Developmental Changes in HCN Channel Modulation of Neocortical Layer 1 Interneurons
نویسندگان
چکیده
Layer 1 (L1) interneurons (INs) play a key role in modulating the integration of inputs to pyramidal neurons (PNs) and controlling cortical network activity. Hyperpolarization-activated, cyclic nucleotide-gated, non-specific cation (HCN) channels are known to alter the intrinsic and synaptic excitability of principal components (PCs) as well as select populations of GABAergic INs. However, the developmental profile and functional role of HCN channels in diverse L1 IN populations is not completely understood. In the present study, we used electrophysiological characterization, in conjunction with unbiased hierarchical cluster analysis, to examine developmental modulation of L1 INs by HCN channels in the rat medial agranular cortex (AGm). We identified three physiologically discrete IN populations which were classified as regular spiking (RS), burst accommodating (BA) and non-accommodating (NA). A distinct developmental pattern of excitability modulation by HCN channels was observed for each group. RS and NA cells displayed distinct morphologies with modulation of EPSPs increasing in RS cells and decreasing in NA cells across development. The results indicate a possible role of HCN channels in the formation and maintenance of cortical circuits through alteration of the excitability of distinct AGm L1 INs.
منابع مشابه
HCN Channel Modulation of Synaptic Integration in GABAergic Interneurons in Malformed Rat Neocortex
Cortical malformations are often associated with pharmaco-resistant epilepsy. Alterations in hyperpolarization-activated, cyclic nucleotide-gated, non-specific cation (HCN) channels have been shown to contribute to malformation associated hyperexcitability. We have recently demonstrated that expression of HCN channels and Ih current amplitudes are reduced in layer (L) 5 pyramidal neurons of rat...
متن کاملRegulation of epileptiform discharges in rat neocortex by HCN channels 1 2
25 Hyperpolarization-activated, cyclic-nucleotide gated, non-specific cation (HCN) 26 channels have a well-characterized role in regulation of cellular excitability and network 27 activity. The role of these channels in control of epileptiform discharges is less 28 thoroughly understood. This is especially pertinent given altered HCN channel 29 expression in epilepsy. We hypothesized that inhib...
متن کاملDifferential modulation of repetitive firing and synchronous network activity in neocortical interneurons by inhibition of A-type K+ channels and Ih
GABAergic interneurons provide the main source of inhibition in the neocortex and are important in regulating neocortical network activity. In the presence 4-aminopyridine (4-AP), CNQX, and D-APV, large amplitude GABAA-receptor mediated depolarizing responses were observed in the neocortex. GABAergic networks are comprised of several types of interneurons, each with its own protein expression p...
متن کاملRegulation of epileptiform discharges in rat neocortex by HCN channels.
Hyperpolarization-activated, cyclic nucleotide-gated, nonspecific cation (HCN) channels have a well-characterized role in regulation of cellular excitability and network activity. The role of these channels in control of epileptiform discharges is less thoroughly understood. This is especially pertinent given the altered HCN channel expression in epilepsy. We hypothesized that inhibition of HCN...
متن کاملActivity-dependent modulation of layer 1 inhibitory neocortical circuits by acetylcholine.
Layer 1 neocortical GABAergic interneurons control the excitability of pyramidal neurons through cell-class-specific direct inhibitory and disynaptic disinhibitory circuitry. The engagement of layer 1 inhibitory circuits during behavior is powerfully controlled by the cholinergic neuromodulatory system. Here we report that acetylcholine (ACh) influences the excitability of layer 1 interneurons ...
متن کامل