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 (CaV3) 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 CaV3 channels, respectively. All HCN subunits (HCN1 to 4) and T-type Ca-channel subunits (CaV3.1, 3.2 and 3.3) were expressed in both control and activity-deprived hippocampal cultures. Elevated expression levels of CaV3.1 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.
Highlights
Homeostatic plasticity stabilizes neuronal networks by adjusting the responsiveness of neurons according to their global activity and the intensity of the synaptic inputs
Our findings indicate that hyperpolarization-activated cyclic nucleotide-gated (HCN) and T-type Ca-channels actively contribute to the homeostatic regulation of intrinsic excitability and plasticity in pyramidal neurons and have important role in synchronizing network activity
The percentage of spikes emitted within bursts increased dramatically that indicates the tight synchronization of activity in the network of cultured hippocampal neurons (Fig. 1F)
Summary
Homeostatic plasticity stabilizes neuronal networks by adjusting the responsiveness of neurons according to their global activity and the intensity of the synaptic inputs. Classic forms of Hebbian plasticity, such as long-term potentiation (LTP) or depression (LTD), are some of the most investigated basic mechanisms of learning and memory formation, but their effects could destabilize the neuronal network without effective negative feedback regulation As one of such mechanisms, homeostatic plasticity balances neuronal network activity by allowing the neurons to adapt their intrinsic excitability and synaptic responses according to the intensity of the inputs they experience. Various forms of intrinsic plasticity have been shown to regulate EPSP (excitatory postsynaptic potential) amplification, voltage threshold of spike initiation, and depolarization of the resting membrane potential These effects can change intrinsic properties through alteration of specific voltage-gated channels in an activity-dependent m anner[12,13,14]. It has been suggested that intrinsic plasticity links Hebbian and homeostatic plasticity, facilitating the formation of neuronal networks that are sufficiently malleable and stable at the same t ime[12,13]
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