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Michael Ehlers"Shaping Neurons and Tuning Synapses in Dynamic Circuits"

Abstract :


The development and modification of neural circuits requires initial patterning of neuronal form.
We have explored signaling mechanisms underlying the specification of a single axon in pyramidal neurons in the developing mammalian forebrain. We have uncovered a signaling pathway activated by a secreted morphogen that directs neuronal polarity by controlling Par6 activity during axon generation. These results define a long-elusive extrinsic cue for neuronal polarity in vivo that patterns neural circuits in the developing brain. Following the establishment of initial connectivity, information storage and adaptation relies on variation in the form, magnitude, and propensity for plasticity at glutamatergic synapses. Optimal function of neuronal networks requires interplay between rapid forms of Hebbian plasticity and homeostatic mechanisms that adjust the threshold for plasticity, termed metaplasticity. Numerous forms of rapid synapse plasticity have been examined in detail. However, the rules that govern synaptic metaplasticity are much less clear. Here we demonstrate a local subunit-specific switch in NMDA receptors that alternately primes or prevents potentiation at single synapses. Together these findings define novel mechanisms for constructing and modifying complex neural circuitry.

Selected publications

Endocytic trafficking and recycling maintain a pool of mobile surface AMPA receptors required for synaptic potentiation. Petrini EM, Lu J, Cognet L, Lounis B, Ehlers MD, Choquet D. Neuron. 2009 Jul 16;63(1):92-105.
Molecular genetics and imaging technologies for circuit-based neuroanatomy. Arenkiel BR, Ehlers MD. Nature. 2009 Oct 15;461(7266):900-7

Daniel Choquet