Optogenetic Manipulation of Postsynaptic cAMP Using a Novel Transgenic Mouse Line Enables Synaptic Plasticity and Enhances Depolarization Following Tetanic Stimulation in the Hippocampal Dentate Gyrus.
Animals
Cyclic AMP
/ analysis
Dentate Gyrus
/ chemistry
Hippocampus
/ chemistry
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neuronal Plasticity
/ physiology
Optogenetics
/ methods
Organ Culture Techniques
Refractory Period, Electrophysiological
/ physiology
Synaptic Potentials
/ physiology
Synaptic Transmission
/ physiology
VSD imaging
cAMP
electrophysiology
long-term potentiation
optogenetics
photoactivatable adenylyl cyclase (PAC)
synaptic plasticity
Journal
Frontiers in neural circuits
ISSN: 1662-5110
Titre abrégé: Front Neural Circuits
Pays: Switzerland
ID NLM: 101477940
Informations de publication
Date de publication:
2020
2020
Historique:
received:
18
02
2020
accepted:
17
04
2020
entrez:
26
6
2020
pubmed:
26
6
2020
medline:
11
6
2021
Statut:
epublish
Résumé
cAMP is a positive regulator tightly involved in certain types of synaptic plasticity and related memory functions. However, its spatiotemporal roles at the synaptic and neural circuit levels remain elusive. Using a combination of a cAMP optogenetics approach and voltage-sensitive dye (VSD) imaging with electrophysiological recording, we define a novel capacity of postsynaptic cAMP in enabling dentate gyrus long-term potentiation (LTP) and depolarization in acutely prepared murine hippocampal slices. To manipulate cAMP levels at medial perforant path to granule neuron (MPP-DG) synapses by light, we generated transgenic (Tg) mice expressing photoactivatable adenylyl cyclase (PAC) in DG granule neurons. Using these Tg(CMV-Camk2a-RFP/bPAC)3Koka mice, we recorded field excitatory postsynaptic potentials (fEPSPs) from MPP-DG synapses and found that photoactivation of PAC during tetanic stimulation enabled synaptic potentiation that persisted for at least 30 min. This form of LTP was induced without the need for GABA receptor blockade that is typically required for inducing DG plasticity. The paired-pulse ratio (PPR) remained unchanged, indicating the cAMP-dependent LTP was likely postsynaptic. By employing fast fluorescent voltage-sensitive dye (VSD: di-4-ANEPPS) and fluorescence imaging, we found that photoactivation of the PAC actuator enhanced the intensity and extent of dentate gyrus depolarization triggered following tetanic stimulation. These results demonstrate that the elevation of cAMP in granule neurons is capable of rapidly enhancing synaptic strength and neuronal depolarization. The powerful actions of cAMP are consistent with this second messenger having a critical role in the regulation of synaptic function.
Identifiants
pubmed: 32581725
doi: 10.3389/fncir.2020.00024
pmc: PMC7283606
doi:
Substances chimiques
Cyclic AMP
E0399OZS9N
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
24Subventions
Organisme : CIHR
ID : MOP111220
Pays : Canada
Organisme : CIHR
ID : PJT 156103
Pays : Canada
Organisme : CIHR
ID : 154274
Pays : Canada
Informations de copyright
Copyright © 2020 Luyben, Rai, Li, Georgiou, Avila, Zhen, Collingridge, Tominaga and Okamoto.
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