Subtype-specific roles for presynaptic NMDA receptors in experience-dependent plasticity and visual cortical development

Larsen, Rylan Scott

Subtype-specific roles for presynaptic NMDA receptors in experience-dependent plasticity and visual cortical development Public Deposited

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March 20, 2019

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Larsen, Rylan Scott
- Affiliation: School of Medicine, Department of Cell Biology and Physiology

Abstract

A defining property of the brain is its ability to modify neuronal circuits in response to sensory stimuli to allow for adaptive responses to the environment. In the visual cortex, sensory stimuli shape cortical circuitry through activity-dependent processes. These processes are diverse, however one such mechanism for sensory experience-induced changes in cortical function is Hebbian plasticity. NMDA-type glutamate receptors (NMDARs) are critical to many forms of Hebbian plasticity including LTP and LTD and therefore likely contribute significantly to the development of sensory cortices. NMDARs canonically are postsynaptic receptors, however recent evidence also demonstrates roles for presynaptic NMDARs in synaptic plasticity and modulating synaptic transmission. In L2/3 of the visual cortex, the molecular identity of presynaptic NMDARs had been explored, but previous findings did not explain how these receptors functioned in manners distinct from their postsynaptic counterparts. I found that the NMDAR subunit GluN3A (NR3A) was critical for the function of presynaptic NMDARs in the visual cortex. Subsequently, I observed that presynaptic NMDARs and GluN3A were regulated by visual experience. The reexpression of presynaptic NMDARs following visual experience resulted in restoration of the contribution of these receptors to spike timing-dependent plasticity and to glutamate release from L4 inputs. These findings suggest an important role for presynaptic, GluN3A-containing NMDARs in the function of the visual cortex and its modification by sensory experience.

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