Adult neurogenesis modifies excitability of the dentate gyrus

Taruna Ikrar, Nannan Guo, Kaiwen He, Antoine Besnard, Sally Levinson, Alexis Hill, Hey-Kyoung Lee, Rene Hen, Xiangmin Xu, Amar Sahay

Research output: Contribution to journalArticle

Abstract

Adult-born dentate granule neurons contribute to memory encoding functions of the dentate gyrus (DG) such as pattern separation. However, local circuit-mechanisms by which adult-born neurons partake in this process are poorly understood. Computational, neuroanatomical and electrophysiological studies suggest that sparseness of activation in the granule cell layer (GCL) is conducive for pattern separation. A sparse coding scheme is thought to facilitate the distribution of similar entorhinal inputs across the GCL to decorrelate overlapping representations and minimize interference. Here we used fast voltage-sensitive dye (VSD) imaging combined with laser photostimulation and electrical stimulation to examine how selectively increasing adult DG neurogenesis influences local circuit activity and excitability. We show that DG of mice with more adult-born neurons exhibits decreased strength of neuronal activation and more restricted excitation spread in GCL while maintaining effective output to CA3c. Conversely, blockade of adult hippocampal neurogenesis changed excitability of the DG in the opposite direction. Analysis of GABAergic inhibition onto mature dentate granule neurons in the DG of mice with more adult-born neurons shows a modest readjustment of perisomatic inhibitory synaptic gain without changes in overall inhibitory tone, presynaptic properties or GABAergic innervation pattern. Retroviral labeling of connectivity in mice with more adult-born neurons showed increased number of excitatory synaptic contacts of adult-born neurons onto hilar interneurons. Together, these studies demonstrate that adult hippocampal neurogenesis modifies excitability of mature dentate granule neurons and that this non-cell autonomous effect may be mediated by local circuit mechanisms such as excitatory drive onto hilar interneurons. Modulation of DG excitability by adult-born dentate granule neurons may enhance sparse coding in the GCL to influence pattern separation.

Original languageEnglish (US)
Article number204
JournalFrontiers in Neural Circuits
Volume7
Issue numberDEC
DOIs
StatePublished - Dec 26 2013

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Neurogenesis
Dentate Gyrus
Neurons
Interneurons
Voltage-Sensitive Dye Imaging
Electric Stimulation
Lasers

Keywords

  • Adult neurogenesis
  • Dentate granule neurons
  • Dentate gyrus
  • Encoding
  • Excitability
  • Inhibition
  • Pattern separation

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Cellular and Molecular Neuroscience
  • Sensory Systems
  • Cognitive Neuroscience

Cite this

Ikrar, T., Guo, N., He, K., Besnard, A., Levinson, S., Hill, A., ... Sahay, A. (2013). Adult neurogenesis modifies excitability of the dentate gyrus. Frontiers in Neural Circuits, 7(DEC), [204]. https://doi.org/10.3389/fncir.2013.00204

Adult neurogenesis modifies excitability of the dentate gyrus. / Ikrar, Taruna; Guo, Nannan; He, Kaiwen; Besnard, Antoine; Levinson, Sally; Hill, Alexis; Lee, Hey-Kyoung; Hen, Rene; Xu, Xiangmin; Sahay, Amar.

In: Frontiers in Neural Circuits, Vol. 7, No. DEC, 204, 26.12.2013.

Research output: Contribution to journalArticle

Ikrar, T, Guo, N, He, K, Besnard, A, Levinson, S, Hill, A, Lee, H-K, Hen, R, Xu, X & Sahay, A 2013, 'Adult neurogenesis modifies excitability of the dentate gyrus', Frontiers in Neural Circuits, vol. 7, no. DEC, 204. https://doi.org/10.3389/fncir.2013.00204
Ikrar T, Guo N, He K, Besnard A, Levinson S, Hill A et al. Adult neurogenesis modifies excitability of the dentate gyrus. Frontiers in Neural Circuits. 2013 Dec 26;7(DEC). 204. https://doi.org/10.3389/fncir.2013.00204
Ikrar, Taruna ; Guo, Nannan ; He, Kaiwen ; Besnard, Antoine ; Levinson, Sally ; Hill, Alexis ; Lee, Hey-Kyoung ; Hen, Rene ; Xu, Xiangmin ; Sahay, Amar. / Adult neurogenesis modifies excitability of the dentate gyrus. In: Frontiers in Neural Circuits. 2013 ; Vol. 7, No. DEC.
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