Mind & Brain in the What Is Neuroscience? 21 st Century Multidisciplinary research attempts to understand brain function are Dr Guy Sutton collectively referred to as Medical Biology Interactive neuroscience . Aims Neuroscience encompasses • To review how and why brain research has research methodologies from many advanced over the past twenty years. diverse scientific disciplines, including anatomy, biochemistry, biophysics, •To consider particular advances in our understanding of brain function; neuroplasticity, neurogenetics, and pharmacology, philosophy, neuroimaging. physiology, cognitive science and neuropsychology. • To briefly address new technologies, the immediate future and what is on the horizon for brain research. Decade of the Brain Decade of the Brain Kandel & Squire (2000): the main developments in neuroscience were: The U.S. Library of Congress and the National Institute 1) The transition of the study of nerve of Mental Health sponsored development from a descriptive to a this inter-organisational molecular discipline, with advances in our research initiative. understanding of neuroplasticity. The general aim was to raise 2) The start of the long process of mapping the profile of research genes to nerve development, differentiation endeavours and ethical and function in the central nervous system. issues in brain research with 3) The development of functional brain the general public. imaging and its application to the study of human cognition. Nerve Cell Growth & Synaptogenesis Neuroplasticity The majority of neurons comprising the mature brain •Neuroplasticity refers to the develop prenatally and are present from birth. capacity of the nervous system to modify its organisation. Some new neurons develop after birth in areas of the brain such as the hippocampus. •Changes can occur as a consequence The most dramatic changes in the developing of many events, including the normal brain relate to the growth of axons, dendrites, development and maturation of the and the number of synaptic connections organism, the acquisition of new skills between neurons, a process known as (‘learning’) in immature and mature synaptogenesis . organisms, after damage to the nervous system and as a result of sensory Synaptogenesis results in a surplus of synapses in deprivation. the prenatal brain, thus these connections undergo ‘pruning’, a form of neural ‘fine tuning’.
Experience-Dependent Structural Neuroplasticity & The Ageing Brain Plasticity Our mental faculties do not deteriorate In academic mathematicians, cortical as quickly as we sometimes think. gray matter density in the left inferior frontal lobe and bilateral inferior parietal Myths: lobules were significantly increased •the adult brain is incapable of change relative to controls. •the adult brain suffers increasing neural Increases in gray matter in the right loss with consequent deterioration in inferior parietal lobule in mathematicians learning, memory and performance was strongly correlated with duration of time as an academic. •frontal lobe structure and development is effectively finalised by adolescence Aydin, K. et al (2007). Increased gray matter density in the parietal cortex of mathematicians: a voxel-based morphometry study. American Journal of Neuroradiology , 28: 1859-1864. Neuroplasticity & The Ageing Brain Plasticity & Fast Brain Change • Although laying down new Sensory and motor areas of the adult brain information becomes less efficient can adapt very quickly. with age, there seems to be no age limit for learning. In a mere five days, the motor cortex , • Neuroplasticity depends critically responsible for movement of body parts (fingers on how much the brain is used. 'Use it included) increased in size and activity when - or lose it' is therefore good advice. non-pianist adults learnt a five-finger piano exercise for two hours per day over a five-day • Evidence from neuroscience that period. Control participants experience no such educational rehabilitation in adulthood change. is not only possible but well worth investing in. Pascual-Leone, A. (2001). The brain that plays music and is changed by it. Annals of the New York Academy of Sciences , 930: 315-329. Addiction: A Loss of Plasticity of the Brain? Addiction: A Loss of Plasticity of the Brain? • Why is it that only some drug users • Chronic exposure to drugs causes many become addicts? The transition to modifications to the physiology of the brain. addiction could result from a persistent Which of these modifications is responsible for the impairment of synaptic plasticity in a key development of an addiction? structure of the brain. • Animals which developed an addiction to • Addiction may result from a form of cocaine exhibit a permanent loss of the anaplasticity , i.e. from incapacity of capacity to produce a form of plasticity known addicted individuals to counteract the as long term depression (or LTD). It plays a pathological modifications caused by the major role in the ability to develop new drug to all users. memory traces and, flexible behaviour. Fernando Kasanetz, V. et a l (2010). Transition to Addiction is Associated with a Persistent Fernando Kasanetz, V. et a l (2010). Transition to Addiction is Associated with a Persistent Impairment in Synaptic Plasticity. Science , June 24, DOI: 10.1126/science.1187801 Impairment in Synaptic Plasticity. Science , June 24, 2010 DOI: 10.1126/science.1187801
Genes & The Nervous System Genes In Brain Development What Do Genes Do In The Brain? A number of gene families play a role in the control of CNS development in • supervise the construction of neurotransmitters, vertebrates. Many of these genes are receptors, enzymes and the like homeobox genes. • supervise the metabolism of glucose The most well- known and best-studied • guide the specialisation and among them are the Hox genes which migration of cells in addition to the control regionalisation and cell identity initial pattern of neural wiring in the developing hindbrain and spinal cord. • supervise the maintenance of synapses, altering the wiring of the brain BERT & ERNI Proteins Control Brain Development Hox Genes & Neuron Pathways Two proteins, BERT and ERNI, interact in embryos Pontine neurons are generated in to control when different organ systems in the the rear part of the brain and body start to form. ultimately end up in the cerebellum. In vertebrate embryos a few hours old, a sequence of reactions occurs preventing early Pontine neuron migration is controlled development of neural cells, conveying a head by specific Hox genes. Knocking out start to other cells and preventing premature NS the expression of the Hoxa2 gene development. changes the path of the neurons, causing them to end up in the wrong At the crucial time, BERT binds with the protein ERNI part of the brain. and other proteins to unblock a gene called Sox2, which gives the green light to cells to start forming the brain and nervous system. Geisen, L. et al (2008). Hox Paralog Group 2 Genes Control the Migration of Mouse Pontine Neurons through Slit-Robo Signaling. PLoS Biology , 2008; 6 (6): e142 DOI: Papanayotou, C. et al (2008). A mechanism regulating the onset of Sox2 expression in the 10.1371/journal.pbio.0060142. embryonic neural plate. PLoS Biology, 6(1): e2.doi:10.1371/journal.pbio.0060002. A Master Gene For Human Brain Development Neurons Developed from Stem Cells Successfully Wired With Other Brain Regions in Animals • A single gene, Pax6 , has been identified Transplanted neurons grown that seems to be a master regulator of from embryonic stem cells were human brain development, instructing fully integrated into the brains of stem cells at the earliest stages of young animals. embryonic development to become the cells of the brain and spinal cord. This new finding is the first to show that stem cells can be directed not only to become specific brain • In human, but not lower animal brain cells – those that are damaged in development, Pax-6 plays a very spinal cord injury - but to link important role, particularly in cortical correctly. development. Ideguchi, M. et al (2010). Murine Embryonic Stem Cell-Derived Pyramidal Neurons Integrate into the Cerebral Cortex and Appropriately Project Axons to Subcortical Targets. The Journal Xiaoqing Zhang, C. T. et al (2010). Pax6 Is a Human Neuroectoderm Cell Fate Determinant. Stem of Neuroscience, January 20, 2010, 30(3):894-904; doi:10.1523/JNEUROSCI.4318-09.2010 Cel l, 7, 1, 90-100, 2 July 2010 DOI: 10.1016/j.stem.2010.04.017
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