Richard Huganir, The Johns Hopkins University, Baltimore, USA
Julie Kauer, Brown University, Providence, USA
Dominique Muller, University of Geneva, Switzerland
Pico Caroni, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
Lu Chen, Stanford University, USA
Pierre-Marie Lledo, Institut Pasteur, Paris, France
Robert Malenka and Julie Kauer
Overview of major forms of synaptic plasticity
We will introduce the history of the study of NMDA receptor-dependent LTP and LTD and what is generally accepted about their basic mechanisms. This will include a discussion of modern approaches to understanding the mechanisms and functions of synaptic plasticity. We will then discuss other prominent forms of long-term synaptic plasticity including the endocannabinoid-mediated LTD found at multiple excitatory and inhibitory synapses throughout the CNS. Unusual forms of LTP and LTD will be presented including two examples of LTP found at inhibitory CNS synapses.
Postsynaptic molecular architecture and plasticity: Neurotransmitter receptor structure and function and regulation of receptor function and membrane trafficking.
A great deal is known about the molecular architecture of the postsynaptic density of excitatory synapses and the structure of its glutamate receptors. In these lectures, I will review the key postsynaptic proteins found in the postsynaptic density and then focus on neurotransmitter receptor structure and function in the context of receptor trafficking during long-term synaptic and experience-dependent plasticity.
Synaptic cell adhesion and its role in synapse specification
These lectures will introduce the topic of synaptic cell adhesion and its importance focusing initially on neuroligins and neurexins, their structures and putative functions. Other important synaptic cell adhesion proteins will be introduced including LRRTMs, SynCams and perhaps cadherins. Their involvement in disease will be discussed as well as their contribution to the specificity of synapse formation, synapse maintenance and the detailed functional properties of synapses.
Structural plasticity of spines and synapses
The concept of Hebbian plasticity based on changes in synaptic strength is central to our understanding of the mechanisms of learning and memory. However, accumulating evidence indicates that plasticity also includes a structural remodelling of synaptic networks and connectivity through mechanisms of synapse formation, stabilization and elimination. These synaptic rearrangements occur in a spatially organized manner, they are regulated by neuronal activity and involve signaling pathways that overlap with those of Hebbian plasticity. These structural rearrangements are believed to be important during development by providing specificity in the wiring of synaptic networks and evidence suggests that alteration of these mechanisms could contribute to the pathogenesis of several developmental psychiatric disorders such as intellectual disability, autism spectrum disorders and schizophrenia.
Structural plasticity of circuits
These lectures will begin to provide an integration of all of the previous lectures by demonstrating how changes in activity levels result in the restructuring of entire circuits. Examples from a variety of different preparations including invertebrate species and humans will be provided.
Adult-born neurons in olfactory bulb circuits: A hub that links brain states to sensory experience.
These lectures will provide an introduction to the topic of neurogenesis focusing on the production of new neurons in the olfactory bulb throughout life as a crucial mechanism underlying learning-induced circuit remodeling. This recruitment of new neurons depends not only on sensory exposure but also on the context in which the stimulus is perceived. We already know that both integration and survival of adult-born neurons depend on learning and that activation of adult-born neurons, in turn, specifically improves olfactory learning and long-term memory. In this course, the nature of the circuit and the synaptic mechanisms underlying this reciprocity will be discussed.
Molecular mechanisms and functional impact of homeostatic synaptic plasticity.
A long-standing question in the field of neuroscience is how plastic changes at synapses in a circuit enable learning, encode memory, and drive behavior. Compared to the progress made in relating Hebbian plasticity to animal learning, much less is known about the behavioral significance of homeostatic synaptic plasticity. I will first review recent progress in our understanding of the molecular signaling pathways underlying homeostatic synaptic plasticity at both excitatory and inhibitory synapses. I will then discuss the impact of homeostatic adjustment of excitatory and inhibitory synaptic strength on synaptic excitation/inhibition balance, and how such shift in E/I ratio may act as a form of metaplasticity to modify Hebbian plasticity rules and influence learning of the organism. A short review on the link between homeostatic synaptic plasticity and neurological diseases will be provided as well.