title: Integrity of mGluR-LTD in the associative/commissural inputs to CA3 correlates with successful aging in rats.
abstract: The impact of aging on cognitive capabilities varies among individuals ranging from significant impairment to preservation of function on par with younger adults. Research on the neural basis for age-related memory decline has focused primarily on the CA1 region of the hippocampus. However, recent studies in elderly human and rodents indicate that individual differences in cognitive aging are more strongly tied to functional alterations in CA3 circuits. To examine synaptic plasticity in the CA3 region, we used aged rats behaviorally characterized in a hippocampal-dependent task to evaluate the status of long-term potentiation and long-term depression (LTP and LTD) in the associative/commissural pathway (A/C → CA3), which provides the majority of excitatory input to CA3 pyramidal neurons. We found that, unlike in CA1 synapses, in A/C → CA3 LTP is minimally affected by age. However, two forms of LTD, involving NMDA and metabotropic glutamate receptors (mGluR), are both greatly reduced in age-impaired rats. Age-unimpaired rats, in contrast, had intact mGluR LTD. These findings indicate that the integrity of mGluR-LTD at A/C → CA3 inputs may play a crucial role in maintaining the performance of CA3 circuitry in aging.
authors.affiliation: The Mind/Brain Institute, Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Sunggu
authors.initials: S
authors.lastname: Yang
authors.forename: Andrea
authors.initials: A
authors.lastname: Megill
authors.forename: Alvaro O
authors.initials: AO
authors.lastname: Ardiles
authors.forename: Sarah
authors.initials: S
authors.lastname: Ransom
authors.forename: Trinh
authors.initials: T
authors.lastname: Tran
authors.forename: Ming Teng
authors.initials: MT
authors.lastname: Koh
authors.forename: Hey-Kyoung
authors.initials: HK
authors.lastname: Lee
authors.forename: Michela
authors.initials: M
authors.lastname: Gallagher
authors.forename: Alfredo
authors.initials: A
authors.lastname: Kirkwood
mesh_terms: D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D001703:Biophysics; D056654:CA3 Region, Hippocampal / Q000166:cytology*; D003521:Cyclopropanes / Q000494:pharmacology; D004558:Electric Stimulation; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009415:Nerve Net / Q000187:drug effects / Q000473:pathology; D009433:Neural Inhibition; D017966:Pyramidal Cells; D051381:Rats; D020318:Rats, Long-Evans; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D013550:Swimming; D013569:Synapses / Q000502:physiology*
chemical_list: D003521:Cyclopropanes; D018683:Excitatory Amino Acid Agents; D018094:Receptors, Metabotropic Glutamate; C082313:2-(2,3-dicarboxycyclopropyl)glycine; D005998:Glycine
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