Imbalance towards inhibition as a substrate of aging-associated cognitive impairment.
The number of synapses in the cerebral cortex decreases with aging. However, how this structural change translates into the cognitive impairment observed in aged animals remains unknown. Aged animals are not a homogenous group with respect to their cognitive performances; but instead, they can be separated into aged cognitively unimpaired ("normal") and aged cognitively impaired groups using a spatial memory task such as the Morris water maze. These two aged groups provide an unprecedented opportunity to isolate synaptic properties that relate to cognitive impairment from unrelated factors associated with normal aging. Using such classification, we conducted whole-cell patch-clamp recordings to measure basal spontaneous miniature excitatory (mEPSCs) and inhibitory synaptic currents (mIPSCs) bombarding layer V pyramidal neurons in the parietal cortex. We found that the frequencies of both mEPSC and mIPSC were lower in aged normal rats when compared with young rats. In contrast, aged cognitively impaired rats displayed a reduction in mEPSC frequency only. This results in an imbalance towards inhibition that may be an important substrate of the cognitive impairment in aged animals. We also found that pyramidal neurons in both aged normal and aged cognitively impaired rats exhibit similar structural attritions. Thus, cognitive impairment may be more related to an altered balance between different neurotransmitter systems than a mere reduction in synaptic structures.
Wong
Tak Pan
TP
Department of Pharmacology and Therapeutics, McGill University, Montréal, Que., Canada H3G 1Y6.
Marchese
Giorgio
G
Casu
Maria Antonietta
MA
Ribeiro-da-Silva
Alfredo
A
Cuello
A Claudio
AC
De Koninck
Yves
Y
D000200:Action Potentials / Q000502:physiology / Q000528:radiation effects; D000375:Aging / Q000473:pathology / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D003072:Cognition Disorders / Q000503:physiopathology*; D004558:Electric Stimulation / Q000379:methods; D004924:Escape Reaction / Q000502:physiology; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010296:Parietal Lobe / Q000166:cytology; D018408:Patch-Clamp Techniques; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D011930:Reaction Time / Q000502:physiology; D013037:Spatial Behavior / Q000502:physiology