NTNU, May 2009 ntnu.no/cb m 1 LEARNING AND MEMORY - Cellular and molecular mechanisms Øyvind Høydal NTNU, May 2009 ntnu.no/cb m 2 What is learning and memory? Learning can be defined as acquisition of new knowledge or skills and/or changes in behaviour as a result of experience. Memory refers to the storage and retrieval of learned knowledge, skills or behaviours. NTNU, May 2009 ntnu.no/cb m 3 NTNU, May 2009 ntnu.no/cb m 4 Information and skills are stored within the networks of neurons in the brain. When we learn, changes take place that alters the way neurons communicate with eachother. Can you guess what changes take place? NTNU, May 2009 ntnu.no/cb m 5 Cellular plasticity in learning and memory The efficacy of signalling between neurons are altered. New synapses form New neurons? NTNU, May 2009 ntnu.no/cb m 6 Aplysia californica as a model system for cellular learning and memory Studying cellular mechanisms for learning and memory in the mammalian brain is a formidable challenge due to the enormous number of neurons and the complexity of synaptic connections. Aplysia californica is an advantagous model organism because: - Neurons are quite few (20 000) and can be identified in the circuit. - Neurons are rather big, making them readily accessable for in vivo intracellular recordings NTNU, May 2009 ntnu.no/cb m 7 The gill-siphon reflex in aplysia offers a great opportunity to link changes in neurons and synapses with a behavioral output. When a mechanical stimulus is applied to the siphon, the slug responds by withdrawing its gill. NTNU, May 2009 ntnu.no/cb m 8 Gill-siphon-withdrawal reflex S M Tactile NTNU, May 2009 ntnu.no/cb m 9 The synapse and some common forms of short- term synaptic plasticity Synaptic facilitation: rapid increase in synaptic strength when two APs arrive at the axon terminal within a short interval of time. Increased Ca+ -influx causes more transmitter substance to be released. Synaptic depression: neurotransmitter release decline with sustained stimulation. A possible mechanism might be depletion of neurotransmitter-containing vesicles in the presynaptic neuron. Augementation (acts over seconds) and potentation (post-tetanic, acts over minutes) are other forms of short-term plasticity that enhance transmitter release due to prolonged and increased Ca+ levels. NMDA AMPA AMPA Na+ AP Ca+ Ca+ Ca + Na+ Na+ NTNU, May 2009 ntnu.no/cb m 10 Habituation in Aplysia Habituation: reduced response to a stimulus that is neither harmful nor beneficial. In Aplysia: if the siphon is touched repeatedly, the snail will eventually stop withdrawing its gill. The response in the sensory neuron is mostly unchanged, so the habituating effect on behaviour is likely to be mediated by a.