Neuregulin and ErbB expression is regulated by development and sensory experience in mouse visual cortex

Abstract

Neuregulins (NRGs) are protein ligands that impact neural development and circuit function. NRGs signal through the ErbB receptor tyrosine kinase family. NRG1/ErbB4 signaling in parvalbumin-expressing (PV) inhibitory interneurons is critical for visual cortical plasticity. There are multiple types of NRGs and ErbBs that can potentially contribute to visual cortical plasticity at different developmental stages. Thus, it is important to understand the normal developmental expression profiles of NRGs and ErbBs in specific neuron types in the visual cortex, and to study whether and how their expression changes in PV inhibitory neurons and excitatory neurons track with sensory perturbation. Cell type-specific translating ribosome affinity purification and qPCR was used to compare mRNA expression of nrg1,2,3,4 and erbB1,2,3,4 in PV and excitatory neurons in mouse visual cortex. We show that the expression of nrg1 and nrg3 decreases in PV neurons at the critical period peak, postnatal day 28 (P28) after monocular deprivation and dark rearing, and in the adult cortex (at P104) after 2-week long dark exposure. In contrast, nrg1 expression by excitatory neurons is unchanged at P28 and P104 following sensory deprivation, whereas nrg3 expression by excitatory neurons shows changes depending on the age and the mode of sensory deprivation. ErbB4 expression in PV neurons remains consistently high and does not appear to change in response to sensory deprivation. These data provide new important details of cell type-specific NRG/ErbB expression in the visual cortex and support that NRG1/ErbB4 signaling is implicated in both critical period and adult visual cortical plasticity.

The critical period: neurochemical and synaptic mechanisms shared by the visual cortex and the brain stem respiratory system

“…Multiple intracellular and extracellular agents are involved in cortical plasticity during the critical period, such as the activation of tissue plasminogen activators, endocannabinoids, orthodenticle homeobox 2 (Otx2), neuregulin, extracellular signal-regulated kinase 1,2 (ERK1/2) and epigenetic factors, whereas plasticity is inhibited by such agents as perineuronal nets, myelin and Nogo receptors [4,5,30]. These agents have been well characterized in the murine visual cortex, but little studied in the rat visual cortex or the respiratory system.…”

Host interneurons mediate plasticity reactivated by embryonic inhibitory cell transplantation in mouse visual cortex

“…Exogenous NRG1 blocks the reduction in binocular PV interneuron responses. The expression of NRG1 in PV interneurons is developmentally regulated 11,15 . Its expression in the visual cortex starts high in early development, remains high during the juvenile critical period but decreases significantly in the adult cortex.…”

“…The resulting reduction in PV cell activity is necessary for the subsequent reorganization of the excitatory circuit 10,11 . The level of NRG1 within PV interneurons peaks during the early juvenile development but gradually decreases as the cortex matures 11,15 . These results suggest that NRG1/ErbB4 signaling may be involved in juvenile cortical plasticity.…”

Effect of regulation of the NRG1/ErbB4 signaling pathway on the visual cortex synaptic plasticity of amblyopic adult rats

“…It is affected by a family of epidermal growth factor domain‐containing receptor ligands that are expressed in the nervous system, and NRG1 is best characterized among these. [ 15 ] Several studies have shown that the NRG1/ErbB4 signaling pathway in PV inhibitory interneurons is critical for the activation of visual cortex plasticity. It controls the excitatory synaptic input to PV neurons so that PV‐cell‐mediated cortical disinhibition can occur after visual deprivation.…”