Elsevier

Neuroscience

Volume 160, Issue 2, 5 May 2009, Pages 359-370
Neuroscience

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

https://doi.org/10.1016/j.neuroscience.2009.01.082Get rights and content

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 of the rat hippocampus 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 fivefold 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.

Section snippets

Hippocampal slices

Animal use was in accordance with the University of Texas at San Antonio University Institutional Animal Care and Use Committee, conformed to the National Institutes of Health Guide for the Care and Use of Laboratory Animals, and every effort was made to limit the number of animals used and their suffering. Sprague–Dawley rats (Harlan Sprague-Dawley, Chicago, IL, USA) 4–6 weeks old were anesthetized with halothane followed by pentobarbital (130 mg/kg i.p.). Animals were perfused with an

Near-rest hyperpolarizing response

The typical voltage-response of CA3b pyramidal neurons to hyperpolarizing and depolarizing current steps was exponential charging of the membrane for transients that remained within 10 mV of Vrest (Fig. 1A). At more hyperpolarized potentials, a prominent sag, indicative of the activation of Ih channels was observed in most cells. Bath application of cesium (5 mM) or ZD7288 (30 μM) blocked the sag and linearized the voltage–current response (Fig. 1B). The cesium- and ZD7288-sensitive component

Discussion

The primary finding of this study is that for pyramidal neurons in area CA3b the passive properties and Ih are expressed heterogeneously among cells. Additionally, since the activation of Ih occurs at potentials well below Vrest, little Ih conductance is active at rest. Moreover, its density is relatively low (a comparison with CA1 pyramidal cells is discussed below) and it is not enhanced in an activity-dependent manner, raising the possibility that it plays little role in dendritic synaptic

Acknowledgments

This work was supported by CRCNS grant AG25633. We also thank the CINECA Consortium (Bologna, Italy) for granting access to their parallel supercomputer systems.

References (47)

  • A. Agmon et al.

    The role of the hyperpolarization-activated cationic current I(h) in the timing of interictal bursts in the neonatal hippocampus

    J Neurosci

    (2003)
  • G.A. Ascoli

    Mobilizing the base of neuroscience data: the case of neuronal morphologies

    Nat Rev Neurosci

    (2006)
  • C.G. Assisi et al.

    Synchrony and clustering in heterogeneous networks with global coupling and parameter dispersion

    Phys Rev Lett

    (2005)
  • R.A. Bender et al.

    Synchronized network activity in developing rat hippocampus involves regional hyperpolarization-activated cyclic nucleotide-gated (HCN) channel function

    Eur J Neurosci

    (2005)
  • B.H. Bland et al.

    Heterogeneity among hippocampal pyramidal neurons revealed by their relation to theta-band oscillation and synchrony

    Exp Neurol

    (2005)
  • D.H. Brager et al.

    Plasticity of intrinsic excitability during long-term depression is mediated through mGluR-dependent changes in I(h) in hippocampal CA1 pyramidal neurons

    J Neurosci

    (2007)
  • E. Campanac et al.

    Spike timing-dependent plasticity: a learning rule for dendritic integration in rat CA1 pyramidal neurons

    J Physiol

    (2008)
  • M.I. Chelaru et al.

    Efficient coding in heterogeneous neuronal populations

    Proc Natl Acad Sci U S A

    (2008)
  • A. Destexhe et al.

    Impact of network activity on the integrative properties of neocortical pyramidal neurons in vivo

    J Neurophysiol

    (1999)
  • Y. Fan et al.

    Activity-dependent decrease of excitability in rat hippocampal neurons through increases in I(h)

    Nat Neurosci

    (2005)
  • A. Fisahn et al.

    Muscarinic induction of hippocampal gamma oscillations requires coupling of the M1 receptor to two mixed cation currents

    Neuron

    (2002)
  • M. Hausser et al.

    Dendrites: bug or feature?

    Curr Opin Neurobiol

    (2003)
  • P. Hemond et al.

    Distinct classes of pyramidal cells exhibit mutually exclusive firing patterns in hippocampal area CA3b

    Hippocampus

    (2008)
  • M.L. Hines et al.

    The NEURON simulation environment

    Neural Comput

    (1997)
  • H. Hu et al.

    Two forms of electrical resonance at theta frequencies, generated by M-current, h-current and persistent Na+ current in rat hippocampal pyramidal cells

    J Physiol

    (2002)
  • D.B. Jaffe et al.

    Passive normalization of synaptic integration influenced by dendritic architecture

    J Neurophysiol

    (1999)
  • D. Johnston et al.

    Active dendrites: colorful wings of the mysterious butterflies

    Trends Neurosci

    (2008)
  • J.L. Krichmar et al.

    Effects of dendritic morphology on CA3 pyramidal cell electrophysiology: a simulation study

    Brain Res

    (2002)
  • A. Lorincz et al.

    Polarized and compartment-dependent distribution of HCN1 in pyramidal cell dendrites

    Nat Neurosci

    (2002)
  • G. Maccaferri et al.

    The hyperpolarization-activated current (Ih) and its contribution to pacemaker activity in rat CA1 hippocampal stratum oriens-alveus interneurones

    J Physiol

    (1996)
  • J.C. Magee

    Dendritic hyperpolarization-activated currents modify the integrative properties of hippocampal CA1 pyramidal neurons

    J Neurosci

    (1998)
  • J.C. Magee

    Dendritic lh normalizes temporal summation in hippocampal CA1 neurons

    Nat Neurosci

    (1999)
  • G. Major et al.

    Detailed passive cable models of whole-cell recorded CA3 pyramidal neurons in rat hippocampal slices

    J Neurosci

    (1994)

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