Distinct Modulation of by Synaptic Potentiation in Excitatory and Inhibitory Neurons

Overview

Journal eNeuro

Specialty Neurology

Date 2024 Oct 15

PMID 39406481

Authors

Lotte J Herstel

Corette J Wierenga

Affiliations

Soon will be listed here.

Abstract

Selective modifications in the expression or function of dendritic ion channels regulate the propagation of synaptic inputs and determine the intrinsic excitability of a neuron. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels open upon membrane hyperpolarization and conduct a depolarizing inward current ( ). HCN channels are enriched in the dendrites of hippocampal pyramidal neurons where they regulate the integration of synaptic inputs. Synaptic plasticity can bidirectionally modify dendritic HCN channels in excitatory neurons depending on the strength of synaptic potentiation. In inhibitory neurons, however, the dendritic expression and modulation of HCN channels are largely unknown. In this study, we systematically compared the modulation of by synaptic potentiation in hippocampal CA1 pyramidal neurons and stratum radiatum (sRad) interneurons in mouse organotypic cultures. properties were similar in inhibitory and excitatory neurons and contributed to resting membrane potential and action potential firing. We found that in sRad interneurons, HCN channels were downregulated after synaptic plasticity, irrespective of the strength of synaptic potentiation. This suggests differential regulation of in excitatory and inhibitory neurons, possibly signifying their distinct role in network activity.

References

Magee J . Dendritic lh normalizes temporal summation in hippocampal CA1 neurons. Nat Neurosci. 1999; 2(6):508-14. DOI: 10.1038/9158. View

Kaneko M, Takahashi T . Presynaptic mechanism underlying cAMP-dependent synaptic potentiation. J Neurosci. 2004; 24(22):5202-8. PMC: 6729197. DOI: 10.1523/JNEUROSCI.0999-04.2004. View

De Simoni A, Griesinger C, Edwards F . Development of rat CA1 neurones in acute versus organotypic slices: role of experience in synaptic morphology and activity. J Physiol. 2003; 550(Pt 1):135-47. PMC: 2343027. DOI: 10.1113/jphysiol.2003.039099. View

Ma L, Jongbloets B, Xiong W, Melander J, Qin M, Lameyer T . A Highly Sensitive A-Kinase Activity Reporter for Imaging Neuromodulatory Events in Awake Mice. Neuron. 2018; 99(4):665-679.e5. PMC: 6152931. DOI: 10.1016/j.neuron.2018.07.020. View

Veres J, Andrasi T, Nagy-Pal P, Hajos N . CaMKIIα Promoter-Controlled Circuit Manipulations Target Both Pyramidal Cells and Inhibitory Interneurons in Cortical Networks. eNeuro. 2023; 10(4). PMC: 10088982. DOI: 10.1523/ENEURO.0070-23.2023. View

Hengen K, Torrado Pacheco A, McGregor J, Van Hooser S, Turrigiano G . Neuronal Firing Rate Homeostasis Is Inhibited by Sleep and Promoted by Wake. Cell. 2016; 165(1):180-191. PMC: 4809041. DOI: 10.1016/j.cell.2016.01.046. View

Maki-Marttunen T, Maki-Marttunen V . Excitatory and inhibitory effects of HCN channel modulation on excitability of layer V pyramidal cells. PLoS Comput Biol. 2022; 18(9):e1010506. PMC: 9506642. DOI: 10.1371/journal.pcbi.1010506. View

Wainger B, DeGennaro M, Santoro B, Siegelbaum S, Tibbs G . Molecular mechanism of cAMP modulation of HCN pacemaker channels. Nature. 2001; 411(6839):805-10. DOI: 10.1038/35081088. View

Fan Y, Fricker D, Brager D, Chen X, Lu H, Chitwood R . Activity-dependent decrease of excitability in rat hippocampal neurons through increases in I(h). Nat Neurosci. 2005; 8(11):1542-51. DOI: 10.1038/nn1568. View

10.

Oz O, Matityahu L, Mizrahi-Kliger A, Kaplan A, Berkowitz N, Tiroshi L . Non-uniform distribution of dendritic nonlinearities differentially engages thalamostriatal and corticostriatal inputs onto cholinergic interneurons. Elife. 2022; 11. PMC: 9302969. DOI: 10.7554/eLife.76039. View

11.

Lupica C, Bell J, Hoffman A, Watson P . Contribution of the hyperpolarization-activated current (I(h)) to membrane potential and GABA release in hippocampal interneurons. J Neurophysiol. 2001; 86(1):261-8. DOI: 10.1152/jn.2001.86.1.261. View

12.

Maccaferri G, McBain C . The hyperpolarization-activated current (Ih) and its contribution to pacemaker activity in rat CA1 hippocampal stratum oriens-alveus interneurones. J Physiol. 1996; 497 ( Pt 1):119-30. PMC: 1160917. DOI: 10.1113/jphysiol.1996.sp021754. View

13.

Zemankovics R, Kali S, Paulsen O, Freund T, Hajos N . Differences in subthreshold resonance of hippocampal pyramidal cells and interneurons: the role of h-current and passive membrane characteristics. J Physiol. 2010; 588(Pt 12):2109-32. PMC: 2905616. DOI: 10.1113/jphysiol.2009.185975. View

14.

Carvalho T, Buonomano D . Differential effects of excitatory and inhibitory plasticity on synaptically driven neuronal input-output functions. Neuron. 2009; 61(5):774-85. PMC: 2676350. DOI: 10.1016/j.neuron.2009.01.013. View

15.

van Welie I, van Hooft J, Wadman W . Homeostatic scaling of neuronal excitability by synaptic modulation of somatic hyperpolarization-activated Ih channels. Proc Natl Acad Sci U S A. 2004; 101(14):5123-8. PMC: 387384. DOI: 10.1073/pnas.0307711101. View

16.

Dini L, Del Lungo M, Resta F, Melchiorre M, Spinelli V, Di Cesare Mannelli L . Selective Blockade of HCN1/HCN2 Channels as a Potential Pharmacological Strategy Against Pain. Front Pharmacol. 2018; 9:1252. PMC: 6237106. DOI: 10.3389/fphar.2018.01252. View

17.

Zolles G, Klocker N, Wenzel D, Weisser-Thomas J, Fleischmann B, Roeper J . Pacemaking by HCN channels requires interaction with phosphoinositides. Neuron. 2006; 52(6):1027-36. DOI: 10.1016/j.neuron.2006.12.005. View

18.

Zhang W, Linden D . The other side of the engram: experience-driven changes in neuronal intrinsic excitability. Nat Rev Neurosci. 2003; 4(11):885-900. DOI: 10.1038/nrn1248. View

19.

Carzoli K, Kogias G, Fawcett-Patel J, Liu S . Cerebellar interneurons control fear memory consolidation via learning-induced HCN plasticity. Cell Rep. 2023; 42(9):113057. PMC: 10616818. DOI: 10.1016/j.celrep.2023.113057. View

20.

Keaveney M, Rahsepar B, Tseng H, Fernandez F, Mount R, Ta T . CaMKIIα-Positive Interneurons Identified via a microRNA-Based Viral Gene Targeting Strategy. J Neurosci. 2020; 40(50):9576-9588. PMC: 7726537. DOI: 10.1523/JNEUROSCI.2570-19.2020. View