Elsevier

Neuroscience

Volume 157, Issue 3, 2 December 2008, Pages 495-501
Neuroscience

Rapid Report
A possible role of ectopic action potentials in the in vitro hippocampal sharp wave–ripple complexes

https://doi.org/10.1016/j.neuroscience.2008.09.040Get rights and content

Abstract

Sharp wave–ripple (SPW-R) complexes are physiological pattern of network activity in the hippocampus thought to play important role in memory consolidation. During SPW-R activity the excitability of both pyramidal cells and certain types of interneurons in the CA1 region is transiently increased. As a result pyramidal cells receive inhibitory input during network oscillation, yet a relatively small group of pyramidal cells transmit their output to CA1 targets. However, the exact nature of CA1 output during SPW-R activity is not clear. In this study, using simultaneous intracellular and field recordings from rat ventral hippocampal slices maintained at 32 °C and spontaneously generating SPW-R complexes we show that 20% of CA1 pyramidal cells fired putative ectopic action potentials (e-APs) phase-related to SPW-Rs. The highest probability of ectopic discharge occurred at the maximal amplitude of the ripple oscillation and always during the period of SPW-R-associated inhibitory postsynaptic potentials (IPSPs) in pyramidal cells. Both e-APs and IPSPs were abolished under blockade of GABAA receptor-mediated synaptic transmission by bicuculline. Ectopic APs phase-locked to SPW-R events were also evoked by Schaffer collateral stimulation subthreshold for and with longer latency than monosynaptic orthodromic APs. A fraction of CA1 pyramidal cells (25.7%), most of them distinct from the cells firing e-APs, fired orthodromic APs with highest probability before the onset of SPW-Rs. We hypothesize that putative ectopic spikes in pyramidal cells, presumably triggered by GABAergic synaptic mechanisms, by serving as output of the CA1 region might provide a reliable mechanism for optimized information transfer between hippocampus and its cortical targets during SPW-R activity. On the other hand, orthodromic APs might contribute to the initiation and synchronization of the population activity.

Section snippets

Slice preparation

Hippocampal slices were prepared from 17 young adult (4–6 weeks old) male Wistar rats. All measures were taken to minimize animal suffering and to reduce the number of the animals used, according to the European Communities Council Directive Guidelines (86/609/EEC) for the care and use of laboratory animals. Furthermore, animal treatment was approved by the local ethics committee. Animals were deeply anesthetized with diethyl-ether, were decapitated and the brains were removed and placed in

Results

Intracellular recordings from 35 neurons and simultaneous extracellular recordings were made from the stratum pyramidale of the CA1b field. All recorded cells were situated at least 150 μm deep from the surface of the slices and were putative principal neurons as concluded on the basis of their accommodating firing mode in response to depolarizing DC current injection (300–500 ms, 0.1–0.5 nA), their resting membrane potential (−62.35±0.98 mV) and input resistance (54.5±4.2 MΩ). In line with

Discussion

The present findings show that two relatively distinct populations of CA1 pyramidal cells fire at different temporal windows with respect to SPW-R activity. Furthermore, firing in the two populations is apparently triggered by distinct mechanisms. In one subset of pyramidal cells depolarization-induced o-APs most frequently occur before the onset of SPW-Rs while the cells in a second group fire maximally during the peaking phase of the ripple oscillation coinciding with the hyperpolarization of

Acknowledgments

This study was supported by a “Karatheodori” grant (# C 176) of the Research Committee of the University of Patras. The author thanks Dr. G. Kostopoulos as well as Dr. P. Giannopoulos, E. Koniaris and D. Kotzadimitriou for valuable discussions.

References (46)

  • M. Takeya et al.

    Contribution of nitric oxide to the depression of neuronal activity induced by temperature increase in the rat hippocampal CA1 area

    Neurosci Lett

    (2003)
  • C.H. Vanderwolf

    Hippocampal electrical activity and voluntary movement in the rat

    Electroencephalogr Clin Neurophysiol

    (1969)
  • M. Avoli et al.

    GABA-dependent generation of ectopic action potentials in the rat hippocampus

    Eur J Neurosci

    (1998)
  • E.H. Buhl et al.

    Physiological properties of anatomically identified axo-axonic cells in the rat hippocampus

    J Neurophysiol

    (1994)
  • G. Buzsaki

    The hippocampo-neocortical dialogue

    Cereb Cortex

    (1996)
  • G. Buzsaki et al.

    High-frequency network oscillation in the hippocampus

    Science

    (1992)
  • J.J. Chrobak et al.

    Selective activation of deep layer (V-VI) retrohippocampal cortical neurons during hippocampal sharp waves in the behaving rat

    J Neurosci

    (1994)
  • J.J. Chrobak et al.

    High-frequency oscillations in the output networks of the hippocampal-entorhinal axis of the freely behaving rat

    J Neurosci

    (1996)
  • J.J. Chrobak et al.

    Gamma and ripple oscillations: functional indices of hippocampal-entorhinal interactions

  • S.R. Cobb et al.

    Synchronization of neuronal activity in hippocampus by individual GABAergic interneurons

    Nature

    (1995)
  • J. Csicsvari et al.

    Oscillatory coupling of hippocampal pyramidal cells and interneurons in the behaving rat

    J Neurosci

    (1999)
  • M.J. Gutnick et al.

    Thalamocortical relay neurons: antidromic invasion of spikes from a cortical epileptogenic focus

    Science

    (1972)
  • E.R. Kandel et al.

    Electrophysiology of hippocampal neuronsI. Sequential invasion and synaptic organization

    J Neurophysiol

    (1961)
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