Developmental plasticity: Pruning Contents ● ● ● ● ● Developmental plasticity Pruning Receptors Critical periods Article studies Developmental plasticity Plasticity - the adaptive changes in functional brain organization ● adolescent brain copes with one’s environment ○ ● ● immediately -> years lots of connections and high plasticity in child’s brain ○ ● skills, sensory input room for development vs. not that much skill development by pruning connections Pruning ● apoptosis (programmed cell death) reflects competition for trophic factors (neurotrophins) and produces the proper match in the number of presynaptic and postsynaptic neurons ● ● synaptic capacity declines as the neurons mature synaptic rearrengement (Hebbian modifications) 1. neurons that fire together wire together 2. neurons that fire out of sync lose their link NMDA & AMPA receptors Neurons that fire together wire together ● But why? NMDA receptors open only with synaptic coactivation AMPA receptors do not require coactivation NMDA activation changes the amount of AMPA receptors ● the more activation the more receptors Long term potentiation: results from lots of coactivation Long term depression: results from little coactivation Critical period ● a property of brain development is more sensitive during a fixed period of time ○ ○ ○ ● examples of critical periods ○ ○ ○ ● certain skills are easier to learn during critical periods certain development also occurs during critical periods intercellular communications and synaptic activity alter cell’s fate language during the first few years (Friederici 2002, Snow 1978) vision during postnatal development ocular dominance (first six weeks for macaque) why critical periods end ○ ○ ○ plasticity diminishes when axon growth stops plasticity diminishes when properties of synaptic receptors change plasticity diminishes when cortical activation is constrained ■ activity doesn’t activate receptors anymore Loss in Gray Matter (GM) density over time (Gogtay et al., 2004) The GM density on MRI is an indirect measure of a complex architecture of glia, vasculature, and neurons with dendritic and synaptic processes. Studies of GM maturation show a loss in cortical GM density over time, which temporally correlates with postmortem findings of increased synaptic pruning during adolescence and early adulthood. The primary cause for loss of GM density is unknown. It may be driven at least partially by the process of synaptic pruning, together with trophic glial and vascular changes and or cell shrinkage. Brain maturation Higher-order association cortices mature only after lower-order somatosensory and visual cortices, the functions of which they integrate, are developed. Phylogenetically older brain areas mature earlier than newer ones. Alterations either in degree or timing of basic maturational pattern may at least partially be underlying these neurodevelopmental disorders such as childhood-onset schizophrenia or autism. Glial Control of Neuronal Development (Freeman et al.,2006) Glial cells function as important regulators of nervous system development. ● ● ● They provide trophic support to neurons, modulate axon pathfinding, and drive nerve fasciculation. They regulate the number of neurons at early developmental stages by dynamically influencing neural precursor divisions, and at later stages by promoting neuronal cell death through engulfment. Glia also participate in the fine sculpting of neuronal connections by pruning excess axonal projections, shaping dendritic spines, and secreting multiple factors that promote synapse formation and functional maturation. Though glial cells are emerging as essential participants in nervous system morphogenesis, it remains unclear whether glial cells act instructively, or simply respond to neuronal developmental programs. Do glia influence which axons will be pruned? Could glial cells promote neurodegenerative disease by inappropriately pruning axons? Questions?