Arc, also known as activity-regulated cytoskeleton-associated protein or Arg3.1, is an effector immediate-early gene [1-7, 9, 10]. It is critical for long-term memory consolidation and serves as a direct readout for neural activation during learning [2]. Arc contributes to diverse forms of synaptic plasticity, such as long-term potentiation, long-term depression, and synaptic scaling, mainly by regulating the trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors [2,3,5,7,8]. Given its crucial role in memory-related processes, genetic models are valuable tools for studying Arc [1, 2, 5-7, 10].

General Arc knockout rodent models develop a susceptibility to epileptic seizures, indicating that Arc, by modulating the excitatory-inhibitory balance in a neuronal network, is related to the pathogenesis of epilepsy [6]. Since Arc is essential for long-lasting information storage in the mammalian brain, its disruption likely affects normal cognitive aging processes [1,4]. Additionally, as Arc protein can self-assemble into retrovirus-like capsids and transfer genetic information between neurons, its absence may disrupt this inter-cellular communication mechanism important for synaptic plasticity [3,5,6,7].

In conclusion, Arc plays essential roles in memory consolidation, synaptic plasticity, and inter-cellular communication in neurons. The study of Arc knockout rodent models has provided insights into its role in epilepsy and potentially cognitive aging, highlighting its significance in understanding normal brain function and associated disease conditions.

References:

1. Myrum, Craig, Moreno-Castilla, Perla, Rapp, Peter R. 2022. 'Arc'-hitecture of normal cognitive aging. In Ageing research reviews, 80, 101678. doi:10.1016/j.arr.2022.101678. https://pubmed.ncbi.nlm.nih.gov/35781092/

2. Mabb, Angela M, Ehlers, Michael D. 2017. Arc ubiquitination in synaptic plasticity. In Seminars in cell & developmental biology, 77, 10-16. doi:10.1016/j.semcdb.2017.09.009. https://pubmed.ncbi.nlm.nih.gov/28890418/

3. Kedrov, Alexander V, Durymanov, Mikhail, Anokhin, Konstantin V. 2019. The Arc gene: Retroviral heritage in cognitive functions. In Neuroscience and biobehavioral reviews, 99, 275-281. doi:10.1016/j.neubiorev.2019.02.006. https://pubmed.ncbi.nlm.nih.gov/30772431/

4. Shepherd, Jason D. 2017. Arc - An endogenous neuronal retrovirus? In Seminars in cell & developmental biology, 77, 73-78. doi:10.1016/j.semcdb.2017.09.029. https://pubmed.ncbi.nlm.nih.gov/28941877/

5. Eriksen, Maria Steene, Bramham, Clive R. 2022. Molecular physiology of Arc/Arg3.1: The oligomeric state hypothesis of synaptic plasticity. In Acta physiologica (Oxford, England), 236, e13886. doi:10.1111/apha.13886. https://pubmed.ncbi.nlm.nih.gov/36073248/

6. Sibarov, Dmitry A, Tsytsarev, Vassiliy, Volnova, Anna, Savage, Elton D, Inyushin, Mikhail. 2023. Arc protein, a remnant of ancient retrovirus, forms virus-like particles, which are abundantly generated by neurons during epileptic seizures, and affects epileptic susceptibility in rodent models. In Frontiers in neurology, 14, 1201104. doi:10.3389/fneur.2023.1201104. https://pubmed.ncbi.nlm.nih.gov/37483450/

7. Hedde, Per Niklas, Malacrida, Leonel, Barylko, Barbara, Albanesi, Joseph P, Jameson, David M. 2021. Membrane Remodeling by Arc/Arg3.1. In Frontiers in molecular biosciences, 8, 630625. doi:10.3389/fmolb.2021.630625. https://pubmed.ncbi.nlm.nih.gov/33763452/

8. Korb, Erica, Finkbeiner, Steven. 2011. Arc in synaptic plasticity: from gene to behavior. In Trends in neurosciences, 34, 591-8. doi:10.1016/j.tins.2011.08.007. https://pubmed.ncbi.nlm.nih.gov/21963089/