Elsevier

Behavioural Brain Research

Volume 292, 1 October 2015, Pages 209-218
Behavioural Brain Research

Research report
Environmental enrichment modulates intrinsic cellular excitability of hippocampal CA1 pyramidal cells in a housing duration and anatomical location-dependent manner

https://doi.org/10.1016/j.bbr.2015.05.032Get rights and content

Highlights

  • Environmental enrichment increased intrinsic excitability of hippocampal CA1 cells.

  • Only a short (<40 days) environmental enrichment increased the excitability.

  • This increased excitability was specific to dorsal and proximal hippocampal cells.

  • Input resistance and spike threshold underlay these modulations.

Abstract

Housing animals in enriched environments (EEs) results in improved learning and memory (L&M) performance. While increased intrinsic cellular excitability in the hippocampal neurons might underlie the environmental enrichment-dependent L&M enhancement, literature in respect to this remains scarce and controversial. In this study, we explore whether intrinsic cellular excitability in hippocampal CA1 pyramidal cells is modulated differently, depending on housing duration and anatomical location of cells. Using in vitro patch clamp recordings in mice, we first demonstrate that cellular excitability of hippocampal CA1 pyramidal cells is significantly increased only in animals housed in an EE for a relatively short (<40 days) duration. Second, anatomical analysis shows that increased excitability is mainly restricted to the dorsal and proximal sections of the CA1 region. Further analysis reveals that the input resistance and the spike threshold, which are differently modulated by anatomical location and housing duration, respectively, may underlie the increased excitability. These results indicate that housing duration and anatomical location are crucial factors for environmental enrichment-dependent modulations of intrinsic excitability. While the dorsally restricted increase in excitability is in agreement with the specific up-regulation of L&M supported by the dorsal hippocampus, the selective modulation of the proximal area is in line with enhanced spatial abilities often observed after environmental enrichment. The housing duration specificity we observed here, together with previous findings, suggests that the modulation of some physiological properties by an environmental enrichment is transient. Finally, these results could coherently account for earlier controversial reports.

Introduction

Over the last 50 years, environmental enrichment has been shown to exert many beneficial effects, including an enhancement of hippocampal-dependent learning and memory (L&M) tasks, such as spatial navigation and object recognition [32], [41]. Multiple modulations of cellular and synaptic properties by environmental enrichment could support hippocampal-dependent L&M: increased spine density [18], [41], increased neurogenesis [26], increased concentration of neurotrophic factors [12], [23], and facilitation of synaptic plasticity [9], [20]. In addition, an up-regulation of intrinsic cellular excitability in CA1 pyramidal cells due to environmental enrichment has recently been observed [35]. Since increased intrinsic excitability of CA1 pyramidal cells accompanies successful L&M [1], intrinsic excitability might play an important role in enhanced L&M by environmental enrichment. However, studies on intrinsic cellular excitability are few and, so far, contradictory [9], [22], [35], leaving some important questions to be addressed.

First, it remains unclear whether intrinsic excitability in CA1 pyramidal cells is modulated in a housing duration-dependent manner. While increased intrinsic excitability was observed after a relatively short duration of enrichment (<35 days; [35]), this was not the case in another study which used a longer duration (8 weeks; [9]). Interestingly, it has recently been pointed out in a review article, that enhanced synaptic properties and population spike induction by environmental enrichment, were mostly observed in studies with a relatively short housing duration (<4 weeks; [10]). However, a systematic study of the effect of housing duration on intrinsic cellular excitability has not been reported. Second, it is unknown whether environmental enrichment modulates intrinsic cellular excitability in an anatomical location-dependent manner within the CA1 area. It has been suggested that different hippocampal anatomical sub-regions support distinct functions; while the dorsal hippocampus is engaged in L&M, the ventral hippocampus mediates fear expression [28], [36]. Environmental enrichment might have a predominant effect on the dorsal area, effectively enhancing L&M. In fact, environmental enrichment-dependent increments in neurogenesis are larger in the dorsal than in the ventral dentate gyrus [46]. It has also been suggested that proximal CA1 supports spatial memory [21], while distal CA1 supports non-spatial memory [6]. However, so far it remains unclear whether or not environmental enrichment-dependent modulation of intrinsic excitability is anatomical location-dependent.

Based on this, we conducted in vitro whole-cell recordings from CA1 pyramidal cells in mice, housed either in an enriched environment (EE) or in a control environment (CE). Our results suggest that intrinsic cellular excitability of CA1 pyramidal cells is modulated both in a housing duration and in an anatomical location-dependent manner.

Section snippets

Animals and housing

All experimental protocols were approved by the local ethic committee (Der Tierschutzbeauftragte, Ruhr-Univeristät Bochum), and experiments were carried out in accordance with the European Communities Council Directive of September 22nd, 2010 (2010/63/EU). 72 C57BL/6 female mice (bred from Charles River parent stock) were taken at weaning age (postnatal days 21–25, depending on their size) and randomly assigned to two housing conditions. In the EE, groups of 3–9 mice (the number of female mice

Environmental enrichment increases intrinsic excitability in a housing duration dependent manner

Previous studies reported both an increased [35] and a similar [9] intrinsic excitability of CA1 pyramidal cells after an exposure to an EE. To test whether the exposure of the mice to the EE increased the excitability of CA1 pyramidal cells in our experiment, we first compared the amount of current needed to trigger at least one spike (minimum current: MC), using the IV protocol (see methods; Fig. 2A). The cells from animals housed in the EE (EE cells) started spiking with significantly

Discussion

In this study we compared intrinsic cellular properties of CA1 pyramidal cells from animals housed in a CE or an EE. We measured intrinsic cellular excitability, which is a possible mechanism underlying enhanced L&M performance in animals housed in an EE [35]. The measures of MC and the number of spikes triggered by current injections indicated that EE cells were more excitable than CE cells. When cells were categorized into sub-groups, based on housing duration and anatomical locations, a

Conclusion

In this study we observed a modulation of intrinsic cellular excitability in CA1 pyramidal cells due to environmental enrichment. Our data suggested that increased intrinsic excitability occurs in a temporally limited and anatomically specific manner. This data may provide a cohesive understanding of previously reported contradicting data regarding intrinsic excitability [9], [35], and is in agreement with the specific up-regulation of L&M supported by the dorsal hippocampus [36]. However, the

Conflict of interest

The authors declare that there are no conflicts of interest.

Acknowledgments

The authors thank S. Alexandrow for assistance with the experiments and B. Knauer for enriching scientific discussions. This work was supported by the Mercator Stiftung and the German Research Foundation (DFG) project YO177/4-1.

References (50)

  • M.G. Leggio et al.

    Environmental enrichment promotes improved spatial abilities and enhanced dendritic growth in the rat

    Behav. Brain Res.

    (2005)
  • R. Paylor et al.

    Brief exposure to an enriched environment improves performance on the Morris water task and increases hippocampal cytosolic protein kinase C activity in young rats

    Behav. Brain Res.

    (1992)
  • J. Simpson et al.

    The impact of environmental enrichment in laboratory rats – behavioural and neurochemical aspects

    Behav. Brain Res.

    (2011)
  • K. Takahama

    Multiple pharmacological actions of centrally acting antitussives – do they target G protein-coupled inwardly rectifying K+ (GIRK) channels?

    J. Pharmacol. Sci.

    (2012)
  • A. Tanti et al.

    Differencial environmental regulation of neurogenesis along the septo-temporal axis of the hippocampus

    Neuropharmacology

    (2012)
  • B. Xu et al.

    The effects of brain-derived neurotrophic factor (BDNF) administration on kindling induction, Trk expression and seizure-related morphological changes

    Neuroscience

    (2004)
  • S.W. Zhu et al.

    Influence of environmental manipulation on exploratory behaviour in male BDNF knockedout mice

    Behav. Brain Res.

    (2009)
  • W.C. Abraham

    Metaplasticity: tuning synapses and networks for plasticity

    Nat. Rev. Neurosci.

    (2008)
  • N. Astman et al.

    Activation of protein kinase C increases neuronal excitability by regulating persistent Na+ current in mouse neocortical slices

    J. Neurophysiol.

    (1998)
  • B. Belles et al.

    Run-down of the Ca current during long whole-cell recordings in guinea pig heart cells: role of phosphorylation and intracellular calcium

    Pflugers Arch.

    (1988)
  • N. Benaroya-Milshtein et al.

    Environmental enrichment in mice decreases anxiety, attenuates stress responses and enhances natural killer cell activity

    Eur. J. Neurosci.

    (2004)
  • S.N. Burke et al.

    The influence of objects on place field expression and size hippoampal CA1

    Hippocampus

    (2011)
  • G. Daoudal et al.

    Long-term plasticity of intrinsic excitability: learning rules and mechanisms

    Learn. Mem.

    (2003)
  • S.N. Duffy et al.

    Environmental enrichment modifies the PKA-dependence of hippocampal LTP and improves hippocampus-dependent memory

    Learn. Mem.

    (2001)
  • M.J. Eckert et al.

    Effects of environmental enrichment exposure on synaptic transmission and plasticity in the hippocampus

    Curr. Top Behav. Neurosci.

    (2013)
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