Anna Moore, PhD

Postdoctoral Associate
Department of Biology
Brandeis University
(October 5, 2015)

Novel Molecular Mechanism, the Activity-Dependent Gene Rem2, Underlying Visual Circuit Plasticity

Experience during development plays a major role in the formation of neuronal circuits. But levels of different proteins can also have a large effect on how the circuit develops. Activity in neurons can cause levels of different proteins to change, and can affect the formation of the circuit. In her talk, for example, Dr. Moore discussed her work with the molecule Rem2, without which a developing circuit of neurons in visual cortex cannot adapt to new circumstances. Without flexibility, a circuit cannot adapt to new sensory input and cannot function normally in an ever-changing environment.

The construction and adaptation of neuronal circuits is a carefully orchestrated series of events, which includes the formation of synapses and the morphogenesis of the dendritic arbor of individual neurons. These events are largely dependent on the relationship between spontaneous and experience-dependent activity and underlying intracellular signaling pathways. While changes in neuronal structure and function can occur on many levels, the identity of the molecules that link these changes in sensory experience to corresponding changes in intracellular signaling remains largely unknown. We have identified a previously obscure Ras-like GTPase, Rem2 that has several hallmarks of being a major activity-dependent plasticity gene. For example, dialing Rem2 expression up or down in the context of neuronal activity positively regulates synapse formation while negatively regulating dendritic complexity. Further, Rem2 is a novel target of CaMKII, whereas phosphorylation of Rem2 by CaMKII regulates Rem2 subcellular localization and function.

In this talk, I focused on the novel role of Rem2 as an activity-regulated molecule required for neuronal plasticity in the visual system. In response to visual experience, hanges in neural activity results in an upregulation of Rem2 expression in the visual cortex. In turn, Rem2 functions to set the intrinsic excitability of the neuron and promote synaptic scaling in response to occlusion of vision in one eye. As a result, in the absence of Rem2, mice are unable to exhibit ocular dominance plasticity, or the ability to shift the responsiveness from the closed eye to the open eye. Thus, Rem2 plays an important role in maintaining the nervous system’s ability to adapt its neuronal network in response to changes in sensory input.