TABLE 2.
1 | We assume that after all the listed correction in this paper, all parameters coming from different sources can be used together to parameterize the synapse models. |
2 | When using data from Kohus et al. (2016), we assumed that CCK+ DTIs (dendrite‐targeting interneurons) are SCA cells in SR. Furthermore, we assumed that synaptic currents measured in mouse CA3 are representative of similar pathways in rat CA1. |
3 | In the lack of representative data and our lack of neurogliaform cells, we assumed that all inhibitory synapses are mediated purely by GABAA receptors. |
4 | For calculating release probabilities at different [Ca2+]o, we assumed that Hill functions parameterized with cortical data generalize well for hippocampal connections. |
5 |
For modeling synaptic currents, we assumed that all CA1 synapses can be described with biexponential conductances, with vesicle release kinetics governed by the stochastic TM model. When modeling dendritic PSC decays, we assumed a single exponential function, parametrized with a time constant extracted from somatic recording. |
6 | In the process of calibrating synaptic peak conductances, we simulated only the synapses mediating the given connection and thus we assume that the background activity does not matter. |
7 | Some of the biggest assumptions are inherited from the network model: In this work, we assumed that the published electrical models of single cells (Migliore et al., 2018) capture the behavior of different neurons in rat CA1. (The fact that unlike experimentalists, we cannot clamp PC models to potentials above −58 mV without blocking sodium channels seems to violate this assumption.) We also assumed that the cell composition and cell density within each layer are homogeneous and the constrained connectivity reflects the connectivity of rat CA1. |
8 | Kinetic parameters for a given pathway are drawn from a distribution, but since (almost) all experimental data used to derive these parameters are representative for a given connection and not for individual synapses per se, we use the same parameters for all synapses mediating a single connection. |
9 |
The biggest assumption is that one can extrapolate parameters from experimentally characterized pathways, to fill in missing values. When generalizing our parameters for similar, experimentally uncharacterized pathways we group CA1 interneurons based on only one chemical marker. However, cells express many of these and the markers overlap (see hippocampome.org (Wheeler et al., 2015)). By PV+ cells we mean: SP_PVBCs, SP_BS cells, and SP_AA cells. By CCK+ cells we mean: SP_CCKBCs, SR_SCA cells and SLM_PPA cells. The only interneurons in our NOS+ class are SP_Ivy cells. (Neurogliaform cells would belong here as well.) We assume all neurons in SO: SO_OLM cells, SO_BS cells, SO_Tri cells, and SO_BP cells to be SOM+. |
10 |
A usually unspoken, implicit assumption on communication between neurons is used here as well, namely, we model only glutamatergic and GABAergic synapses between presynaptic axons and postsynaptic somata and dendrites. Thus, we leave out cotransmission and neuromodulators acting on different receptors, retrograde messengers, any kind of gap junctions and any axonal receptors. |