This document discusses neuronal plasticity, which refers to the brain's ability to change and adapt as a result of experience. It describes various types and mechanisms of neuroplasticity, including enhancement of existing connections through synapse development and strengthening, and formation of new connections through unmasking of silent synapses and axon sprouting. It also discusses cortical remapping in deaf individuals and long-term potentiation as the basis of neuronal plasticity. Synaptic plasticity can be measured in the hippocampus, where strong stimulation leads to calcium influx and activation of protein kinases that strengthen synapses.

1. Neuronal PlasticityBySyedMujtabaHasnain Nadir Mubarak RazaWagha

2. What is neuronal plasticity?Plasticity is the quality of being ‘plastic’ or formative.Neuronal plasticity refers to the ability of the brain to change and adapt itself as a result of one’s experience.

3. Applications of Neuronal Plasticity‘Learning new things’‘Making new memories’‘Rewiring circuits’

4. Types of Long-term Memory

5. The NS is a series of connectionsBirth = 100 billion neurons6 year old has twice as many synapses as an adultBy late adolescence, synapses begin to disappearhttp://www.eng.yale.edu/synapses.htm

6. Types of NeuroplasticityTypeMechanismDuration1. Enhancement of existing connections Synapse development Physiological ms-1 to hours Synapse strengthening Biochemical hours to days2. Formation of new connections Unmasking Physiological minutes to days Sprouting Structural days to months3. Formation of new cells Self-replication stem cell variable

7. Enhancement of existing connectionsIncreased use of a synapse in existing pathways e.g. learning a new task Or alternative pathways following damageCortical re-mapping (phantom limb)

8. Synapse developmentIncreased afferent input+New synapses evolve leading to increased excitation++

9. Synapse strengtheningTwo point discrimination threshold in pianists index fingerRLRagert et al., 2004

10. Synaptic StrengtheningFacilitation (10-100 ms)Augmentation (several seconds)Potentiation (seconds to minutes)

11. Formation of new connectionsUnmasking of pre-existing pathwaysSprouting of new pathways

12. Unmasking of silent synapsesPossible reasons why some synapses could be ‘silent’On distal dendritesInhibited by dominant pathwaysToo little transmitterToo few receptorsDon’t fire with other inputs

13. Unmasking – inhibition of subservient pathway by dominant pathway Parallel pathway; neurons with a comparable roleSubservient pathwayDominant pathway++

14. UnmaskingLesion to dominant pathwaySubservient pathway is unmasked++Activity is continued despite lesion

15. SproutingCell bodyAPAxon

16. SproutingINJURYlesionNerve Growth Factor (NGF)

17. SproutingINJURYNeurite induced to sprout by NGFlesionNGF

18. SproutingInjury results in cell deathCell is re-innervated from alternative stimulusSprouting may be a means of recovery; it may also produce unwanted effects

19. NeurogenesisReplacing dying or damaged neural cells with new onesNew cells originate from stem cells Introduced stem cells are stimulated to produce neural cells by nerve growth factors (NGF)Stem cell/www.stanford.edu/group/hopes/rltdsci/nplast

20. Cortical Re-MappingPeople born deaf

21. Cortical Re-MappingPeople born deafWhat happens?

22. Cortical Re-MappingPeople born deafWhat happens?Visual areas increase in size and “jobs”Cortical Re-MappingPeople born deafWhat happens?Visual areas increase in size and “jobs”

23. Auditory areas may be “taken over” for visual function Cortical Re-MappingPeople born deafWhat happens?Visual areas increase in size and “jobs”

24. Auditory areas may be “taken over” for visual function

25. Improved attention to movement in the peripheryThe Basis of Neuronal Plasticity Hebb’s Rule :“Neurons that fire together, wire together.””Neurons that fire apart, wire apart.”

26. From The Organization of Behavior by Donald Hebb, 1949:"When one cell repeatedly assists in firing another, the axon of the first cell develops synaptic knobs (or enlarges them if they already exist) in contact with the soma of the second cell."Hebb postulated that this behavior of synapses in neuronal networks would permit the networks to store memories.

27. Synaptic StrengtheningFacilitation (10-100 ms)Augmentation (several seconds)Potentiation (seconds to minutes)

28. Long Term PotentiationIn neuroscience, long-term potentiation (LTP) is a long-lasting enhancement in signal transmission between two neurons that results from stimulating them synchronously.

29. Input specificityOnce induced, LTP at one synapse does not spread to other synapses; rather LTP is input specific.Cooperativity LTP can be induced by strong stimulation at one synapseOR Weak stimulation at multiple synapses which together depolarize the post synaptic membrane to induce LTP

30. Hippocampus Function: • Consolidation of New Memories • Emotions• Navigation• Spatial Orientation

31. Synaptic Plasticity Can Be Measured in Simple Hippocampal CircuitsThe post-synaptic region has both NMDA and AMPA receptors.Glutamate first activates AMPA receptors. NMDA receptors do not respond until enough AMPA receptors are stimulated and the neuron is partially depolarized.

32. Synaptic Plasticity Can Be Measured in Simple Hippocampal CircuitsNMDA receptors at rest have a magnesium ion (Mg2+) block on their calcium (Ca2+) channels.After partial depolarization, the block is removed and the NMDA receptor allows Ca2+ to enter in response to glutamate.

33. Figure 17.22 Roles of NMDA and AMPA Receptors in the Induction of LTP in CA1 Region (Part 1)

34. Figure 17.22 Roles of NMDA and AMPA Receptors in the Induction of LTP in CA1 Region (Part 2)

35. Figure 17.22 Roles of NMDA and AMPA Receptors in the Induction of LTP in CA1 Region (Part 3)

36. Synaptic Plasticity Can Be Measured in Simple Hippocampal CircuitsThe large Ca2+ influx activates certain protein kinases – enzymes that add phosphate groups to protein molecules.One protein kinase is CaMKII – it affects AMPA receptors in several ways:Causes more AMPA receptors to be produced and inserted in the postsynaptic membrane.

37. Synaptic Plasticity Can Be Measured in Simple Hippocampal CircuitsCaMKII :Moves existing nearby AMPA receptors into the active synapse.Increases conductance of Na+ and K+ ions in membrane-bound receptors.These effects all increase the synaptic sensitivity to glutamate.The activated protein kinases also trigger protein synthesis

38. Synaptic Plasticity Can Be Measured in Simple Hippocampal CircuitsStrong stimulation of a postsynaptic cell releases a retrograde messenger that travels across the synapse and alters function in the presynaptic neuron. More glutamate is released and the synapse is strengthened.

39. Synaptic Plasticity Can Be Measured in Simple Hippocampal CircuitsSomatic intervention experiments – pharmacological treatments that block LTP impair learning.Behavioral intervention experiments – show that training an animal in a memory task can induce LTP.

40. Can YOU see with your tongue?