» Articles » PMID: 25637803

Synapse-specific Compartmentalization of Signaling Cascades for LTP Induction in CA3 Interneurons

Overview
Journal Neuroscience
Specialty Neurology
Date 2015 Feb 1
PMID 25637803
Citations 9
Authors
Affiliations
Soon will be listed here.
Abstract

Inhibitory interneurons with somata in strata radiatum and lacunosum-molecular (SR/L-M) of hippocampal area CA3 receive excitatory input from pyramidal cells via the recurrent collaterals (RCs), and the dentate gyrus granule cells via the mossy fibers (MFs). Here we demonstrate that Hebbian long-term potentiation (LTP) at RC synapses on SR/L-M interneurons requires the concomitant activation of calcium-impermeable AMPARs (CI-AMPARs) and N-methyl-d-aspartate receptors (NMDARs). RC LTP was prevented by voltage clamping the postsynaptic cell during high-frequency stimulation (HFS; 3 trains of 100 pulses delivered at 100 Hz every 10s), with intracellular injections of the Ca(2+) chelator BAPTA (20mM), and with the NMDAR antagonist D-AP5. In separate experiments, RC and MF inputs converging onto the same interneuron were sequentially activated. We found that RC LTP induction was blocked by inhibitors of the calcium/calmodulin-dependent protein kinase II (CaMKII; KN-62, 10 μM or KN-93, 10 μM) but MF LTP was CaMKII independent. Conversely, the application of the protein kinase A (PKA) activators forskolin/IBMX (50 μM/25 μM) potentiated MF EPSPs but not RC EPSPs. Together these data indicate that the aspiny dendrites of SR/L-M interneurons compartmentalize synapse-specific Ca(2+) signaling required for LTP induction at RC and MF synapses. We also show that the two signal transduction cascades converge to activate a common effector, protein kinase C (PKC). Specifically, LTP at RC and MF synapses on the same SR/LM interneuron was blocked by postsynaptic injections of chelerythrine (10 μM). These data indicate that both forms of LTP share a common mechanism involving PKC-dependent signaling modulation.

Citing Articles

BDNF and Lactate as Modulators of Hippocampal CA3 Network Physiology.

Griego E, Galvan E Cell Mol Neurobiol. 2023; 43(8):4007-4022.

PMID: 37874456 PMC: 11407739. DOI: 10.1007/s10571-023-01425-6.


Long-term potentiation in neurogliaform interneurons modulates excitation-inhibition balance in the temporoammonic pathway.

Mercier M, Magloire V, Cornford J, Kullmann D J Physiol. 2022; 600(17):4001-4017.

PMID: 35876215 PMC: 9540908. DOI: 10.1113/JP282753.


Synaptic Plasticity in Cortical Inhibitory Neurons: What Mechanisms May Help to Balance Synaptic Weight Changes?.

Bannon N, Chistiakova M, Volgushev M Front Cell Neurosci. 2020; 14:204.

PMID: 33100968 PMC: 7500144. DOI: 10.3389/fncel.2020.00204.


Loss of function of NCOR1 and NCOR2 impairs memory through a novel GABAergic hypothalamus-CA3 projection.

Zhou W, He Y, Rehman A, Kong Y, Hong S, Ding G Nat Neurosci. 2019; 22(2):205-217.

PMID: 30664766 PMC: 6361549. DOI: 10.1038/s41593-018-0311-1.


Mechanisms of Supralinear Calcium Integration in Dendrites of Hippocampal CA1 Fast-Spiking Cells.

Camire O, Lazarevich I, Gilbert T, Topolnik L Front Synaptic Neurosci. 2019; 10:47.

PMID: 30618708 PMC: 6297674. DOI: 10.3389/fnsyn.2018.00047.


References
1.
Chitwood R, Hubbard A, Jaffe D . Passive electrotonic properties of rat hippocampal CA3 interneurones. J Physiol. 1999; 515 ( Pt 3):743-56. PMC: 2269181. DOI: 10.1111/j.1469-7793.1999.743ab.x. View

2.
Poncer J, Esteban J, Malinow R . Multiple mechanisms for the potentiation of AMPA receptor-mediated transmission by alpha-Ca2+/calmodulin-dependent protein kinase II. J Neurosci. 2002; 22(11):4406-11. PMC: 6758819. DOI: 20026449. View

3.
Lu F, Hawkins R . Presynaptic and postsynaptic Ca(2+) and CamKII contribute to long-term potentiation at synapses between individual CA3 neurons. Proc Natl Acad Sci U S A. 2006; 103(11):4264-9. PMC: 1449681. DOI: 10.1073/pnas.0508162103. View

4.
Salin P, Scanziani M, Malenka R, Nicoll R . Distinct short-term plasticity at two excitatory synapses in the hippocampus. Proc Natl Acad Sci U S A. 1996; 93(23):13304-9. PMC: 24088. DOI: 10.1073/pnas.93.23.13304. View

5.
Fellini L, Florian C, Courtey J, Roullet P . Pharmacological intervention of hippocampal CA3 NMDA receptors impairs acquisition and long-term memory retrieval of spatial pattern completion task. Learn Mem. 2009; 16(6):387-94. DOI: 10.1101/lm.1433209. View