesis Events o Peaks after birth in most brain areas o Primary Visual and Auditory cortex: 4-8 months o PFC: second year 3. Myelination o Roughly parallels functional development o Sensory areas: first few months o Motor areas: soon after sensory areas o PFC: continues into adolescence 4. Regressive changes (pruning) o Periods of synaptic loss/refinement Postnatal Development of the Prefrontal Cortex Relatively slow, more gradual development, continuing into late adolescence Linked to parallel development of “higher” cognitive Self- Organization executive functions monitoring Emotional Emotional Flexible Planning and Planning and Control Control Thinking Prioritizing Prioritizing Impulse Impulse Working Working Task Initiation Control Control Memory Memory  1. Working memory (temporary memory Executive used while a task is being performed) Functions of 2. Planning and carrying out sequences the PFC of action 3. Following rules for social behaviours 4. Context-dependent inhibition of inappropriate responses E.g., error perseveration in 7-12-month- old infants Error Perseveration in 7-12 m.o. Infants: Piaget’s “A not B” Error (video) Geert Stienissen. (2011, Mar 17). Piaget - Stage 1 - Sensorimotor stage : Object Permanence [video]. YouTube. https://youtu.be/NCdLNuP7OA8?si=zMwfB9_q8hkFrnBV  Error Perseveration in 7-12 m.o. Infants: Piaget’s “A not B” Error Perseveration: failure to inhibit original, learned response, which is now incorrect. i.e., The child cannot inhibit the learned response that in the new context has become inappropriate. Aspect of cognitive flexibility requiring PFC. Error Perseveration in 7-12 m.o. Infants: Diamond’s Primate Studies Study with infant and adult rhesus macaques Infant but not adult monkeys made lots of perseverative errors. Adult monkeys with lesions in the prefrontal cortex made the same level of preservative errors as infants (Diamond & Goldman-Rakic, 1991). Error Perseveration in Adults: Wisconsin Card Sorting Test Test for frontal lobe function in adults Participant draws one card at a time and sorts them Experimenter says whether the participant is correct, but does not share the rule Patient guesses the sorting rule (e.g. color) Experimenter changes the rule (e.g. shape) Patients with frontal lobe damage cannot adjust and perform more perseveration errors (keep sorting according to the old rule) Copyright © 2018 Pearson Education, Inc. Experience and Neurodevelopment  Type of experience 1. Permissive experience Key Features 2. Instructive experience of Experiences Timing of experience 1. Critical period 2. Sensitive period Early Studies of Experience and Neurodevelopment Neurons and synapses that are not activated by experience do not usually survive. (Use it or lose it.) Studies on early sensory deprivation / enrichment 1. Animals reared in the dark: vision problems and fewer synapses in visual cortex 2. Rats reared in an enriched environment: various effects on brain structure and function; thicker cortices, more synapses, more dendritic spines 3. Babies with congenital bilateral cataracts: rapidly improve their vision post- removal (age 1-9 mo) but retain some deficits two years later Experience and Neurodevelopment can Compete Antonini and Stryker (1993) Blindfold both eyes → Cortical degeneration Blindfold one eye → Accelerated cortical degeneration Other Direct Effects of Experience on Neurodevelopment (1) Ferrets Roe et al. (1993) Retinal ganglion axons → medial (auditory) geniculate nucleus Inputs from visual system → Auditory cortex became organized like visual cortex Other Direct Effects of Experience on Neurodevelopment (2) Barn Owls Knudsen & Knudsen (1990) Raised with vision displacing (by 23o) prisms on their eyes Both visual and auditory cortex developed with 23-degree spatial shift. Other Direct Effects of Experience on Neurodevelopment (3) Ferrets Li et al. (2017) Neonatal optic nerve activity disturbed before eye opening Disruption of spontaneous firing → Disruption of orientation and direction selectivity in visual cortex Other Direct Effects of Experience on Neurodevelopment (4) MRI study with humans Margulis et al. (2009) Early music training expands the area of the auditory cortex for complex tones. See also: Pantev & Herholz (2011)  1. Direct gene regulation (e.g., for cell adhesion molecules involved in cell adhesion and migration) Possible 2. Regulation of neurotrophin release: post- Mechanisms synaptic release affects pre-synaptic survival. 3. Regulation of spontaneously active neural circuits 4. Effects of specific neurotransmitters on development Postnatal Development of the CNS Adolescence  High novelty-seeking High risk-taking Adolescent High sensation-seeking Behaviour Highly sensitive to peer influence Impulsivity? Not entirely (Dobbs, 2011; Romer et al., 2017) The Adolescent Brain Massive Reorganization During Adolescence Age 12-25 Axonal branching and axonal pruning Progressively increasing axonal myelination … which means? Faster axonal transmission Dendritic branching and dendritic pruning Synapses: strengthening of used, loss of unused  More blue = Reducing gray matter density Time-lapse of brain development Gogtay et al. (2004). Proc. Nat. Acad. Sci., 101: 8174. https://doi.org/10.1073/pnas.0402680101 Massive Reorganization: The Result Overall thinning of the cortex Progressive thickening of the corpus callosum Enhanced frontal-temporal connections Direction of changes: posterior → anterior Understanding Adolescence G. Stanley Hall: Replicates earlier, less civilized, stages of human development. Sigmund Freud: Psychosexual conflict. Erik Erikson: The most tumultuous of life’s several identity crises. More recent: adolescents act oddly because their brains aren’t “done”: a work in progress. Neuronal gawkiness = physical awkwardness  Adolescence is characterized by adaptive changes, new learning, useful Current experiences, developing social skills... Understanding Overall, help them branch out and gain of Adolescence independence.  Novelty-seeking: new experiences & new Adolescent learning Behaviour Risk-taking: not due to undervaluation of risk Normal recognition of their own mortality Revisited Over-, not under-, estimation of risk Differently weigh risk vs reward (adolescents value reward more than adults) (e.g., Freeman et al., 2020) Peer influence: development of social behavior Develop social skills and bonds Seek peer approval Enhanced peer competition “Wean” from parents, project towards others Neurobiological Correlates of Adolescent Behaviour Enhanced sensitivity to dopamine “This long, slow, back-to-front developmental wave, completed Enhanced sensitivity to oxytocin only in the mid-20s, appears to be a Increasingly more sensitive receptors for both uniquely human adaptation. It may be one of our most consequential. High dendritic and synaptic remodeling: greater plasticity and flexibility when needed most “It can seem a bit crazy that we humans don't wise up a bit earlier in High myelination reduces axonal branching and life. But if we smartened up the making of new synapses: reduced plasticity sooner, we'd end up dumber.” Adolescence sets the crucial brain David Dobbs, 2011 David Dobbs, 2011 connectivity for later in life Postnatal Development of the CNS Adulthood  Adult brains retain a high degree of plasticity 1. Neurogenesis Neuroplasticity 2. Experience-induced cortical reorganization in Adults 1. Neurogenesis in Adults Discovery of Adult Neurogenesis Before the 1980s, it was thought that all neurons were produced during embryogenesis Fernando Nottebohm (1983): neuroplasticity and neurogenesis in adult animals (song birds) Since the 80s → several other species rats, mice, primates, humans… Two Primary Regions of Adult Neurogenesis) Maintenance and Replacement in the Olfactory Bulb Subventricular zone Neural stem cells divide to produce New stem cells Neuroblasts → glia-mediated migration → olfactory bulb → mature into interneurons Growth of the Dentate Gyrus Subgranular zone Neural stem cells divide to produce New stem cells Neuroblasts → mature into granule cells of the DG Function for learning and memory? Increases due to e.g., environmental enrichment, exercise However – most new cells die (enter apoptosis) Neurogenesis in the adult hippocampal dentate gyrus. 1. Proliferation and fate determination: Stem cells (beige) in the subgranular zone of the dentate gyrus give rise to transit amplifying cells that differentiate into immature neurons. 2. Migration: Immature neurons migrate into the granule cell layer of the dentate gyrus. 3. Integration: Immature neurons mature into new granule neurons, receive inputs from the entorhinal cortex, and extend projections into CA3 (adapted from Lie et al., 2004).  1. Form new memories Function of 2. Update old memories with new Neurogenesis information in Adults 3. Pattern separation (distinction between different memories) 4. Regulation of mood and anxiety 5. Adapt to complex environments Factors Promoting Adult Neurogenesis INTRINSIC FACTORS EXTRINSIC FACTORS Hormones Environmental enrichment Injury* Social interaction Neurotransmitters Physical activity Neurotrophins Diet Aging Sleep Stress* See also: Hussain et al., 2024; Jiang et al., 2023; Zhao et al., 2024 Experience-induced Cortical Reorganization Experience causes reorganization of sensory and motor maps 1. Tinnitus 2. Violinists: Enlarged hand area in contralateral somatosensory cortex 3. London taxi drivers: Enlarged hippocampus However, these are all correlational… More Direct Evidence for Cortical Reorganization 4. Phantom limb sensations: Somatosensory cortex reorganization, “invasion” by adjacent areas (see Makin & Flor, 2020) 5. Ocular dominance columns in mice: When one eye blindfolded, the other eye becomes more represented in the binocular area (Hofer et al., 2005, see also Hofer et al., 2009; Rose et al., 2009; Jaepel et al., 2017) Potential Use of Cortical Reorganization? Possibly, especially to recover from brain damage (e.g., stroke) Almost no evidence for enhancing/preserving cognitive decline due to aging In healthy adults, some evidence for beneficial effects on working memory and long-term memory, but may be limited to task-specific performance (see Soveri et al., 2017 and Matsuzaki et al., 2023) Glia Support Neuroplasticity Not only do they supply neurotrophins, produce and store neurotransmitters, and supply neurons with nutrients… Recent studies have shown that astrocytes interact with oligodendrocytes to modulate nodes of Ranvier By thinning/thickening the myelin sheath and/or narrowing/widening the node, astrocytes control speed of axonal transmission to coordinate neuronal firing Dutta et al., 2018  15. Shan et al. (2021). Figure 2. Front. Cell Dev. Biol., 9: 680301. https://doi.org/10.3389/fcell.2021.680301 16. Thomason et al. (2017). Figure 1. Sci. Rep., 7: 39286. https://doi.org/10.1038/srep39286 17. Fan et al. (2018). Figure 6. Cell Res., 28: 737. https://doi.org/10.1038/s41422-018-0053- 3 Image 18. Carlyle et al. (2017). Figure 5. Nature Neuroscience, 20: 1792. https://doi.org/10.1038/s41593-017-0011-2 References 19. Smithsonian Institution (2024). Human Characteristics: Brains. https://humanorigins.si.edu/human-characteristics/brains (cont’d) 20. 21. Kadosh et al. (2021). Figure 1. Nutrients, 13: 199. https://doi.org/10.3390/nu13010199 Serres (2018). Slide 14. Adults: Discover your role in child development! Insights from Neuroscience [Translated]. https://www.gironde.fr/sites/default/files/2018- 11/p%C3%A9dagogie%20et%20recherche_Bordeaux_JSERRES(28).pdf 22. Ahmed, R. (2018). The Rhesus monkey is one of the most common species of wildlife found in Pakistan. Wikimedia Commons. https://commons.wikimedia.org/wiki/File:A_Rhesus_monkey_mother_and_infant.jpg 23. Steinberg (2007). Figure 1. Curr. Dir. Psychol. Sci., 16: 56. https://doi.org/10.1111/j.1467- 8721.2007.00475.x 24. Cahana, K., in: Dobbs (2011). Beautiful Brains, National Geographic. http://ngm.nationalgeographic.com/2011/10/teenage-brains/dobbs-text 25. Frankland & Miller (2008). Figure 1. Nature Neuroscience, 11: 1125. https://doi.org/10.1038/nn1008-1124 26. O’Keefe (2013), in: Akst (2015). The Scientist. https://www.the- scientist.com/infographics/neurogenesis-in-the-mammalian-brain-34731 27. Makin & Flor (2020). Figure 3. Neuroimage, 218: 116943. https://doi.org/10.1016%2Fj.neuroimage.2020.116943