title: Altered glutamate/GABA equilibrium in aged mice cortex influences cortical plasticity.
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.
authors.forename: Monika
authors.initials: M
authors.lastname: Liguz-Lecznar
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Lehner
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Kaliszewska
authors.forename: Renata
authors.initials: R
authors.lastname: Zakrzewska
authors.forename: Alicja
authors.initials: A
authors.lastname: Sobolewska
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kossut
mesh_terms: D000375:Aging; D000818:Animals; D003214:Conditioning, Classical / Q000502:physiology; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D018698:Glutamic Acid / Q000032:analysis*; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity; D017729:Presynaptic Terminals / Q000378:metabolism; D013003:Somatosensory Cortex / Q000737:chemistry / Q000378:metabolism*; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000032:analysis*
chemical_list: C493477:Slc17a6 protein, mouse; D050599:Vesicular Glutamate Transport Protein 2; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1