Adaptive spike threshold dynamics associated with sparse spiking of hilar mossy cells are captured by a simple model

Trinh, Anh-Tuan ✉; Girardi-Schappo, Mauricio ✉; Beique, Jean-Claude; Longtin, Andre; Maler, Leonard

Angol nyelvű Szakcikk (Folyóiratcikk) Tudományos
Megjelent: JOURNAL OF PHYSIOLOGY-LONDON 0022-3751 1469-7793 601 (19) pp. 4397-4422 2023
  • SJR Scopus - Physiology: D1
Azonosítók
Szakterületek:
  • Általános orvostudomány
  • Biológiai tudományok
Hilar mossy cells (hMCs) in the dentate gyrus (DG) receive inputs from DG granule cells (GCs), CA3 pyramidal cells and inhibitory interneurons, and provide feedback input to GCs. Behavioural and in vivo recording experiments implicate hMCs in pattern separation, navigation and spatial learning. Our experiments link hMC intrinsic excitability to their synaptically evoked in vivo spiking outputs. We performed electrophysiological recordings from DG neurons and found that hMCs displayed an adaptative spike threshold that increased both in proportion to the intensity of injected currents, and in response to spiking itself, returning to baseline over a long time scale, thereby instantaneously limiting their firing rate responses. The hMC activity is additionally limited by a prominent medium after-hyperpolarizing potential (AHP) generated by small conductance K+ channels. We hypothesize that these intrinsic hMC properties are responsible for their low in vivo firing rates. Our findings extend previous studies that compare hMCs, CA3 pyramidal cells and hilar inhibitory cells and provide novel quantitative data that contrast the intrinsic properties of these cell types. We developed a phenomenological exponential integrate-and-firemodel that closely reproduces the hMC adaptive threshold nonlinearities with respect to their threshold dependence on input current intensity, evoked spike latency and long-lasting spike-induced increase in spike threshold. Our robust and computationally efficient model is amenable to incorporation into large network models of the DG that will deepen our understanding of the neural bases of pattern separation, spatial navigation and learning.Abstract figure legend In the hilar network, a micro-circuit in the dentate gyrus (DG), the hilar mossy cells (hMCs) are the main excitatory feedback input to DG. Although the hMCs exhibit sparse spiking in vivo, it is not known whether this is a consequence of their intrinsic biophysics or the hilar inhibitory interneurons. To test the contribution of hMC intrinsic properties, we performed whole-cell patch recordings of the hMCs and other main cell types in the mouse hilar network. All tested neurons exhibited an increase in the threshold voltage following successive spiking and their spike threshold was dependent on the stimulus intensity - a new finding. Further, only the CA3 and hMC exhibited a slow adaptation lasting over hundreds of milliseconds to this increase in spike threshold. We developed a new integrate-and-fire-like model that captured the threshold dynamics of hMCs. This might pave the way for future network simulations, shedding light on memory dynamics. Created with BioRender.com.
Hivatkozás stílusok: IEEEACMAPAChicagoHarvardCSLMásolásNyomtatás
2025-11-13 17:59