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Review
. 2017 Aug;16(4):634-643.
doi: 10.1111/acel.12605. Epub 2017 May 12.

The space where aging acts: focus on the GABAergic synapse

Aleksandra Rozycka  1 , Monika Liguz-Lecznar  1
Affiliations
Review

The space where aging acts: focus on the GABAergic synapse

Aleksandra Rozycka et al. Aging Cell. 2017 Aug.

Abstract

As it was established that aging is not associated with massive neuronal loss, as was believed in the mid-20th Century, scientific interest has addressed the influence of aging on particular neuronal subpopulations and their synaptic contacts, which constitute the substrate for neural plasticity. Inhibitory neurons represent the most complex and diverse group of neurons, showing distinct molecular and physiological characteristics and possessing a compelling ability to control the physiology of neural circuits. This review focuses on the aging of GABAergic neurons and synapses. Understanding how aging affects synapses of particular neuronal subpopulations may help explain the heterogeneity of aging-related effects. We reviewed the literature concerning the effects of aging on the numbers of GABAergic neurons and synapses as well as aging-related alterations in their presynaptic and postsynaptic components. Finally, we discussed the influence of those changes on the plasticity of the GABAergic system, highlighting our results concerning aging in mouse somatosensory cortex and linking them to plasticity impairments and brain disorders. We posit that aging-induced impairments of the GABAergic system lead to an inhibitory/excitatory imbalance, thereby decreasing neuron's ability to respond with plastic changes to environmental and cellular challenges, leaving the brain more vulnerable to cognitive decline and damage by synaptopathic diseases.

Keywords: GABA; GABAergic; ageing; aging; postsynaptic; presynaptic; synapse.

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Figures

Figure 1
Figure 1
Age‐related changes influence learning‐dependent plasticity in the mouse somatosensory cortex. From the bottom: Aging alters the level of several proteins related to glutamatergic and GABAergic neurotransmission in the somatosensory (SI) cortex of mice. mRNA for those proteins, with the exception of VGAT, is unaltered. Due to the decreased level of glutamate with an unchanged level of GABA in aged mouse SI, a lower glutamate‐to‐GABA ratio can be observed, suggesting an imbalance between excitation and inhibition. When submitted to short (3‐day) sensory training based on a classical conditioning paradigm (conditioned tactile stimulus paired with an unconditioned aversive stimulus), young mice elaborate functional cortical plasticity. This plastic change is visible, after mapping brain activity using the 2‐DG method, as an enlargement of the functional cortical representation of the trained row of vibrissae. Aged (1‐year‐old) mice do not demonstrate such plasticity after short training, even though they present the conditioned response similarly to the young mice. After longer (7‐day) conditioning, aged animals also elaborate the plastic change in SI. Training‐induced plasticity is associated with increased levels of GAD67 and GABA in SI. This may serve to attenuate the increased activity suggested by upregulation of Vglut1 and Vglut2 after training. In young animals, training also upregulates VGAT, which can further support GABAergic neurotransmission. In aged animals, probably due to a significant reduction in the VGAT mRNA level, the upregulation of VGAT expression after training is impossible, and that decreases the ability of the GABAergic system to effectively respond to increased demands on the inhibitory drive. Thus, aged mice require more time to elaborate the plastic change. GAD65 and GAD67 – glutamic acid decarboxylases; SYP – synaptophysin; VGAT – vesicular GABA transporter; Vglut1 and Vglut2 – vesicular glutamate transporters; CS – conditioned stimulus; UCS – unconditioned stimulus, 100% – expression level in young animals.
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References

    1. Abraham WC, et al (2008) Metaplasticity: tuning synapses and networks for plasticity. Nat. Rev. Neurosci. 9, 387. - PubMed
    1. Ahmadian SS, Rezvanian A, Peterson M, Weintraub S, Bigio EH, Mesulam MM, Geula C (2015) Loss of calbindin‐D28K is associated with the full range of tangle pathology within basal forebrain cholinergic neurons in Alzheimer's disease. Neurobiol. Aging 36, 3163–3170. - PMC - PubMed
    1. Akbarian S, Kim JJ, Potkin SG, Hagman JO, Tafazzoli A, Bunney WE, Jones EG (1995) Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics. Arch. Gen. Psychiatry 52, 258–266. - PubMed
    1. Ascoli GA, Alonso‐Nanclares L, Anderson SA, Barrionuevo G, Benavides‐Piccione R, Burkhalter A, Buzsáki G, Cauli B, Defelipe J, Fairén A, Feldmeyer D, Fishell G, Fregnac Y, Freund TF, Gardner D, Gardner EP, Goldberg JH, Helmstaedter M, Hestrin S, Karube F, Kisvárday ZF, Lambolez B, Lewis DA, Marin O, Markram H, Muñoz A, Packer A, Petersen CC, Rockland KS, Rossier J, Rudy B, Somogyi P, Staiger JF, Tamas G, Thomson AM, Toledo‐Rodriguez M, Wang Y, West DC, Yuste R. Group P. I. N. (2008) Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex. Nat. Rev. Neurosci. 9, 557–568. - PMC - PubMed
    1. Azpurua J, Eaton BA (2015) Neuronal epigenetics and the aging synapse. Front. Cell Neurosci. 9, 208. - PMC - PubMed

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