Neuroplasticity PDF

NEUROPLASTICI TY The Ability to Change  Objectives 1. Define neuroplasticity and give examples. 2. Describe two types of experience- dependent plasticity associated with learning and memory...

NEUROPLASTICI TY The Ability to Change  Objectives 1. Define neuroplasticity and give examples. 2. Describe two types of experience- dependent plasticity associated with learning and memory. 3. Describe the degenerative and regenerative events of axonal injury in the peripheral nervous system (PNS). 4. Compare and contrast central nervous system (CNS) and PNS recovery following injury. 5. Describe excitotoxicity. Copyright © 2018 by Elsevier, Inc. All rights reserved. 3 Neuroplasticity Neuroplasticity The ability of neurons to change their function their chemical profile Types and amounts of neurotransmitters produced their structure Involved in learning, memories and recovery from CNS damage Habituation Habituation Simple form of neuroplasticity A decrease in response to a repeated, harmless stimulus After a period of rest, response returns-short- term and reversible Caused by a decrease in synaptic effectiveness Less excitatory neurotransmitters Less free intracellular Ca++ Examples Tactile defensiveness Vestibular disorders Experience- Dependent Plasticity Learning and Memory Experience-dependent plasticity Persistent, long-term changes between in the strength of synapses or within neural networks fMRI of brain while learning to play instrument show large regions of activation, these become smaller as skill is achieved Requires protein synthesis, growth of new synapses, modification of synapses Repetition of a stimulus or repeated pairing of a presynaptic and postsynaptic firing alters excitability of a neuron and growth (or inhibition) of synapses, especially at dendritic spines Experience-Dependent Plasticity Learning and Memory Mechanisms of Experience Dependent Plasticity Functional changes in ion channels Plasticity at inhibitory GABA synapses Homeostatic plasticity Long term potentiation Long term depression This plasticity is a double-edged sword Plasticity can help form memories but can also aid in the development of chronic pain syndromes Long Term Potentiation/Depression Occurs at excitatory glutaminergic synapses Can occur presynaptically via changes in neurotransmitter release Can occur postsynaptically by changes in receptor density or efficiency Studied extensively in hippocampus and cortex Transcranial magnetic stimulation can change synaptic plasticity via these mechanisms Role of astrocytes-gliotransmitters primarily affect postsynaptic membrane Long-term Potentiation: Structural Changes in Synapse Silent synapses lack functional AMPA receptors in cell membrane, inactive NMDA receptor will bind glutamate and let cations in Long-term Potentiatio n: Structural Changes in Synapse NMDA receptor becomes activated and binds glutamate, permitting influx of calcium ions Long-term Potentiation: Structural Changes in Synapse Increased calcium levels cause AMPA receptors to be inserted into cell membrane from the cytoplasm Calcium enters nucleus and can turn on certain genes Long-term Potentiation: Structural Changes in Synapse Continued stimulation causes the generation of a NEW dendritic spine-a structural change Long-term Potentiation: Structural Changes in Synapse Changes occur in presynaptic cell causing the formation of a new synapse AMPA receptors available for binding glutamate  Long Term Depression (LTD) In LTD, AMPA receptors are removed from the membrane into the cytoplasm and synapse becomes silent Neuronal Recovery from Injury Injury to the cell body causes the death of the neuron, injury to axon causes degeneration Axonal injury Wallerian degeneration Synkinesis Mechanisms of Recovery Synaptic changes Functional Reorganization of Cerebral Cortex Activity Related changes in Neurotransmitter Release Wallerian Degeneration Axonal injury Segments retract Distal Segment Axon terminal degenerates Myelin breaks down Debris cleaned by glia Proximal segment Cell body loses Nissl substance, nucleus is eccentric (central chromatolysis) Presynaptic terminals retract from dying cell body Postsynaptic cells degenerate Axonal Sprouting Axons in PNS easily damaged Regrowth is called axonal sprouting Collateral(A) Regenerative (B) Guided by Schwann cells Bands of Bungner NGF Axonal growth Wallerian Degenerati on and Axonal Regeneratio n PNS Peripheral Nerve Regeneration Synkine sis Motor axons regrow onto different targets (muscles or glands) and cause inintended movements or secretion when neurons fire May adjust with experience Crocodile tears- regrowth of facial nerve axons from muscles that should innervate zygomaticus major into lacrimal gland-cry when asked to smile  Spinal Cord Injury (SCI) Traumatic Brain Injury (TBI) Cascade of events in the days and weeks after injury Axon permeability increases Axonal leading to calcium influx Calcium influx disrupts Injury axonal transport Axons swell in CNS Proximal stump retracts forming axon ball-leads to Wallerian degeneration SCI-damage to fiber tracts ranging from contusion to complete severing TBI-diffuse axonal injury due to shearing forces Lack of CNS Regeneratio n Scar formed by astrocytes and microglia Little NGF Microglia release inflammatory cytokines Oligodendrocytes release NOGO (neurite outgrowth inhibitor) Treatments Drugs or antibodies to inhibit NOGO Stem cells Anti-inflammatories Synaptic Changes Following Axonal Injury Changes in synaptic effectiveness Denervation hypersensitivity Synaptic hypereffectiveness Unmasking of silent synapses  Synaptic Effectiveness Recovery of synapse effectiveness occurs with a reduction in local edema  Denervation Hypersensitivity Destruction of the presynaptic neuron deprives postsynaptic cells of an adequate supply of neurotransmitter neurons destroyed The postsynaptic cell makes new receptors at the remaining terminals  Synaptic Hypereffectiveness Some presynaptic terminals are lost Neurotransmitter accumulates in the undamaged presynaptic terminals, resulting in excessive neurotransmitter release at the  Unmasking Silent Synapses In silent synapses, only NMDA receptors are present on the postsynaptic membrane and synaptic transmission does not occur Movement of AMPA receptors into the postsynaptic membrane Metabolic Effects of Neuronal Damage Neurons deprived of oxygen release glutamate, an excitatory neurotransmitter Binds to NMDA receptors Ca ++ rushes into cell More K + diffuses out Na + K + pump must work harder Increased lactic acid-acidosis can break down cell membrane High intracellular Ca++ causes release of proteases Arachidonic acid leads to inflammation and free radicals Water influx causes cell edema Functional Reorganization of Cortex Reassignment of neuron function in adults following CNS injury SCI-area representing leg replaced by expansion of hand representation Individuals with certain variants of BDNF gene fare worse after CNS damage Clinical Approaches Activity related changes in neurotransmitter release can cause changes in somatosensory cortex Gene Therapy Availability of NGF gene in dopaminergic neurons can rescue these cells from degeneration Neurogenesis Neuronal precursors migrate towards ischemic areas after stroke(often don’t survive due to inflammation) Metabolic Effects of Neuronal Damage Excitotoxicity Cell death caused by overexcitation of neurons Seen after stroke, TBI, neurodegenerative diseases Expands the area of functional damage/losses Mechanisms Increased lactic acid-acidosis can break down cell membran High intracellular Ca++ causes release of proteases Arachidonic acid leads to inflammation and free radicals Water influx causes cell edema Treatments Pharmacological blocking of NMDA receptors-tricky Block IP3 pathway Mechanisms of Excitotoxicity Rehabilitation and Plasticity Intensity and timing of rehabilitation are important Prolonged inactivation of cortical areas leads to losses in adjacent areas Timing is essential Early rehabilitation important Rehabilitation too early counterproductive Type of therapy also important Task-specific practice Important in motor learning Constraint induced therapy Intervening too early may exacerbate damage: excitotoxicity Chronic damage: Constraint-induced therapy promotes recovery of function Enriched environments Timing of CIMT Important Plasticity in Somatosens ory Cortex Effects of Constrai nt- Induced Moveme nt Therapy Ocular Dominance Columns Columns grow more apparent with visual experience