Neuronal Plasticity, Learning and Memory. David Keays Institute of Molecular Pathology

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1 Neuronal Plasticity, Learning and Memory David Keays Institute of Molecular Pathology

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5 Structure 1. What is learning and memory? 2. Anatomical basis 3. Cellular basis 4. Molecular basis 5. Summary

6 Part I - Definition What is learning? The process by which we acquire knowledge about the world What is memory? The process by which that knowledge is encoded, stored, and later retreived Kandel et al, Principles of Neural Science

7 Part I Types of Memory Memory Short Term Memory Long Term Memory Declarative memory Procedural memory

8 Part I Types of Memory Memory Short Term Memory Long Term Memory Declarative memory e.g. Red bike Procedural memory e.g. Riding bike

9 Part I Why is it important?

10 Part I Why is it important?

11 Part I Why is it important?

12 Part I Why is it important? Memory is the glue that holds our mental life together. Without its unifying power, both our conscious and unconscious life would be broken into as many fragments as there are seconds in the day. Our life would be empty and meaningless Kandel et al, 2014

13 Part II Anatomical Basis

14 Part II Anatomical Basis

15 Part II Henry Molaison

16 Part II Henry Molaison William Scoville Medial temporal lobe resection Removed hippocampus and amygdala

17 Part II Henry Molaison William Scoville Medial temporal lobe resection Removed hippocampus and amygdala Annese et al, 2013

18 Part II Hippocampus It is concluded that the anterior hippocampus and hippocampal gyrus, either separately or together, are critically concerned in the retention of current experience

19 Part II Hippocampus

20 Part II Hippocampus

21 Part II Hippocampus Video courtesy of Richard Morris

22 Part II Hippocampus Morris et al, Nature 1982

23 Part II Hippocampus

24 Part II Hippocampus Pyramidal neurons Molecular layer CA1 CA3 Dentate Gyrus

25 Part II Hippocampus Fractured pyramidal cell layer. Defects in memory formation. Control Mutant Keays et al, Cell 2007 D E F

26 Part III Cellular Basis axon synaptic terminals soma dendrites - 85 billion neurons

27 Part III Cellular Basis axon synaptic terminals synapse - 85 billion neurons trillion synapses

28 Part III Cellular Basis One neuron, One memory

29 Part III Cellular Basis One neuron, One memory Network of neurons, One memory

30 Part III Cellular Basis

31 Part II Cellular Basis When an axon of cell A... excites cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one of both cells so that A s effeciency as one of the cells firing B is increased

32 Part III Cellular Basis Neurons that fire together, wire together

33 Part III Long Term Potentiation

34 Part III Long term potentiation Bliss and Lomo 1973

35 Part III Long term potentiation

36 Part III Long term potentiation Epsp excitatory post synaptic potential

37 Part III Long term potentiation

38 Part III Long term potentiation Epsp excitatory post synaptic potential

39 Part IV At the synapse

40 Part IV At the synapse AMPA Receptors Sodium permeable Phosphorylation influences localisation and conductance. KO animals have defects in LTP and memory formation.

41 Part IV At the synapse AMPA Receptors Sodium permeable Phosphorylation influences localisation and conductance. KO animals have defects in LTP and memory formation. NMDA Receptors Calcium permeable channel Magnesium block Antagonists (e.g. AP5) block LTP and memory formation Mg 2+

42 Part IV At the synapse

43 Part IV At the synapse

44 Part IV At the synapse

45 Part IV At the synapse CREB camp response element binding protein. Required for memory in flies, aplysia and mice. Transcription factor. Turns on proteins c-fos, Bdnf, fgf1. Important for the formation of new synaptic connections.

46 Part IV At the synapse

47 Part IV Dendritric spines Spines are membranous protrusions located along the dendrites of neurons.

48 Part IV Dendritric spines LTP

49 Part IV At the synapse

50 Part IV Molecules and Emotion

51 Part IV Molecules and Emotion Noradrenalin

52 Part IV Molecules and Emotion + Noradrenalin

53 Part IV Molecules and Emotion + Noradrenalin

54 Part IV Molecules and Emotion ADRENERGIC RECEPTOR

55 Part IV Molecules and Emotion ADRENERGIC RECEPTOR

56 Part IV Molecules and Emotion ADRENERGIC RECEPTOR Enhanced LTP

57 V - Summary Classifications of memory Declarative memory relies on the hippocampus LTP is believed to be the cellular correlate of memory LTP is mediated by glutamate, results in protein synthesis Memory formation is associated with remodelling of dendritic spines. Hormones can enhance LTP and memory formation

58 Summary keayslab.org/teaching Galizia et al, Neurosciences from Molecule to Behaviour. chpt 28 Kandel et al, Principles of Neuroscience, chpt 62-63

59 Part III Long Term Potentiation

60 Part III Long term potentiation

61 Part II Spines