The membrane response of hippocampal CA3b pyramidal neurons near rest: Heterogeneity of passive properties and the contribution of hyperpolarization-activated currents

Abstract

Pyramidal neurons in the CA3 region of the hippocampal formation integrate synaptic information arriving in the dendrites within discrete laminar regions. At potentials near or below the resting potential integration of synaptic signals is most affected by the passive properties of the cell and hyperpolarization-activated currents (Ih). Here we focused specifically on a subset of neurons within the CA3b subregion in order to better understand their membrane response within subthreshold voltage ranges. Using a combined experimental and computational approach we found that the passive properties of these neurons varied up to 5-fold between cells. Likewise, there was a large variance in the expression of Ih channels. However, the contribution of Ih was minimal at resting potentials endowing the membrane with an apparent linear response to somatic current injection within ±10 mV. Unlike in CA1 pyramidal neurons, however, Ih activation was not potentiated in an activity dependent-manner. Computer modeling, based on a combination of voltage- and current-clamp data, suggested that an increasing density of these channels with distance from the soma, compared with a uniform distribution, would have no significant effect on the general properties of the cell because of their relatively lower expression. Nonetheless, temporal summation of excitatory inputs was affected by the presence of Ih in the dendrites in a frequency- and distance-dependent fashion.

Properties and functional implications of I h in hippocampal area CA3 interneurons

“…This effect of I h was shown previously in computational simulations and experiments in which h-conductance was low [32,44,77,87]. These results suggest that, even though I h does not confer theta resonance to R/L-M interneurons, I h attenuates the frequency dependence of response amplitude.…”

“…The impedance properties have been thoroughly documented for CA1 interneurons [95]. However, while the properties and implications of I h for temporal summation and impedance have been examined for CA3 pyramidal cells [32], complementary studies are not available for CA3 interneurons. It is known that I h supports sensitivity to input timing in CA3 R/L-M interneurons based on pharmacological manipulations [11], but the biophysical properties of I h and the effects of this current on responses to in vivo-like input have not been studied.…”

Network bursting using experimentally constrained single compartment CA3 hippocampal neuron models with adaptation

“…Using this value and the input resistance R n = 167 M gives a membrane time constant τ m = R n C ≈ 41.75 ms, which is well within the range of values observed by Hemond et al (2009): 15-139 ms.…”

“…Recently, simple models of spiking neurons (with some minimal biophysical character) have been shown to capture a wide range of cellular firing characteristics (Izhikevich 2003(Izhikevich , 2007. Using this formulation, we develop an intrinsic model of a CA3 excitatory cell that has direct links with experimental data regarding spike frequency adaptation characteristics (Hemond et al 2008(Hemond et al , 2009Migliore et al 2010). We show that network bursting occurs robustly with large networks of these CA3 models and explain the underlying bursting mechanism using two-cell models and phase plane analyses.…”

Excitability governs neural development in a hippocampal region specific manner

“…CA3 and CA1 pyramidal neurons even share similar morphology and ontogeny (Bayer, 1980a,b). Nonetheless, there are also distinct differences between these cell populations, particularly those related to intrinsic excitability, including membrane properties, HCN channel expression and firing rate (Spigelman et al, 1992;Santoro et al, 2000;Tyzio et al, 2003;Spruston and McBain, 2006;Hemond et al, 2009;Nowacki et al, 2011). Perhaps because of these differences in intrinsic excitability, these neurons also display unique forms of synaptic plasticity (Lynch, 2004) and have different disease susceptibility (Mathern et al, 1995;Borges et al, 2003;Fujita et al, 2014).…”