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

Neuronal Plasticity, Learning and Memory David Keays Institute of Molecular Pathology http://keayslab.org

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

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

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

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

Part I Why is it important?

Part I Why is it important?

Part I Why is it important?

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

Part II Anatomical Basis

Part II Anatomical Basis

Part II Henry Molaison

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

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

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

Part II Hippocampus

Part II Hippocampus

Part II Hippocampus Video courtesy of Richard Morris

Part II Hippocampus Morris et al, Nature 1982

Part II Hippocampus

Part II Hippocampus Pyramidal neurons Molecular layer CA1 CA3 Dentate Gyrus

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

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

Part III Cellular Basis axon synaptic terminals synapse - 85 billion neurons - 100 trillion synapses

Part III Cellular Basis One neuron, One memory

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

Part III Cellular Basis

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

Part III Cellular Basis Neurons that fire together, wire together

Part III Long Term Potentiation

Part III Long term potentiation Bliss and Lomo 1973

Part III Long term potentiation

Part III Long term potentiation Epsp excitatory post synaptic potential

Part III Long term potentiation

Part III Long term potentiation Epsp excitatory post synaptic potential

Part IV At the synapse

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

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+

Part IV At the synapse

Part IV At the synapse

Part IV At the synapse

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.

Part IV At the synapse

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

Part IV Dendritric spines LTP

Part IV At the synapse

Part IV Molecules and Emotion

Part IV Molecules and Emotion Noradrenalin

Part IV Molecules and Emotion + Noradrenalin

Part IV Molecules and Emotion + Noradrenalin

Part IV Molecules and Emotion ADRENERGIC RECEPTOR

Part IV Molecules and Emotion ADRENERGIC RECEPTOR

Part IV Molecules and Emotion ADRENERGIC RECEPTOR Enhanced LTP

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

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

Part III Long Term Potentiation

Part III Long term potentiation

Part II Spines