🧢Neuroscience Unit 6 – Neurodevelopment and Plasticity

Key Concepts and Terminology

• Neurogenesis process of generating new neurons from neural stem cells and progenitor cells
• Synaptogenesis formation of synapses between neurons allowing for communication and signal transmission
• Myelination insulation of axons with myelin sheaths produced by oligodendrocytes (CNS) and Schwann cells (PNS) enhancing signal conduction
• Apoptosis programmed cell death crucial for eliminating unnecessary or dysfunctional cells during development
• Neurotrophic factors proteins that support the growth, survival, and differentiation of neurons (nerve growth factor, brain-derived neurotrophic factor)
• Plasticity ability of the brain to modify its structure and function in response to experiences, learning, and environmental stimuli
• Critical periods specific time windows during development when the brain is highly sensitive to certain experiences and environmental influences
• Epigenetics modifications to gene expression without altering the underlying DNA sequence influencing neurodevelopment and plasticity

Stages of Neural Development

• Neural induction formation of the neural plate from the ectoderm induced by signals from the notochord and mesoderm
• Neurulation folding of the neural plate to form the neural tube the precursor to the central nervous system (brain and spinal cord)
  • Primary neurulation formation of the brain and most of the spinal cord
  • Secondary neurulation formation of the caudal end of the spinal cord
• Neural crest migration multipotent cells that migrate from the neural tube and give rise to various cell types (sensory neurons, autonomic neurons, Schwann cells)
• Proliferation rapid division of neural stem cells and progenitor cells to generate a large pool of neurons and glial cells
• Differentiation process by which neural stem cells and progenitor cells become specialized into specific types of neurons and glial cells
  • Neuronal differentiation guided by transcription factors and signaling pathways
  • Glial differentiation formation of astrocytes, oligodendrocytes, and microglia
• Axon guidance growth and navigation of axons towards their target cells mediated by attractive and repulsive cues (netrins, semaphorins, ephrins)
• Synapse formation establishment of functional connections between neurons involving pre- and postsynaptic specializations

Cellular and Molecular Mechanisms

• Cell fate determination process by which neural stem cells and progenitor cells commit to specific lineages (neurons, astrocytes, oligodendrocytes)
  • Intrinsic factors transcription factors and epigenetic modifications that regulate gene expression
  • Extrinsic factors signaling molecules and growth factors from the extracellular environment
• Neuronal migration movement of newly generated neurons from their site of origin to their final destination in the brain
  • Radial migration neurons migrate along radial glial fibers perpendicular to the ventricular surface (cortical layers)
  • Tangential migration neurons migrate parallel to the ventricular surface (interneurons)
• Axon guidance cues attractive and repulsive molecules that guide axon growth and navigation (netrins, semaphorins, ephrins)
  • Growth cone dynamic structure at the tip of the axon that senses and responds to guidance cues
• Synapse formation assembly of pre- and postsynaptic specializations mediated by cell adhesion molecules and signaling pathways
  • Presynaptic terminal contains synaptic vesicles filled with neurotransmitters
  • Postsynaptic density contains neurotransmitter receptors and signaling molecules
• Neurotransmitter synthesis and release production and release of chemical messengers that mediate synaptic transmission (glutamate, GABA, dopamine)
• Synaptic plasticity strengthening or weakening of synaptic connections in response to neural activity and experience
  • Long-term potentiation (LTP) persistent increase in synaptic strength
  • Long-term depression (LTD) persistent decrease in synaptic strength

Brain Plasticity and Adaptability

• Experience-dependent plasticity modifications in brain structure and function driven by sensory, motor, and cognitive experiences
  • Synaptic pruning elimination of unused or inefficient synapses refining neural circuits
  • Dendritic remodeling changes in the morphology and complexity of dendritic arbors in response to experience
• Learning and memory formation of new neural connections and strengthening of existing ones underlying the acquisition and retention of information
  • Hebbian plasticity "neurons that fire together, wire together" simultaneous activation of pre- and postsynaptic neurons strengthens their connection
• Compensatory plasticity reorganization of neural circuits to compensate for injury, disease, or sensory deprivation
  • Cross-modal plasticity recruitment of brain areas typically associated with one sensory modality to process information from another modality (visual cortex processing tactile information in blind individuals)
• Adult neurogenesis generation of new neurons in specific regions of the adult brain (hippocampus, subventricular zone)
  • Contributes to learning, memory, and mood regulation
  • Influenced by factors such as exercise, environmental enrichment, and stress
• Rehabilitation and recovery harnessing brain plasticity to promote functional recovery after brain injury or stroke
  • Constraint-induced movement therapy (CIMT) encouraging the use of the affected limb by restraining the unaffected one
  • Cognitive rehabilitation training exercises to improve memory, attention, and executive functions

Environmental Influences on Neurodevelopment

• Sensory experience exposure to visual, auditory, and tactile stimuli shapes the development and refinement of sensory systems
  • Monocular deprivation during the critical period can lead to permanent changes in ocular dominance columns in the visual cortex
  • Enriched environments with complex stimuli and social interaction promote synaptic plasticity and cognitive development
• Nutrition adequate intake of essential nutrients (protein, iron, folate, iodine) is crucial for proper brain development
  • Malnutrition during early life can lead to impaired cognitive function and increased risk of neurodevelopmental disorders
• Stress and adversity exposure to chronic stress or adverse experiences (abuse, neglect, poverty) can negatively impact brain development
  • Elevated levels of stress hormones (cortisol) can impair neurogenesis, synaptic plasticity, and cognitive function
  • Supportive caregiving and nurturing environments can buffer the effects of stress and promote resilience
• Toxins and pollutants exposure to environmental toxins (lead, mercury, pesticides) can disrupt neurodevelopment and increase the risk of neurodevelopmental disorders
  • Prenatal alcohol exposure can lead to fetal alcohol spectrum disorders (FASD) characterized by cognitive, behavioral, and physical impairments
• Infections maternal infections during pregnancy (rubella, cytomegalovirus, Zika virus) can interfere with fetal brain development
  • Postnatal infections (meningitis, encephalitis) can cause brain damage and long-term neurological sequelae
• Gene-environment interactions complex interplay between genetic predispositions and environmental factors in shaping brain development and function
  • Certain genetic variants may increase susceptibility to environmental influences (stress, toxins)
  • Epigenetic modifications can mediate the impact of environmental factors on gene expression

Disorders and Abnormalities

• Neurodevelopmental disorders conditions that affect brain development and function, typically manifesting early in life
  • Autism spectrum disorder (ASD) characterized by impairments in social interaction, communication, and restricted or repetitive behaviors
  • Attention-deficit/hyperactivity disorder (ADHD) characterized by inattention, hyperactivity, and impulsivity
  • Intellectual disability significant limitations in intellectual functioning and adaptive behavior
• Genetic disorders neurodevelopmental disorders caused by specific genetic mutations or chromosomal abnormalities
  • Down syndrome caused by an extra copy of chromosome 21, associated with intellectual disability and developmental delays
  • Fragile X syndrome caused by a mutation in the FMR1 gene, associated with intellectual disability, autism, and hyperactivity
• Neurological disorders conditions that affect the structure or function of the nervous system
  • Cerebral palsy group of disorders affecting movement, posture, and coordination, often caused by damage to the developing brain
  • Epilepsy characterized by recurrent seizures due to abnormal electrical activity in the brain
• Psychiatric disorders mental health conditions that can have neurodevelopmental origins or manifestations
  • Schizophrenia characterized by hallucinations, delusions, and disordered thinking, with a typical onset in late adolescence or early adulthood
  • Mood disorders (depression, bipolar disorder) can have early-onset forms and may be influenced by neurodevelopmental factors
• Interventions and therapies approaches to support individuals with neurodevelopmental disorders and promote optimal outcomes
  • Early intervention programs provide targeted support and services to children with developmental delays or disabilities
  • Behavioral therapies (applied behavior analysis, cognitive-behavioral therapy) can help manage symptoms and improve adaptive functioning
  • Pharmacological treatments can be used to address specific symptoms or co-occurring conditions (antipsychotics, stimulants, mood stabilizers)

Research Methods and Techniques

• Animal models use of animal models (rodents, primates) to study neurodevelopmental processes and disorders
  • Transgenic models genetically modified animals that express or lack specific genes related to neurodevelopment
  • Environmental models exposure of animals to specific environmental factors (stress, toxins, infections) to study their impact on brain development
• Neuroimaging techniques non-invasive methods to visualize brain structure and function
  • Magnetic resonance imaging (MRI) provides detailed images of brain anatomy and can track structural changes over time
  • Functional MRI (fMRI) measures changes in blood flow and oxygenation related to neural activity during specific tasks or stimuli
  • Diffusion tensor imaging (DTI) maps the diffusion of water molecules in brain tissue, allowing for the visualization of white matter tracts
• Electrophysiology techniques that measure the electrical activity of neurons and neural circuits
  • Electroencephalography (EEG) records the electrical activity of the brain using electrodes placed on the scalp
  • Magnetoencephalography (MEG) measures the magnetic fields generated by electrical activity in the brain
  • Patch-clamp recording measures the electrical currents flowing through individual ion channels in neuronal membranes
• Molecular and genetic techniques methods to study the molecular and genetic basis of neurodevelopment
  • Polymerase chain reaction (PCR) amplifies specific DNA sequences for analysis
  • In situ hybridization detects the presence and localization of specific mRNA sequences in brain tissue
  • Genome-wide association studies (GWAS) identify genetic variants associated with neurodevelopmental disorders
• Computational modeling use of mathematical and computational models to simulate and predict neurodevelopmental processes
  • Neural network models simulate the behavior of interconnected neurons and can be used to study learning and plasticity
  • Biophysical models incorporate the physical and chemical properties of neurons and synapses to study their function
• Longitudinal studies follow individuals over an extended period to track neurodevelopmental trajectories and outcomes
  • Birth cohort studies follow a group of individuals from birth, collecting data on various aspects of their development and environment
  • High-risk studies follow individuals with a higher likelihood of developing a neurodevelopmental disorder (due to genetic or environmental factors)

Applications and Future Directions

• Early intervention and prevention strategies to identify and support individuals at risk for neurodevelopmental disorders
  • Screening programs to detect developmental delays or abnormalities in infants and young children
  • Parent education and support programs to promote nurturing and stimulating environments for child development
• Personalized medicine tailoring interventions and therapies based on an individual's genetic, environmental, and developmental profile
  • Pharmacogenomics using genetic information to guide the selection and dosing of medications
  • Targeted therapies addressing specific molecular pathways or brain circuits involved in neurodevelopmental disorders
• Stem cell therapies use of stem cells to replace or regenerate damaged or dysfunctional neural tissue
  • Neural stem cell transplantation delivering neural stem cells to specific brain regions to promote repair and regeneration
  • Induced pluripotent stem cells (iPSCs) generating patient-specific stem cells from adult somatic cells for disease modeling and drug screening
• Neuromodulation techniques non-invasive methods to modulate brain activity and plasticity
  • Transcranial magnetic stimulation (TMS) uses magnetic fields to stimulate or inhibit specific brain regions
  • Transcranial direct current stimulation (tDCS) applies weak electrical currents to modulate neuronal excitability
  • Deep brain stimulation (DBS) involves the surgical implantation of electrodes to stimulate specific brain structures
• Gene therapy introducing functional genes or silencing dysfunctional genes to treat neurodevelopmental disorders
  • Viral vectors (adeno-associated virus, lentivirus) can be used to deliver therapeutic genes to specific brain regions
  • CRISPR-Cas9 a powerful gene-editing tool that can be used to correct genetic mutations or modulate gene expression
• Interdisciplinary collaboration integration of knowledge and approaches from various fields (neuroscience, genetics, psychology, education) to advance the understanding and treatment of neurodevelopmental disorders
  • Translational research bridging the gap between basic science discoveries and clinical applications
  • Community-based participatory research involving stakeholders (families, educators, healthcare providers) in the research process to ensure relevance and impact
• Ethical considerations addressing the ethical implications of neurodevelopmental research and interventions
  • Informed consent ensuring that participants (or their legal representatives) understand the risks and benefits of research participation
  • Privacy and confidentiality protecting the personal information and data of research participants
  • Equitable access ensuring that the benefits of research and interventions are accessible to all individuals, regardless of socioeconomic status or geographic location