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 language | English (US) |
|---|---|
| Pages (from-to) | 928-943.e3 |
| Journal | Neuron |
| Volume | 95 |
| Issue number | 4 |
| DOIs | |
| State | Published - Aug 16 2017 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - LTP at Hilar Mossy Cell-Dentate Granule Cell Synapses Modulates Dentate Gyrus Output by Increasing Excitation/Inhibition Balance
AU - Hashimotodani, Yuki
AU - Nasrallah, Kaoutsar
AU - Jensen, Kyle R.
AU - Chávez, Andrés E.
AU - Carrera, Daniel
AU - Castillo, Pablo E.
PY - 2017/8/16
Y1 - 2017/8/16
N2 - 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.
AB - 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.
KW - BDNF
KW - CA3
KW - hippocampus
KW - learning
KW - memory
KW - pattern separation
KW - presynaptic
KW - TrkB
UR - http://www.scopus.com/inward/record.url?scp=85027340063&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85027340063&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2017.07.028
DO - 10.1016/j.neuron.2017.07.028
M3 - Article
VL - 95
SP - 928-943.e3
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 4
ER -