LTP at Hilar Mossy Cell-Dentate Granule Cell Synapses Modulates Dentate Gyrus Output by Increasing Excitation/Inhibition Balance

Yuki Hashimotodani, Kaoutsar Nasrallah, Kyle R. Jensen, Andrés E. Chávez, Daniel Carrera, Pablo E. Castillo

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Excitatory hilar mossy cells (MCs) in the dentate gyrus receive inputs from dentate granule cells (GCs) and project back to GCs locally, contralaterally, and along the longitudinal axis of the hippocampus, thereby establishing an associative positive-feedback loop and connecting functionally diverse hippocampal areas. MCs also synapse with GABAergic interneurons that mediate feed-forward inhibition onto GCs. Surprisingly, although these circuits have been implicated in both memory formation (e.g., pattern separation) and temporal lobe epilepsy, little is known about activity-dependent plasticity of their synaptic connections. Here, we report that MC-GC synapses undergo a presynaptic, NMDA-receptor-independent form of long-term potentiation (LTP) that requires postsynaptic brain-derived neurotrophic factor (BDNF)/TrkB and presynaptic cyclic AMP (cAMP)/PKA signaling. This LTP is input specific and selectively expressed at MC-GC synapses, but not at the disynaptic inhibitory loop. By increasing the excitation/inhibition balance, MC-GC LTP enhances GC output at the associative MC-GC recurrent circuit and may contribute to dentate-dependent forms of learning and epilepsy.

Original languageEnglish (US)
Pages (from-to)928-943.e3
JournalNeuron
Volume95
Issue number4
DOIs
StatePublished - Aug 16 2017

Fingerprint

Long-Term Potentiation
Dentate Gyrus
Synapses
Inhibition (Psychology)
Presynaptic Receptors
Neuronal Plasticity
Temporal Lobe Epilepsy
Brain-Derived Neurotrophic Factor
Interneurons
N-Methyl-D-Aspartate Receptors
Cyclic AMP
Epilepsy
Hippocampus

Keywords

  • BDNF
  • CA3
  • hippocampus
  • learning
  • memory
  • pattern separation
  • presynaptic
  • TrkB

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

LTP at Hilar Mossy Cell-Dentate Granule Cell Synapses Modulates Dentate Gyrus Output by Increasing Excitation/Inhibition Balance. / Hashimotodani, Yuki; Nasrallah, Kaoutsar; Jensen, Kyle R.; Chávez, Andrés E.; Carrera, Daniel; Castillo, Pablo E.

In: Neuron, Vol. 95, No. 4, 16.08.2017, p. 928-943.e3.

Research output: Contribution to journalArticle

Hashimotodani, Yuki ; Nasrallah, Kaoutsar ; Jensen, Kyle R. ; Chávez, Andrés E. ; Carrera, Daniel ; Castillo, Pablo E. / LTP at Hilar Mossy Cell-Dentate Granule Cell Synapses Modulates Dentate Gyrus Output by Increasing Excitation/Inhibition Balance. In: Neuron. 2017 ; Vol. 95, No. 4. pp. 928-943.e3.
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