Cited by 384Neurogenesis and neuroplasticity mechanismsMemory and Neural MechanismsDeep Brain Stimulation and Movement Disorders

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Stimulation of Entorhinal Cortex Promotes Adult Neurogenesis and Facilitates Spatial Memory

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Stone, Scellig S. D., Teixeira, Cátia M., DeVito, Loren M., Zaslavsky, Kirill, Josselyn, Sheena A., Lozano, Andres M., Frankland, Paul W.·2011·The Journal of Neuroscience

DOI 10.1523/jneurosci.3100-11.2011PMC PMC6623309

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Abstract

Deep brain stimulation (DBS) is an established therapeutic modality for the treatment of movement disorders and an emerging therapeutic approach for the treatment of disorders of mood and thought. For example, recently we have shown that DBS of the fornix may ameliorate cognitive decline associated with dementia. However, like other applications of DBS, the mechanisms mediating these clinical effects are unknown. As DBS modulates neurophysiological activity in targeted brain regions, DBS might influence cognitive function via activity-dependent regulation of hippocampal neurogenesis. Using stimulation parameters analogous to clinical high-frequency DBS, here we addressed this question in mice. We found that acute stimulation of the entorhinal cortex (EC) transiently promoted proliferation in the dentate gyrus (DG). Cells generated as a consequence of stimulation differentiated into neurons, survived for at least several weeks, and acquired normal dentate granule cell (DGC) morphology. Importantly, stimulation-induced promotion of neurogenesis was limited to the DG and not associated with changes in apoptotic cell death. Using immunohistochemical approaches, we found that, once sufficiently mature, these stimulation-induced neurons integrated into hippocampal circuits supporting water-maze memory. Finally, formation of water-maze memory was facilitated 6 weeks (but not 1 week) after bilateral stimulation of the EC. The delay-dependent nature of these effects matches the maturation-dependent integration of adult-generated DGCs into dentate circuits supporting water-maze memory. Furthermore, because the beneficial effects of EC stimulation were prevented by blocking neurogenesis, this suggests a causal relationship between stimulation-induced promotion of adult neurogenesis and enhanced spatial memory.

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Authors: Stone, S. S. D., Teixeira, C. M., DeVito, L. M., Zaslavsky, K., Josselyn, S. A., Lozano, A. M., & Frankland, P. W.
Affiliations: Hospital for Sick Children (CA)
Universidade do Porto (PT)
University of Toronto (CA)
Corresponding author: Frankland, Paul W.
ORCID: Stone, Scellig S. D.
Teixeira, Cátia M.
Zaslavsky, Kirill
Josselyn, Sheena A.
Frankland, Paul W.
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2011-09-21
Volume: 31
Issue: 38
Pages: 13469-13484
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.3100-11.2011
PMC: PMC6623309
OpenAlex: W2132668024
Cited by: 384
References: 68
Citations by year: 2026: 12 · 2025: 8 · 2024: 18 · 2023: 16 · 2022: 24 · 2021: 32 · 2020: 27 · 2019: 24 · 2018: 27 · 2017: 21 · 2016: 38 · 2015: 41 · 2014: 24 · 2013: 30 · 2012: 39
FWCI: 10.08
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 182 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: University of Toronto
Canadian Institutes of Health Research (MOP- 86762, 102234_1)
Topics: Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Health Sciences › Medicine › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
Keywords: entorhinal cortex, deep brain stimulation, adult neurogenesis, dentate gyrus, dentate gyrus granule cells, spatial memory, cell proliferation, neuronal differentiation, apoptosis
MeSH terms: Animals, Cell Survival, Memory, Mice, Inbred Strains, Neural Pathways, Neurons, Spatial Behavior, Time Factors, Apoptosis, Entorhinal Cortex, Maze Learning, Dentate Gyrus, Deep Brain Stimulation, Mice, Neurogenesis, Neuroanatomical Tract-Tracing Techniques

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Stimulation of Entorhinal Cortex Promotes Adult Neurogenesis and Facilitates Spatial Memory

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