Biophysical alterations of hippocampal pyramidal neurons in learning, ageing and Alzheimer's disease

John F. Disterhoft, Wendy Wu, Masuo Ohno

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

A series of behavioral, electrophysiological, and molecular biochemical experiments are reviewed indicating that when animals learn hippocampus- dependent tasks, output neurons in the CA1 and CA3 hippocampal subfields show reductions in the slow, post-burst afterhyperpolarization (AHP). The slow AHP is mediated by an apamin-insensitive calcium-activated potassium current. A reduction in the slow AHP makes hippocampal neurons more excitable and facilitates NMDA receptor-mediated response and temporal summation. During normal aging and in a mouse model of Alzheimer's disease (AD), the slow AHP is increased, making neurons less excitable and making learning more difficult. The subgroup of aging animals that are able to learn demonstrates the capacity to increase neuronal excitability by reducing the size of the slow AHP. Similarly, in a mouse model of AD, mice that are able to learn normally after a genetic alteration have a normal capacity for increasing hippocampal neuron excitability by reducing their slow AHP. We suggest that reduction in the slow AHP is basic to learning in young and aging animals. Inability to modulate the slow AHP contributes to learning deficits that occur during aging and early stages of AD.

Original languageEnglish (US)
Pages (from-to)383-406
Number of pages24
JournalAgeing Research Reviews
Volume3
Issue number4
DOIs
StatePublished - Nov 2004
Externally publishedYes

Fingerprint

Pyramidal Cells
Neurons
Alzheimer Disease
Aging of materials
Learning
Animals
Apamin
N-Methyl-D-Aspartate Receptors
Hippocampus
Potassium
Calcium
Experiments

Keywords

  • Afterdepolarization
  • Afterhyperpolarization
  • Calcium
  • Conditioning
  • Excitability

ASJC Scopus subject areas

  • Aging
  • Biochemistry

Cite this

Biophysical alterations of hippocampal pyramidal neurons in learning, ageing and Alzheimer's disease. / Disterhoft, John F.; Wu, Wendy; Ohno, Masuo.

In: Ageing Research Reviews, Vol. 3, No. 4, 11.2004, p. 383-406.

Research output: Contribution to journalArticle

Disterhoft, John F. ; Wu, Wendy ; Ohno, Masuo. / Biophysical alterations of hippocampal pyramidal neurons in learning, ageing and Alzheimer's disease. In: Ageing Research Reviews. 2004 ; Vol. 3, No. 4. pp. 383-406.
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