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Authors & Affiliations
Daniela Carolina Ballesteros Cadena, Alexa-Nicole Sliby, Ute Süsens, Dietmar Kuhl, Ora Ohana
Abstract
The activity-regulated gene Arc/Arg3.1 is known for its vital role in memory consolidation and synaptic plasticity [1]. Our recent research revealed a novel role for Arc/Arg3.1 in developing brain circuits. In the hippocampus, a spontaneous wave of Arc/Arg3.1 upregulation is observed during the first postnatal month, crucial for establishing proper spatial learning and intact hippocampal oscillations in adult mice [2]. Since the emergence of hippocampal oscillatory rhythms relies on an intricate interplay between excitatory and inhibitory synaptic connections, we hypothesized that early postnatal Arc/Arg3.1 expression modifies the architecture and properties of these connections. To test this hypothesis, we investigated synaptic transmission in the hippocampus of adult WT and KO mice, where Arc/Arg3.1 was genetically deleted during development. We recorded ex-vivo, field potentials and synaptic currents from CA1, and performed quantitative confocal and electron microscopy and protein biochemistry. We find alterations in the numbers, kinetics, and structure of hippocampal synapses in the KO and cKO mice. These alterations are influenced by the availability of Arc/Arg3.1 during early postnatal development but persist into adulthood. We anticipate that alterations of specific synaptic properties contribute to dysfunctional network oscillations and impaired learning.[1] Plath, Niels, et al. "Arc/Arg3. 1 is essential for the consolidation of synaptic plasticity and memories." Neuron 52.3 (2006): 437-444.[2] Gao, Xiaoyan, et al. "Arc/Arg3. 1 mediates a critical period for spatial learning and hippocampal networks." Proceedings of the National Academy of Sciences 115.49 (2018): 12531-12536.