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Altered glutamate/GABA equilibrium in aged mice cortex influences cortical plasticity

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Abstract

Age-related molecular changes in the synapse can cause plasticity decline. We found an impairment of experience-dependent cortical plasticity is induced by short lasting sensory conditioning in aged mice. However, extending the training procedure from 3 to 7 days triggered plasticity in the aged cortex of the same range as in young mice. Additionally, GABAergic markers (GABA, GAD67, VGAT) in young and aged groups that showed the plastic changes were upregulated. This effect was absent in the aged group with impaired plasticity, while the expression of Vglut1 increased in all trained groups. This may reflect the inefficiency of inhibitory mechanisms in the aging brain used to control increased excitation after training and to shape proper signal to noise ratio, which is essential for appropriate stimuli processing. HPLC analysis showed that the glutamate/GABA ratio was significantly reduced in aged animals due to a significant decrease in glutamate level. We also observed a decreased expression of several presynaptic markers involved in excitatory (vesicular glutamate transporter-vglut2) and inhibitory (glutamic acid decarboxylase-GAD67, vesicular GABA transporter VGAT) transmission in the aged barrel cortex. These changes may weaken the plasticity potential of neurons and impede the experience-dependent reorganization of cortical connections. We suggest that the imbalance toward inhibition resulting from a decrease of glutamate content in the aging cerebral cortex, together with GABAergic system ineffectiveness in upregulating GABA level after sensory training, contributes to the impairment of learning-dependent cortical plasticity.

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Acknowledgments

This work was supported by statutable funds of Nencki Institute of Experimental Biology and by Ministry of Science and Education Grant No: NN301248639.

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The authors declare no competing financial interests.

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Authors and Affiliations

  1. Laboratory of Neuroplasticity, Nencki Institute of Experimental Biology, 3 Pasteur St, 02-093, Warsaw, Poland

    Monika Liguz-Lecznar, Aleksandra Kaliszewska, Renata Zakrzewska & Malgorzata Kossut

  2. Institute of Psychiatry and Neurology, 8 Sobieskiego St, 02-957, Warsaw, Poland

    Malgorzata Lehner & Alicja Sobolewska

  3. Warsaw School of Social Sciences and Humanities, Chodakowska St., 19/31, 03-815, Warsaw, Poland

    Malgorzata Kossut

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  1. Monika Liguz-Lecznar
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  2. Malgorzata Lehner
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  3. Aleksandra Kaliszewska
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  4. Renata Zakrzewska
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  6. Malgorzata Kossut
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Correspondence to Monika Liguz-Lecznar.

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Liguz-Lecznar, M., Lehner, M., Kaliszewska, A. et al. Altered glutamate/GABA equilibrium in aged mice cortex influences cortical plasticity. Brain Struct Funct 220, 1681–1693 (2015). https://doi.org/10.1007/s00429-014-0752-6

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