Heightened cortical excitability in aged rodents with memory impairment

Rebecca P. Haberman, Ming Teng Koh, Michela Gallagher

Research output: Contribution to journalArticle

Abstract

Elevated excitability in the hippocampus has emerged as a key contributor to reduced memory function in aging and in cognitive impairment prodromal to Alzheimer's disease. Here, we investigated the relationship between neural activity and memory in the hippocampus and a connectional cortical network using an aged rat model of individual differences for memory impairment. The expression of cFos was used as a measure of pharmacologically induced neural activity. Aged memory-impaired rats exhibited elevated cFos relative to young adult and aged unimpaired rats in the CA3 subfield of the hippocampus and in several cortical regions including the retrosplenial, parietal, and orbitofrontal cortices. Strong correlations between cFos intensity and task performance across the activated network showed a tight coupling between excitability and cognitive phenotype in aging. Elevated neural excitability extending beyond the hippocampus to interconnected posterior cortex (retrosplenial/parietal) was reduced by treatment with levetiracetam, a therapeutic with behavioral efficacy that has previously translated from rodent models of age-related impairment and Alzheimer's disease to humans with amnestic mild cognitive impairment.

Original languageEnglish (US)
JournalNeurobiology of Aging
DOIs
StateAccepted/In press - Oct 3 2016

Fingerprint

Rodentia
Hippocampus
Parietal Lobe
etiracetam
Alzheimer Disease
Task Performance and Analysis
Prefrontal Cortex
Individuality
Young Adult
Phenotype
Cortical Excitability
Therapeutics
Cognitive Dysfunction

Keywords

  • Aging
  • Hippocampal hyperactivity
  • Levetiracetam
  • Memory
  • Parietal cortex
  • Retrosplenial cortex

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology
  • Clinical Neurology

Cite this

Heightened cortical excitability in aged rodents with memory impairment. / Haberman, Rebecca P.; Koh, Ming Teng; Gallagher, Michela.

In: Neurobiology of Aging, 03.10.2016.

Research output: Contribution to journalArticle

@article{82022364eab84f3699fa0595f6839027,
title = "Heightened cortical excitability in aged rodents with memory impairment",
abstract = "Elevated excitability in the hippocampus has emerged as a key contributor to reduced memory function in aging and in cognitive impairment prodromal to Alzheimer's disease. Here, we investigated the relationship between neural activity and memory in the hippocampus and a connectional cortical network using an aged rat model of individual differences for memory impairment. The expression of cFos was used as a measure of pharmacologically induced neural activity. Aged memory-impaired rats exhibited elevated cFos relative to young adult and aged unimpaired rats in the CA3 subfield of the hippocampus and in several cortical regions including the retrosplenial, parietal, and orbitofrontal cortices. Strong correlations between cFos intensity and task performance across the activated network showed a tight coupling between excitability and cognitive phenotype in aging. Elevated neural excitability extending beyond the hippocampus to interconnected posterior cortex (retrosplenial/parietal) was reduced by treatment with levetiracetam, a therapeutic with behavioral efficacy that has previously translated from rodent models of age-related impairment and Alzheimer's disease to humans with amnestic mild cognitive impairment.",
keywords = "Aging, Hippocampal hyperactivity, Levetiracetam, Memory, Parietal cortex, Retrosplenial cortex",
author = "Haberman, {Rebecca P.} and Koh, {Ming Teng} and Michela Gallagher",
year = "2016",
month = "10",
day = "3",
doi = "10.1016/j.neurobiolaging.2016.12.021",
language = "English (US)",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Heightened cortical excitability in aged rodents with memory impairment

AU - Haberman, Rebecca P.

AU - Koh, Ming Teng

AU - Gallagher, Michela

PY - 2016/10/3

Y1 - 2016/10/3

N2 - Elevated excitability in the hippocampus has emerged as a key contributor to reduced memory function in aging and in cognitive impairment prodromal to Alzheimer's disease. Here, we investigated the relationship between neural activity and memory in the hippocampus and a connectional cortical network using an aged rat model of individual differences for memory impairment. The expression of cFos was used as a measure of pharmacologically induced neural activity. Aged memory-impaired rats exhibited elevated cFos relative to young adult and aged unimpaired rats in the CA3 subfield of the hippocampus and in several cortical regions including the retrosplenial, parietal, and orbitofrontal cortices. Strong correlations between cFos intensity and task performance across the activated network showed a tight coupling between excitability and cognitive phenotype in aging. Elevated neural excitability extending beyond the hippocampus to interconnected posterior cortex (retrosplenial/parietal) was reduced by treatment with levetiracetam, a therapeutic with behavioral efficacy that has previously translated from rodent models of age-related impairment and Alzheimer's disease to humans with amnestic mild cognitive impairment.

AB - Elevated excitability in the hippocampus has emerged as a key contributor to reduced memory function in aging and in cognitive impairment prodromal to Alzheimer's disease. Here, we investigated the relationship between neural activity and memory in the hippocampus and a connectional cortical network using an aged rat model of individual differences for memory impairment. The expression of cFos was used as a measure of pharmacologically induced neural activity. Aged memory-impaired rats exhibited elevated cFos relative to young adult and aged unimpaired rats in the CA3 subfield of the hippocampus and in several cortical regions including the retrosplenial, parietal, and orbitofrontal cortices. Strong correlations between cFos intensity and task performance across the activated network showed a tight coupling between excitability and cognitive phenotype in aging. Elevated neural excitability extending beyond the hippocampus to interconnected posterior cortex (retrosplenial/parietal) was reduced by treatment with levetiracetam, a therapeutic with behavioral efficacy that has previously translated from rodent models of age-related impairment and Alzheimer's disease to humans with amnestic mild cognitive impairment.

KW - Aging

KW - Hippocampal hyperactivity

KW - Levetiracetam

KW - Memory

KW - Parietal cortex

KW - Retrosplenial cortex

UR - http://www.scopus.com/inward/record.url?scp=85009830749&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85009830749&partnerID=8YFLogxK

U2 - 10.1016/j.neurobiolaging.2016.12.021

DO - 10.1016/j.neurobiolaging.2016.12.021

M3 - Article

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

ER -