Simple models of quantitative firing phenotypes in hippocampal neurons: Comprehensive coverage of intrinsic diversity

Abstract

Patterns of periodic voltage spikes elicited by a neuron help define its dynamical identity. Experimentally recorded spike trains from various neurons show qualitatively distinguishable features such as delayed spiking, spiking with or without frequency adaptation, and intrinsic bursting. Moreover, the input-dependent responses of a neuron not only show different quantitative features, such as higher spike frequency for a stronger input current injection, but can also exhibit qualitatively different responses, such as spiking and bursting under different input conditions, thus forming a complex phenotype of responses. In previous work, the comprehensive knowledge base of hippocampal neuron types Hippocampome.org systematically characterized various spike pattern phenotypes experimentally identified from 120 neuron types/subtypes. In this paper, we present a complete set of simple phenomenological models that quantitatively reproduce the diverse and complex phenotypes of hippocampal neurons. In addition to point-neuron models, we created compact multi-compartment models with up to four compartments, which will allow spatial segregation of synaptic integration in network simulations. Electrotonic compartmentalization observed in our compact multi-compartment models is qualitatively consistent with experimental observations. The models were created using an automated pipeline based on evolutionary algorithms. This work maps 120 neuron types/subtypes in the rodent hippocampus to a low-dimensional model space and adds another dimension to the knowledge accumulated in Hippocampome.org. Computationally efficient representations of intrinsic dynamics, along with other pieces of knowledge available in Hippocampome.org, provide a biologically realistic platform to explore the large-scale interactions of various neuron types at the mesoscopic level.

Chronic stress differentially altersmRNAexpression of opioid peptides and receptors in the dorsal hippocampus of female and male rats

“…Additionally, the presence of dark and light PENK granule cells may reflect the existence of different subsets of PENK granule cells. This idea would be consistent with recent demonstration of diverse molecular markers in granule cells (Hamilton et al, 2017; Venkadesh et al, 2019). The significance of this observation in light of sex differences in the expression of PENK in granule cells is a topic of future investigations.…”

Itinerant complexity in networks of intrinsically bursting neurons

“…It was previously reported that bursting dynamics do not exist for low values of the parameter in the IM neuron (see eqn-1) [24]. We obtained doublet-and singlet-spiking neuron models by only varying parameter from the chaotic-spiking model ( =1.5; =175pA and =0.5; =200pA for doublet-and singlet-spiking neurons respectively) (Fig 3).…”

An update to Hippocampome.org by integrating single-cell phenotypes with circuit function in vivo

“…We noticed that existing Hippocampome.org information on membrane biophysics and firing patterns were all obtained in vitro from slice preparations. Given their relevance to inform computational models [ 30 ], we favor sharp intracellular recordings in vivo to complement these in vitro data. Thus, we obtained new data from cells in the DG ( n = 3 granule cells and a mossy cell) and CA3 region ( n = 7), as well as from GABAergic cells ( n = 2 PV basket cells).…”