Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Oct:164:107069.
doi: 10.1016/j.nlm.2019.107069. Epub 2019 Aug 20.

Regulation of intrinsic excitability: Roles for learning and memory, aging and Alzheimer's disease, and genetic diversity

Amy R Dunn  1 , Catherine C Kaczorowski  1
Affiliations
Review

Regulation of intrinsic excitability: Roles for learning and memory, aging and Alzheimer's disease, and genetic diversity

Amy R Dunn et al. Neurobiol Learn Mem. 2019 Oct.

Abstract

Plasticity of intrinsic neuronal excitability facilitates learning and memory across multiple species, with aberrant modulation of this process being linked to the development of neurological symptoms in models of cognitive aging and Alzheimer's disease. Learning-related increases in intrinsic excitability of neurons occurs in a variety of brain regions, and is generally thought to promote information processing and storage through enhancement of synaptic throughput and induction of synaptic plasticity. Experience-dependent changes in intrinsic neuronal excitability rely on activity-dependent gene expression patterns, which can be influenced by genetic and environmental factors, aging, and disease. Reductions in baseline intrinsic excitability, as well as aberrant plasticity of intrinsic neuronal excitability and in some cases pathological hyperexcitability, have been associated with cognitive deficits in animal models of both normal cognitive aging and Alzheimer's disease. Genetic factors that modulate plasticity of intrinsic excitability likely underlie individual differences in cognitive function and susceptibility to cognitive decline. Thus, targeting molecular mediators that either control baseline intrinsic neuronal excitability, subserve learning-related intrinsic neuronal plasticity, and/or promote resilience may be a promising therapeutic strategy for maintaining cognitive function in aging and disease. In this review, we discuss the complementary relationship between intrinsic excitability and learning, with a particular focus on how this relationship varies as a function of age, disease state, and genetic make-up, and how targeting these factors may help to further elucidate our understanding of the role of intrinsic excitability in cognitive function and cognitive decline.

Keywords: Aging; Alzheimer’s disease; Genetic diversity; Hippocampus; Intrinsic excitability; Learning and memory.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Abraham WC (2003). “How long will long-term potentiation last?” Philos Trans R Soc Lond B Biol Sci 358(1432): 735–744. - PMC - PubMed
    1. Amatniek JC, Hauser WA, DelCastillo-Castaneda C, Jacobs DM, Marder K and Bell K (2006). “Incidence and predictors of seizures in patients with Alzheimer’s disesase.” Epilepsia 47(5): 867–872. - PubMed
    1. Bakker A, Krauss GL, Albert MS, Speck CL, Jones LR, Stark CE, Yassa MA, Bassett SS, Shelton AL and Gallagher M (2012). “Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment.” Neuron 74(3): 467–474. - PMC - PubMed
    1. Belmeguenai A, Hosy E, Bengtsson F, Pedroarena CM, Piochon C, Teuling E, He Q, Ohtsuki G, De Jeu MT, Elgersma Y, De Zeeuw CI, Jorntell H and Hansel C (2010). “Intrinsic plasticity complements long-term potentiation in parallel fiber input gain control in cerebellar Purkinje cells.” J Neurosci 30(41): 13630–13643. - PMC - PubMed
    1. Berridge MJ (1998). “Neuronal calcium signaling.” Neuron 21: 13–26. - PubMed

Publication types