Biopsych lecture 5 development & plasticity.pptx

Biological Psychology Development of the Nervous System; Brain Injury & Plasticity Dr Elaine H. Niven Overview Week 1 EN Overview & Comparative Cognition 1 Week 2 EN Comparative Cognition 2 Week 3 EN Structure & Function Week 4 EN The Neurobiology of Memory & Classic Cases Week 5 EN Development...

Biological Psychology Development of the Nervous System; Brain Injury & Plasticity Dr Elaine H. Niven Overview Week 1 EN Overview & Comparative Cognition 1 Week 2 EN Comparative Cognition 2 Week 3 EN Structure & Function Week 4 EN The Neurobiology of Memory & Classic Cases Week 5 EN Development of the Nervous System; Brain Injury & Plasticity Week 6 Week 7 Week 8 Rhythms Week 9 Week 10 BS Sensorimotor Systems BS Biopsychology of: Hunger & Eating BS Biopsychology of: Sleep, Dreaming & Circadian BS Biopsychology of: Addiction & Reward BS Biopsychology of: Health & Stress • Conceptual understanding that: • the brain develops throughout lifetime • experience is key • there are restrictions on changes • Neurodevelopment: • Describe the 5 phases of neurodevelopment • Link embryonic development to adult brain structure • Adult plasticity: • discuss neural reorganization • Potential and limits of recovery of function after brain damage Aims and learning outcomes • Following lecture, proceed with reading to be able to identify and explain, with examples: • Experiences affecting early postnatal development (emphasis should be on genetic-environmental interactions) • Experiences affecting adult plasticity Aims and learning outcomes • Ovum + Sperm = Zygote • Developing neurons accomplish these things in five phases. • • • • • Induction of the neural plate Occur in Neural proliferation sequence Migration and aggregation Axon growth and synapse formation Neuron death and synapse rearrangement Extended & overlapping Phases of neurodevelopment • Ovum + Sperm = Zygote • Developing neurons accomplish these things in five phases. • • • • • Induction of the neural plate Neural proliferation Migration and aggregation Axon growth and synapse formation Neuron death and synapse rearrangement Phases of neurodevelopment • A patch of tissue on the dorsal surface of the embryo becomes the neural plate. • Development is induced by chemical signals from the mesoderm (the “organizer”). • Starts approx 18 days after gestation Induction of the Neural Plate • Totipotent: the earliest cells have the ability to become any type of body cell. • Pluripotent: can give rise to many types of body cell • Neural plate cells are often referred to as embryonic stem cells. • Have Unlimited Capacity for Self-Renewal • Can Become Any Kind of Mature Cell • Multipotent: with development, neural plate cells are limited to becoming one of the range of mature nervous system cells. Induction of the Neural Plate • Neural Tube forms basis of future spinal cord and brain (CNS) • Neural Crest forms basis of future PNS Induction of the Neural Plate • Approximately 40 days: tissue which develops into CNS (neural tube) is recognizable as fluid filled (cerebral ventricles) tube Neural tube cells proliferate in species-specific ways Differentiation and maturation of cells result in development of specific characteristics Three swellings at the anterior end in humans will become the forebrain, midbrain, and hindbrain. These major structures develop into fully formed brain Neural Proliferation Animation of development in action: • QUIZ YOURSELF ! • WHAT STRUCTURES MAKE UP THE HINDBRAIN? • Medulla; Pons; Cerebellum • WHAT STRUCTURES MAKE UP THE MIDBRAIN? • Reticular formation; tectum (superior & inferior colliculi); substantia nigra • WHAT STRUCTURES MAKE UP THE FOREBRAIN? • (among others) thalamus; hypothalamus; cerebral cortex • Approximately 40 days: tissue which develops into CNS (neural tube) is recognizable as fluid filled (cerebral ventricles) tube Neural tube cells proliferate in species-specific ways Differentiation and maturation of cells result in development of specific characteristics Three swellings at the anterior end in humans will become the forebrain, midbrain, and hindbrain. These major structures develop into fully formed brain Neural Proliferation Animation of development in action: • Migrating cells are immature, lacking axons and dendrites. • Two types of neural tube migration • Radial migration (moving out): usually by moving along radial glial cells • Tangential migration (moving up) • Two methods of migration • Somal: an extension develops that leads migration; the cell body follows • Glial-mediated migration: the cell moves along a radial glial network • Most cells engage in both types of migration. Migration & Aggregation • Neural Crest (PNS) Migration: • Experimental evidence (transplanted cells) for migration as guided by chemical signals • Gilal cells involved in release of chemical signals Migration & Aggregation • After migration, cells align themselves with other cells and form structures. • Cell-Adhesion Molecules (CAMs) • Aid both migration and aggregation • CAMs recognize and adhere to molecules. • Gap junctions pass cytoplasm between cells. • Prevalent in brain development • May play a role in aggregation and other processes Migration & Aggregation • Once migration is complete and structures have formed (aggregation), axons and dendrites begin to grow. • Growth cone: at the growing tip of each extension; extends and retracts filopodia as if finding its way Growth cones. The cytoplasmic fingers (the filopodia) of growth cones seem to grope for the correct route. (Courtesy of Naweed I. Syed, Ph.D., Departments of Anatomy and Medical Physiology, the University of Calgary.) Axon Growth and Synapse Formation Sperry 1940: First demonstration that axons are capable of precise growth o Rotating frogs eyes or severing nerve AND rotating eye = same behavior o Strong behavioural evidence that retinal ganglion cell grows back to same point on optic tectum Sperry, 1963: Chemoaffinity Hypothesis • Postsynaptic surfaces release specific chemicals labels which attract target • Mechanisms underlying axonal growth are the same across species. • A series of chemical signals exist along the way, attracting and repelling. • Guidance molecules are often released by glia; adjacent growing axons also provide signals. • Pioneer growth cones: the first to travel a route; interact with guidance molecules • Fasciculation: the tendency of developing axons to grow along the paths established by preceding axons Axon Growth and Synapse Formation (Con’t) • Topographic gradient hypothesis of axonal migration (e.g. Flanagan, 2006) - seeks to explain topographic maps; axon targets are arranged in the same way on the terminal surface as they are on the original surface - Growing axons are guided to their target by two intersecting chemical gradients - Each point of retina is represented by different combinations of concentrations • Formation of new synapses depends on the presence of glial cells—especially astrocytes. • High levels of cholesterol are needed—and are supplied by astrocytes. • Chemical signal exchange between pre- and postsynaptic neurons is needed. • A variety of signals act on developing neurons. Axon Growth and Synapse Formation • Approximately 50 percent more neurons than are needed are produced; death is normal. • Both Passive Cell Death (Necrosis) and Active Cell Death (Apoptosis) • Apoptosis is safer than necrosis because it does not promote inflammation. Neuron Death and Synapse Rearrangement • Neurotrophins promote growth and survival, guide axons, and stimulate synaptogenesis. • E.g. Nerve growth factor (NGF) • Neurons die due to failure to compete for chemicals provided by targets. • The more targets, the fewer cell deaths • Destroying some cells increases the survival rate of remaining cells. • Increasing the number of innervating axons decreases the proportion that survive. Neuron Death and Synapse Rearrangement • Neurons that fail to establish correct connections are particularly likely to die. • Space left after apoptosis is filled by sprouting axon terminals of surviving neurons. • Refinement of connections • This ultimately leads to increased selectivity of transmission. Neuron Death and Synapse Rearrangement • Postnatal growth is a consequence of: • Synaptogenesis • Myelination of sensory areas and then motor areas: myelination of prefrontal cortex continues into adolescence. • Increased dendritic branches • Overproduction of synapses may underlie the greater plasticity of the young brain. Postnatal Cerebral Development in Human Infants • Believed to Underlie Age-Related Changes in Cognitive Function • No single theory explains the function of this area. • Prefrontal cortex plays a role in working memory, planning and carrying out sequences of Development actions, and Cortex inhibiting inappropriate of the Prefrontal • Permissive experiences: those that are necessary for information in genetic programs to be manifested • Instructive experiences: those that contribute to the direction of development • Effects of experience on development are time-dependent. • Critical period • Sensitive period Effects of Experience on the Early Development, Maintenance, and Reorganization of Neural Circuits Case study: Birdsong • Songbirds (4000+ species) produce 2 classifications of vocalizations: calls & songs • Songs consist of temporally isolated discrete elements (notes, syllables) ordered in species-typical ways. • Ontogenetically: human speech & birdsong have parallels • As with human language: based on capacity for vocal learning with reference to auditory feedback • • • • • Highly specialized behaviourally and neurally Learn complex sequences early (sensitive periods) Sensory experience shapes vocal output (sensorimotor learning) Auditory feedback from self-generated vocalizations necessary Innate dispositions for learning correct sounds & sequences Bolhuis, J.J., Okanoya, K. & Scharff, C. (2010) Twitter evolution: converging mechanisms in birdsong and human speech. Nature Reviews Neuroscience, 11, 747-759. Birdsong: song control nuclei Bolhuis, J.J., Okanoya, K. & Scharff, C. (2010) Twitter evolution: converging mechanisms in birdsong and human speech. Nature Reviews Neuroscience, 11, 747-759. Birdsong: stages Normal development Sensitive Period/memorization phase: Initial exposure to tutor. Song becomes stored model. Silent Period (can be months in duration) Subsong period Practice without communication. Quiet, initially formless. error refinement to species-specific form: Plastic song Trial-and- Song crystallization Adult version: permanent form, developed repetoire May use only a fraction of elements first learned & practiced Bolhuis, J.J., Okanoya, K. & Scharff, C. (2010) Twitter evolution: converging mechanisms in birdsong and human speech. Nature Reviews Neuroscience, 11, 747-759. Reared in isolation; no exposure to tutor: sing abnormal songs in subsong period, development/refinement occurs -> stereotyped, species-typical characteristics Deafened birds after sensitive period: post-sensory phase shows abnormal song, abnormal vocalizations Deafened birds after crystalized song: normal singing Birdsong: manipulation Bolhuis, J.J., Okanoya, K. & Scharff, C. (2010) Twitter evolution: converging mechanisms in birdsong and human speech. Nature Reviews Neuroscience, 11, 747-759. • Early Visual Deprivation • Fewer synapses and dendritic spines in primary visual cortex • Deficits in depth and pattern vision • Enriched Environment • Thicker cortexes • Greater dendritic development • More synapses per neuron Early Studies of Experience and Neurodevelopment • Ocular Dominance Columns Example: - Monocular deprivation changes the pattern of synaptic input into layer IV of V1 (but not binocular deprivation). - Altered exposure during a sensitive period leads to reorganization. Active motor neurons take precedence over inactive ones. Competitive Nature of Experience and Neurodevelopment • Some neural circuits are spontaneously active; this activity is needed for normal development. • Neural activity regulates the expression of genes that direct the synthesis of CAMs. • Neural activity influences the release of neurotrophins. Experience Fine-Tunes Neurodevelopment Neuroplasticity in Adults • The mature brain changes and adapts. • Neurogenesis (growth of new neurons) is seen in the olfactory bulbs and hippocampuses of adult mammals: adult neural stem cells created in the ependymal layer lining in ventricles and adjacent tissues. • Enriched environments and exercise can promote neurogenesis. Neuroplasticity in Adults (Courtesy of Carl Ernst and Brian Christie, Department of Psychology, University of British Columbia.) glia new cells neuro n • Synaptogenesis – creation of new synapses and • Long Term Potentiation Facilitation of communication at existing synaptic connections (Week 4) • Remember that: ”cells that fire together wire together” • Increased number of receptors for specific neurotransmitters • Increased number of post-synaptic spines • Increased size of synapses • Tinnitus (ringing in the ears) produces major reorganization of the primary auditory cortex. • Adult musicians who play instruments fingered by the left hand have an enlarged representation of that hand in the right somatosensory cortex. • Skill training leads to reorganization of motor cortex. Effects of Experience on the Reorganization of the Adult Cortex Four main neuroplastic responses to nervous system damage can be characterized: • Degeneration: deterioration • Regeneration: regrowth of damaged neurons • Reorganization • Recovery Neuroplastic Responses to Nervous System Damage - Brain Tumors - Cerebrovascular Disorders - Closed-Head Injuries • Epilepsy • Parkinson’s disease • Huntington’s disease - Infections of the Brain • Multiple sclerosis - Neurotoxins • Alzheimer’s disease - Genetic Factors Causes of Brain Damage & Neurological Diseases • Cutting axons (axotomy) is a common way to study responses to neuronal damage. • Anterograde: degeneration of the distal segment between the cut and synaptic terminals • Cut off from cell’s metabolic center; swells and breaks off within a few days • Retrograde: degeneration of the proximal segment between the cut and cell body • Progresses slowly; if the regenerating axon makes a new synaptic contact, the neuron may survive. Degeneration r e t r o g r a d e cut a n t e r o g r a d e • Does not proceed as successfully in mammals and other higher vertebrates: the capacity for accurate axonal growth is lost in maturity. • Regeneration is virtually nonexistent in the CNS of adult mammals and unlikely, but possible, in the PNS. Neural Regeneration • If the original Schwann cell myelin sheath is intact, regenerating axons may grow through them to their original targets. • If the nerve is severed and the ends are separated, they may grow into incorrect sheaths. • If ends are widely separated, no meaningful regeneration will occur. Neural Regeneration in the PNS • (some) CNS neurons can regenerate if transplanted into the PNS, whereas (some) PNS neurons won’t regenerate in the CNS. • Schwann cells promote regeneration. • Neurotrophic factors stimulate growth. • CAMs provide a pathway. • Oligodendroglia actively inhibit regeneration. Mammal PNS Neurons Regenerate; CNS Don’t • Reorganization of primary sensory and motor systems has been observed in laboratory animals following: • Damage to peripheral nerves • Damage to primary cortical areas • Damage motor neurons controlling e.g. whiskers; vibrissae region in cortex comes to perform other motor control • Studies show that largescale reorganization is Neural Reorganization possible. • Brain-imaging studies indicate that there is continuous competition for cortical space by functional circuits. • E.g., auditory and somatosensory input may be processed in formerly visual areas of the brains of blinded individuals. Cortical Reorganization Following Damage in Humans • Are existing connections strengthened due to a release from inhibition? • Consistent with speed and localized nature of reorganization • Are new connections established? • Magnitude can be too great to be explained by changes in existing connections. Mechanisms of Neural Reorganization • It is difficult to conduct controlled experiments on populations of braindamaged patients. • Researchers cannot distinguish between true recovery and compensatory changes. • Cognitive reserve—education and intelligence—is thought to play an important role in recovery of function; this may permit cognitive tasks to be accomplished in new ways. • Adult neurogenesis may play a role in recovery. Increased neurogenesis in the dentate gyrus following damage. (Note: images not not human sample) Recovery of Function after Brain Damage Applying neuroplasticity to treatment of CNS Damage: • Reducing Brain Damage by Blocking Neurodegeneration • Promoting Recovery by Transplantation • Promoting Recovery by Promoting Regeneration • Promoting Recovery by Rehabilitative Training • Various neurochemicals can block or limit neurodegeneration. • Apoptosis inhibitor protein: introduced in rats via a virus • Neurotrophic factors (BDNF, GDNF) block degeneration of damaged neurons. Reducing Brain Damage by Blocking Neurodegeneration • Transplanting Fetal Tissue • Fetal substantia nigra cells were used to treat MPTP-treated monkeys (PD model). • Treatment was successful. • Limited success with humans • Transplanting Stem Cells • E.g., embryonic stems cells implanted into damaged rat spinal cord • Rats with spinal damage showed improved mobility. Promoting Recovery by Neurotransplantation • While regeneration does not normally occur in the CNS, it can be induced experimentally by directing the growth of axons by Schwann cells. • Neuroprotective molecules also tend to promote regeneration. Promoting CNS Recovery by Promoting Regeneration • Monkeys recovered hand function from induced strokes following rehab training. • Constraint-induced therapy in stroke patients— tying down the functioning limb while training the impaired one—creates a competitive situation to foster recovery. • Facilitated Walking as an Approach to Treating Spinal Injury Promoting Recovery by Rehabilitative Training • Benefits of Cognitive and Physical Exercise • Correlations in human studies between physical/cognitive activity and resistance or recovery from neurological injury and disease • Rodents raised in enriched environments are resistant to induced neurological conditions (epilepsy, models of Alzheimer’s, Huntington’s, etc.). • Physical activity promotes adult neurogenesis in the rodent hippocampus. Promoting Recovery by Rehabilitative Training (Con’t) • Conceptual understanding that: • the brain develops throughout lifetime • experience is key • there are restrictions on changes • Neurodevelopment: • Describe the 5 phases of neurodevelopment • Link embryonic development to adult brain structure • Adult plasticity: • discuss neural reorganization • Potential and limits of recovery of function after brain damage Aims and learning outcomes • Ramachandran’s hypothesis: phantom limb is caused by reorganization of the somato-sensory cortex following amputation. • The amputee feels a touch on his face and also on his phantom limb (due to their proximity on somatosensory cortex). • An amputee with chronic phantom limb pain gets relief through visual feedback: view in mirror of her intact hand unclenching, as seen in mirror box. Phantom Limbs: Neuroplastic Phenomena Reading • Pinel (whatever edition) “Biopsychology” chapters on ‘Development of the Nervous System’ and ‘Brain Damage and Neuroplasticity’ (chapters 9 and 10 in 11th, 10th and 9th Editions) Level 3 required ; MSc suggested: • Section on Birdsong in Shettleworth (page 484-486). Older copies of Pinel also have an interesting section on birdsong (page 70-71 in 10th edition). And again: • Genes to Cognition online: http://www.g2conline.org (for use of 3D brain tool) The Case of Genie (as referenced in development chapter of Pinel): https://www.youtube.com/watch?v=VjZolHCrC8E Siddharthan Chandran TED talk: Can the damaged brain repair itself? • http://www.ted.com/talks/ siddharthan_chandran_can_the_damaged_brain_repair_itself