Neuron activity in the amygdaloid complex was studied in baseline conditions and on exposure to electrical stimulation of the prefrontal cortex in intact rats and rats subjected to prolonged emotional/pain stress (PEPS) using rats of bred strains with high (HT) and low (LT) thresholds of nervous system arousability; levels of genome instability were also studied in amygdaloid complex cells using a protein marker for double-stranded DNA breaks, i.e., histone H2AX phosphorylated at serine 139 (γ-H2AX phospho Ser139). We report the first finding of a direct link between basal (baseline) spike activity in amygdaloid complex neurons and their genome instability level, along with a relationship between basolateral amygdala neuron responses to excitatory stimulation of the infralimbic cortex and the innate genetically determined level of nervous system arousability. PEPS enhanced the functional activity of the amygdaloid complex in HT rats in terms of the baseline neuron spike activity frequency, mean spike number, and latency in responses to cortical stimulation. LT rats in the same conditions showed more significant increases in baseline neuron activity frequency, accompanied by increases in immunoreactivity of cells to γ-H2AX phospho Ser139 and a significant reduction in the latency of the responses of amygdalar neurons to cortical stimulation with no change in the number of spikes in responses.
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References
Airapetyants, M. G. and Vein, A. M., Neuroses in Research and the Clinic, Nauka, Moscow (1982).
Aleksandrova, N. P., Shiryaeva, N. V., Kratin, Yu. G., and Lopatina, N. G., “Brain activation thresholds in rats selected for neuromuscular apparatus arousability,” Dokl. Akad. Nauk. SSSR, 259, 1233–1235 (1981).
Arruda-Carvalho, M. and Clem, R. L., “Prefrontal-amygdala fear networks come into focus,” Front. Syst. Neurosci., 9, 145 (2015).
Ayrapetov, M. K., Gursoy-Yuzugullu, O., Xu, C., et al., “DNA doublestrand breaks promote methylation of histone H3 on lysine 9 and transient formation of repressive chromatin,” Proc. Natl. Acad. Sci. USA, 111, No. 25, 9169–9174 (2014).
Bekhtereva, N. P., The Healthy and Sick Human Brain, AST, Moscow, Sova, St. Petersburg, VKT, Vladimir (2010).
Bloodgood, D. W., Sugam, J. A., Holmes, A., and Kash, T. L., “Fear extinction requires infralimbic cortex projections to the basolateral amygdala,” Transl. Psychiatry, 8, No. 1, Art. No. 60 (2018).
Cho, J. H., Deisseroth, K., and Bolshakov, V. Y., “Synaptic encoding of fear extinction in mPFC-amygdala circuits,” Neuron, 80, No. 6, 1491–1507 (2013).
Delli Pizzi, S., Chiacchiaretta, P., Mantini, D., et al., “Functional and neurochemical interactions within the amygdalamedial prefrontal cortex circuit and their relevance to emotional processing,” Brain Struct. Funct., 222, No. 3, 1267–1279 (2017).
Du, J., Johnson, L. M., Jacobsen, S. E., and Patel, D. J., “DNA methylation pathways and their crosstalk with histone methylation,” Nat. Rev. Mol. Cell. Biol., 16, No. 9, 519–532 (2015).
Dyuzhikova, N. A. and Daev, E. V., “The genome and stress reactions in animals and humans,” Ekol. Genetika, 16, No. 1, 4–26 (2018).
Dyuzhikova, N. A., Skomorokhova, E. B., and Vaido, A. I., “Epigenetic mechanisms of formation of poststress states,” Usp. Fiziol. Nauk., 45, No. 1, 47–74 (2015).
Flint, M. S., Baum, A., Chambers, W. H., and Jenkins, F. J., “Induction of DNA damage, alteration of DNA repair and transcriptional activation by stress hormones,” Psychoneuroendocrinology, 32, No. 5, 470–479 (2007).
Gong, F. and Miller, K. M., “Histone methylation and the DNA damage response,” Mutat. Res., 780, 37–47 (2019).
Hare, B. D., Thornton, T. M., Rincon, M., et al., “Two weeks of variable stress increases gamma-h2ax levels in the mouse bed nucleus of the stria terminalis,” Neuroscience, 373, 137–144 (2018).
Jalbrzikowski, M., Larsen, B., Hallquist, M. N., et al., “Development of white matter microstructure and intrinsic functional connectivity between the amygdala and ventromedial prefrontal cortex: associations with anxiety and depression,” Biol. Psychiatry, 82, No. 7, 511–521 (2017).
Kuo, L. J. and Yang, L. X., “Gamma-H2AX – a novel biomarker for DNA double-strand breaks,” In Vivo, 22, No. 3, 305–9 (2008).
Levina, A. S., Bondarenko, N. A., Shiryaeva, N. V., et al., “Inherited diving behavior in rats as an adaptive factor,” Ekol. Genetika (2020), in press.
Lopatina, N. G. and Ponomarenko, V. V., “Studies of the genetic basis of higher nervous activity,” in: The Physiology of Behavior. Neurobiology, Batuev, A. S. (ed.), Nauka, Leningrad (1987), pp. 9–59.
Lyubashina, O. A. and Nozdrachev, A. D., “NO-dependent mechanisms of amygdalocortical influences,” Dokl. Akad. Nauk., 421, No. 2, 282–285 (2008).
Lyubashina, O. A., Panteleev, S. S., and Nozdrachev, A. D., Amygdalofugal Modulation of the Autonomic Centers of the Brain, Nauka, St. Petersburg (2009).
Lyubashina, O. and Panteleev, S., “Effects of cervical vagus nerve stimulation on amygdala-evoked responses of the medial prefrontal cortex neurons in rat,” Neurosci. Res., 65, No. 1, 122–125 (2009).
Maroun, M., “Stress reverses plasticity in the pathway projecting from the ventromedial prefrontal cortex to the basolateral amygdala,” Eur. J. Neurosci., 24, No. 10, 2917–2922 (2006).
Mitra, R., Jadhav, S., McEwen, B. S., et al., “Stress duration modulates the spatiotemporal patterns of spine formation in the basolateral amygdala,” Proc. Natl. Acad. Sci. USA, 102, No. 26, 9371–9376 (2005).
Ordyan, N. E., Vaido, A. I., Rakitskaya, V. V., et al., “Functioning of the hypophyseal-adrenocortical system in rats selected for electric current sensitivity thresholds,” Byull. Eksperim. Biol. Med., 125, No. 4, 443–445 (1998).
Panteleev, S. S., Bagaev, V. A., and Nozdrachev, A. D., Cortical Modulation of Visceral Reflexes, St. Petersburg University Press, St. Petersburg (2004).
Pavlova, M. B., “Epigenetic changes in the amygdala in rats with different nervous system arousability in response to emotional-pain stress,” Zdor. Osn. Chel. Potents. Probl. Puti Resh., 14, No. 2, 713–723 (2019).
Paxinos, G., and Watson, C., The Rat Brain in Stereotaxic Coordinates, Academic Press, (2007), 6th ed.
Peters, J., Kalivas, P. W., and Quirk, G. J., “Extinction circuits for fear and addiction overlap in prefrontal cortex,” Learn. Mem., 16, No. 5, 279–288 (2009).
Phan, K. L., Fitzgerald, D. A., Nathan, P. J., and Tancer, M. E., “Association between amygdala hyperactivity to harsh faces and severity of social anxiety in generalized social phobia,” Biol. Psychiatry, 59, No. 5, 424–9 (2006).
Quirk, G. J. and Mueller, D., “Neural mechanisms of extinction learning and retrieval,” Neuropsychopharmacology, 33, No. 1, 56–72 (2008).
Reznikov, R., Bambico, F. R., Diwan, M., et al., “Prefrontal cortex deep brain stimulation improves fear and anxiety-like behavior and reduces basolateral amygdala activity in a preclinical model of posttraumatic stress disorder,” Neuropsychopharmacology, 43, No. 5, 1099–1106 (2018).
Roozendaal, B., McEwen, B. S., and Chattarji, S., “Stress, memory and the amygdala,” Nat. Rev. Neurosci., 10, No. 6, 423–433 (2009).
Sierra-Mercado, D., Padilla-Coreano, N., and Quirk, G. J., “Dissociable roles of prelimbic and infralimbic cortices, ventral hippocampus, and basolateral amygdala in the expression and extinction of conditioned fear,” Neuropsychopharmacology, 36, No. 2, 529–538 (2011).
Stein, M. B., Goldin, P. R., Sareen, J., et al., “Increased amygdala activation to angry and contemptuous faces in generalized social phobia,” Arch. Gen. Psychiatry, 59, No. 11, 1027–1034 (2002).
Suberbielle, E., Sanchez, P. E., Kravitz, A. V., et al., “Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-β,” Nat. Neurosci., 16, No. 5, 613–621 (2013).
Vaido, A. I., Enin, L. D., and Shiryaeva, N. V., “Action potential conduction velocity in the tail and tibial nerves in rat strains selected for the excitability of the neuromuscular apparatus,” Genetika, XXI, No. 2, 262–264 (1985).
Vaido, A. I., Shiryaeva, N. V., Khichenko, V. I., et al., “Development of long-term post-tetanic potentiation and changes in S-100 protein content in hippocampal sections from rats with different functional states of the nervous system,” Byull. Eksperim. Biol. Med., 113, No. 6, 645–648 (1992).
Vaido, A. I., Shiryaeva, N. V., Pavlova, M. B., et al., “Selected rats grains with high and low arousability thresholds: a model for studies of maladaptive states depending on the nervous system arousability levels,” Lab. Zhivotn. Nauchn Issled., 3, 12–22 (2018).
Vyas, A., Jadhav, S., and Chattarji, S., “Prolonged behavioral stress enhances synaptic connectivity in the basolateral amygdala,” Neuroscience, 143, No. 2, 387–393 (2006).
Walker, D. L., Toufexis, D. J., and Davis, M., “Role of the bed nucleus of the stria terminalis versus the amygdala in fear, stress, and anxiety,” Eur. J. Pharmacol., 463, No. 1–3, 199–216 (2003).
Wang, J. and Lindahl, T., “Maintenance of genome stability,” Genomics Proteomics Bioinformatics, 14, No. 3, 119–121 (2016).
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Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 70, No. 5, pp. 655–667, September–October, 2020.
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Sivachenko, I.B., Pavlova, M.B., Vaido, A.I. et al. Spike Activity and Genome Instability in Neurons of the Amygdaloid Complex in Rats of Selected Strains with Contrasting Nervous System Arousability in Normal Conditions and Stress. Neurosci Behav Physi 51, 620–628 (2021). https://doi.org/10.1007/s11055-021-01115-0
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DOI: https://doi.org/10.1007/s11055-021-01115-0