Homeostatic plasticity and burst activity are mediated by hyperpolarization-activated cation currents and T-type calcium channels in neuronal cultures.

ABSTRACT: Homeostatic plasticity stabilizes neuronal networks by adjusting the responsiveness of neurons according to their global activity and the intensity of the synaptic inputs. We investigated the homeostatic regulation of hyperpolarization-activated cyclic nucleotide-gated (HCN) and T-type calcium (Ca_V3) channels in dissociated and organotypic slice cultures. After 48 h blocking of neuronal activity by tetrodotoxin (TTX), our patch-clamp experiments revealed an increase in the depolarizing voltage sag and post-inhibitory rebound mediated by HCN and Ca_V3 channels, respectively. All HCN subunits (HCN1 to 4) and T-type Ca-channel subunits (Ca_V3.1, 3.2 and 3.3) were expressed in both control and activity-deprived hippocampal cultures. Elevated expression levels of Ca_V3.1 mRNA and a selective increase in the expression of TRIP8b exon 4 isoforms, known to regulate HCN channel localization, were also detected in TTX-treated cultured hippocampal neurons. Immunohistochemical staining in TTX-treated organotypic slices verified a more proximal translocation of HCN1 channels in CA1 pyramidal neurons. Computational modeling also implied that HCN and T-type calcium channels have important role in the regulation of synchronized bursting evoked by previous activity-deprivation. Thus, our findings indicate that HCN and T-type Ca-channels contribute to the homeostatic regulation of excitability and integrative properties of hippocampal neurons.

SUBMITTER: Ratkai A 

PROVIDER: S-EPMC7864958 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature