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Knowledge Objectives:

Neuroplasticity. Knowledge Objectives:. What is “ Brain Plasticity ” What is experience-dependent plasticity and what are some of its different forms. What is LTP and LTD, and what is their relationship to learning and memory.

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Knowledge Objectives:

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  1. Neuroplasticity Knowledge Objectives: What is “Brain Plasticity” What is experience-dependent plasticity and what are some of its different forms. What is LTP and LTD, and what is their relationship to learning and memory. What are AMPA and NMDA receptors, and what are their roles in synaptic transmission. What are dendritic spines. What is the post-synaptic density. Be able to explain the effects of visual experience on calibration of the auditory and visual maps in the barn owl. What are the effects of forced motor use or environmental enrichment on plasticity. Is there a relationship between neurogenesis in the adult brain and plasticity. Be able to discuss changes in cortical representation in use/disuse of limbs and digits.

  2. 1) What do we mean by Brain Plasticity. Brain plasticity refers to the brains ability to change structure and function. Experience is a major stimulant of brain plasticity 2) The Good, the Bad, and the Ugly of plasticity

  3. Hebbian Plasticity Ramon Cajal (1894): “mental exercise facilitates a greater development of the protoplasmic apparatus and of the nervous collaterals in the part of the brain in use” Donald Hebb (1949): “When an axon of cell A is near enough to excite cell B repeatedly, or consistently takes place in firing it, some growth or metabolic changes takes place in one or both cells such that A’s efficiency, as one of the cells firing B, is increased.” In short, Hebb’s postulate states that coincident activity in two, synaptically coupled neurons would cause increases in the synaptic strength between them. In short-short, “neurons that fire together, wire together”

  4. Cartoon of Hebbian processes weakened/eliminated pre post weak Input 1 strong Input 2 strengthened Mechanism of change in synapse efficiency may be presynaptic (increased neurotransmitter release) or postsynaptic (change in response), or both.

  5. Experience-Dependent Plasticity Examples 1) Learning and Memory 2) Adaptive modifications of neuronal circuits during critical periods of development 3) Adaptations underlying drug addiction 4) Recovery of function after injury 5) Neurogenesis in the adult brain

  6. The hippocampus is a brain region essential for formation of new memories, especially memories of objects and space (spatial memory) Electrophysiological recording from the CA1 region of the hippocampus

  7. Phenomenon of Long-Term potentiation (LTP) -Occurs at a variety of neural synapses -Can be explained by Hebbian mechanisms -Can be divided into temporal components -Counterpart is long-term depression (LTD) -”Classical forms” of LTP (and LTD) are dependent upon activation of NMDA receptors and calcium influx. -Calcium exerts bidirectional control and acts locally (input specific LTP) -Can be observed both in vitro and in vivo (where it can last for days/weeks) -Hippocampal LTP is thought to be a cellular model of learning and memory

  8. Effects of conditioning stimulation delivered to the Schaffer collaterals at different frequencies. Evidence for a sliding modification threshold. Frequency-response functions derived from visual cortex of light-deprived (solid symbols) and normal (open symbols) rats.

  9. Dendritic Spines -Usually receives a single excitatory glutamatergic synapse -Are the smallest functional compartments of the neuron -Are multifunctional microintegrative units that integrate a range of functions -Play a critical role in structural plasticity

  10. Role of surface expression of AMPA receptors during LTP/LTD AMPA receptors are rapidly cycled in and out of the PSD Decreased AMPA receptor surface expression results in decreased postsynaptic response Increased AMPA receptor surface expression results in enhanced postsynaptic response

  11. Increased spine density as a structural bases of late-LTP

  12. Sound localization calibrated by early visual experience in the barn owl

  13. Sound localization calibrated by early visual experience in the barn owl Ascending auditory pathway in the optic tectum of the barn owl. Inputs that enter the optic tectum that already contain information about ITD. The ICC is organized topographically by frequency. In the ICC, ITD information is combined to synthesize a map of auditory space in the ICX. From the ICX the auditory map is conveyed to the optic tectum. Here the auditory map is merged and aligned with the visual map of space to produce a multimodal space map. ICC = central nucleus of the inferior colliculus ICX = external nucleus of the inferior colliculus ITD = Interaural time difference

  14. Rearing owls with laterally displacing optical prisms causes an adaptive shift in the tuning of neurons in the optic tectum for ITD

  15. Prism experience induces a shift in pattern of axonal projects from the ICC to the ICX. This is thought to underlie the calibration of the auditory and visual fields, and may to be mediated by NMDA receptors (e.g awakening of silent-synapses). Visual calibration occurs only during a critical period prior to sexual maturity. Removal of prisms from adult animal results in rapid shift of the ITD back to normal.

  16. The ability of drugs of abuse to co-opt plastic processes of the brain may contribute to addiction and drug seeking behavior Amphetamine treatment of rats produced persistent structural modifications of the dendritic tree. These changes, which include increases in dendritic length, spine number and branched spines, occur only in brain regions implicated in addiction. nucleus accumbens prefrontal cortex

  17. --Hebb’s: “Neurons that fire together, wire together” Hebbian plasticity + cocaine --Willie Nelson “If your wired, your fired”

  18. Motor activity following brain injury can prevent loss of function Recent studies have shown that implementation of forced motor use of affected limbs after stroke improves functional outcome. In the study below, forced limb-use was found to prevent behavioral deficits associated with 6-hydroxydopamine infusion (a model of Parkinson.s disease) Limb-use asymmetry was prevented with early forced use, but not in animals in a delayed forced-use condition, which showed behavior similar to that of non-cast animals. Animals that received the cast on days 3-9 also showed no significant group difference from shams.

  19. An enriched environment promotes experience-induced plasticity

  20. Historical View of Neurogenesis in the Adult Brain

  21. An enriched environment stimulates neurogenesis in the adult hippocampus Enriched environments also enhance performance in learning and memory task. Is there an association with enhance neurogenesis? Confocal microscopic analysis of immunofluorescent triple-labeling of BrdU-positive cells (red) 1 d (A) and 4 weeks (B-D) after the last injection of BrdU. A, Overview of the distribution of BrdU-positive cells along the border between the arrowhead-shaped granule cell layer of the dentate gyrus and the hilar area CA4 (compare with hatched columns in Fig. 3A). In addition there are some proliferating cells in the hilus itself and in the molecular layer. No qualitative difference among the four groups could be found. Four weeks after injection the phenotypes of BrdU-labeled cells were examined (B-D). Markers were NeuN (green) for neurons and S100 (blue) for astrocytes. B, Two BrdU-labeled neurons (orange = red + green) and one BrdU-positive cell that is neither NeuN- nor S100-positive in an Enr-6 animal. C, BrdU-labeled neuron with the typical chromatin pattern of a granule cell in an Enr-18 animal. D, One BrdU-labeled astrocyte (pink = red + blue, left) and one BrdU-labeled neuron (orange, right). Scale bar (in A): A, 200 µm; B, C, 12 µm; D, 20 µm.

  22. Learning enhances adult neurogenesis in the hippocampus The number of new neurons in the granule cell layer (Gcl) of adult rats increases following spatial learning in the Morris water maze. Confocal laser scanning microscopic images of BrdU labeled cells (arrows) reveal a difference in number between control (a) and spatial learning (b) adult rats No increases in BrdU labeled cells was observed following non-hippocampal dependent learning task. Thus, learning appears to have a trophic effect on adult generated hippocampal neurons

  23. New cells differentiate into functional mature neurons that are integrated into the hippocampal circuitry and are plastic

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