Abstract
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.
Highlights
In mature neocortex, a small population of GABAergic cells comprises the entirety of layer 1 (L1) neurons (DeFelipe and Jones, 1988; Winer and Larue, 1989; Hestrin and Armstrong, 1996; Zhou and Hablitz, 1996b)
When the correlation of individual cells was plotted on the same axes (Figure 1B, right) initial firing frequency and frequency adaptation most strongly identify Group 3, with Groups 1 and 2 being distributed along the same principal components (PCs) axis
To characterize the contribution of HCN channels to the synaptic excitability of Layer 1 (L1) INs, we evaluated the effect of ZD7288 application on the integration of synaptic responses evoked at 10, 20 and 40 Hz (Figure 4)
Summary
A small population of GABAergic cells comprises the entirety of layer 1 (L1) neurons (DeFelipe and Jones, 1988; Winer and Larue, 1989; Hestrin and Armstrong, 1996; Zhou and Hablitz, 1996b). Given L1’s critical role in establishing cortical lamination and circuitry, the functional impact of hyperpolarization-activated, cyclic nucleotide-gated, non-specific cation (HCN) channels on L1 INs during development is potentially important. Identification of mechanisms which regulate the intrinsic and synaptic excitability of L1 neurons is pivotal to understand the network dynamics underlying information processing. Identifying the role of HCN channels in modulating excitability and synaptic integration in L1 INs will increase our understanding of the basic mechanisms governing cortical network activity which underlies information processing. To this end, we used whole-cell electrophysiological recordings to determine the extent to which HCN channels affect the intrinsic and synaptic excitability of AGm L1 INs throughout development. We have identified physiologically discrete subsets of L1 INs with distinct developmental patterns of modulation by HCN channels
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
