Age-related changes in tonic activation of presynaptic versus extrasynaptic γ-amniobutyric acid type B receptors in rat medial prefrontal cortex

The present study examined the effect of age on both glutamatergic and γ-aminobutyric acid mediated (GABAergic) signaling in the rodent medial prefrontal cortex (mPFC), with an emphasis on revealing novel changes contributing to increased inhibition in age. Whole-cell patch clamp recordings were obt...

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Bibliographic Details
Published in:Neurobiology of aging 2016-09, Vol.45, p.88-97
Main Authors: Carpenter, Haley E., Kelly, Kyle B., Bizon, Jennifer L., Frazier, Charles J.
Format: Article
Language:English
Subjects:
Age-related cognitive decline
Aging - metabolism
Aging - psychology
Animals
Beclomethasone
Cognition
Executive Function
GABAA
GABAB
gamma-Aminobutyric Acid - physiology
L2/3 pyramidal neurons
Male
Neural Inhibition
Patch-Clamp Techniques
Prefrontal cortex
Prefrontal Cortex - metabolism
Pyramidal Cells - physiology
Rats, Inbred F344
Receptors, GABA - metabolism
Receptors, GABA-B - metabolism
Receptors, GABA-B - physiology
Receptors, Presynaptic - metabolism
Signal Transduction - physiology
Working memory
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Summary:The present study examined the effect of age on both glutamatergic and γ-aminobutyric acid mediated (GABAergic) signaling in the rodent medial prefrontal cortex (mPFC), with an emphasis on revealing novel changes contributing to increased inhibition in age. Whole-cell patch clamp recordings were obtained from layer 2/3 mPFC pyramidal neurons in acute cortical slices prepared from either young (4 months) or aged (20–24 months) male F344 rats. Results indicated that GABAB receptors on GABAergic, but not on glutamatergic, inputs to layer 2/3 pyramidal cells are tonically activated by ambient GABA in young animals and further demonstrated that this form of tonic inhibition is significantly attenuated in aged mPFC. Moreover, concurrent with loss of tonic presynaptic GABAB autoreceptor activation, layer 2/3 pyramidal cells in aged mPFC are subjected to increased tonic activation of extrasynaptic GABAA and GABAB receptors. These data demonstrate a shift in the site of GABAB receptor-mediated inhibitory tone in the aged mPFC that clearly promotes increased inhibition of pyramidal cells in aged animals, and that may plausibly contribute to impaired executive function.
ISSN:0197-4580
1558-1497
DOI:10.1016/j.neurobiolaging.2016.05.015