Research reportEnvironmental enrichment modulates intrinsic cellular excitability of hippocampal CA1 pyramidal cells in a housing duration and anatomical location-dependent manner
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)
- et al.
Duration of environmental enrichment influences the magnitude and persistence of its behavioral effects on mice
Physiol. Beahv.
(2008) - et al.
Learning, aging and intrinsic neuronal plasticity
Trends Neurosci.
(2006) - et al.
Increased expression of brain-derived neurotrophic factor mRNA in rat is associated with improved spatial memory and enriched environment
Neurosci. Lett.
(1992) - et al.
Are the dorsal and ventral hippocampus functionally distinct structures?
Neuron
(2010) - et al.
Environmental enrichment in female rodents: considerations in the effects on behavior and biochemical markers
Behav. Brain Res.
(2013) - et al.
Impact of enriched-environment housing on brain-derived neurotrophic factor and on cognitive performance after a transient global ischemia
Behav. Brain Res.
(2004) - et al.
Spatial representation along the proximodistal axis of CA1
Neuron
(2010) - et al.
Transformation of cortical and hippocampal neural circuit by environmental enrichment
Neuroscience
(2014) - et al.
Long-term environmental enrichment leads to regional increases in neurotrophin levels in the ral brain
Exp. Neurol.
(2000) - et al.
Environmental enrichment decreases the afterhyperpolarization in senescent rats
Brain Res.
(2007)
Environmental enrichment promotes improved spatial abilities and enhanced dendritic growth in the rat
Behav. Brain Res.
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.
The impact of environmental enrichment in laboratory rats – behavioural and neurochemical aspects
Behav. Brain Res.
Multiple pharmacological actions of centrally acting antitussives – do they target G protein-coupled inwardly rectifying K+ (GIRK) channels?
J. Pharmacol. Sci.
Differencial environmental regulation of neurogenesis along the septo-temporal axis of the hippocampus
Neuropharmacology
The effects of brain-derived neurotrophic factor (BDNF) administration on kindling induction, Trk expression and seizure-related morphological changes
Neuroscience
Influence of environmental manipulation on exploratory behaviour in male BDNF knockedout mice
Behav. Brain Res.
Metaplasticity: tuning synapses and networks for plasticity
Nat. Rev. Neurosci.
Activation of protein kinase C increases neuronal excitability by regulating persistent Na+ current in mouse neocortical slices
J. Neurophysiol.
Run-down of the Ca current during long whole-cell recordings in guinea pig heart cells: role of phosphorylation and intracellular calcium
Pflugers Arch.
Environmental enrichment in mice decreases anxiety, attenuates stress responses and enhances natural killer cell activity
Eur. J. Neurosci.
The influence of objects on place field expression and size hippoampal CA1
Hippocampus
Long-term plasticity of intrinsic excitability: learning rules and mechanisms
Learn. Mem.
Environmental enrichment modifies the PKA-dependence of hippocampal LTP and improves hippocampus-dependent memory
Learn. Mem.
Effects of environmental enrichment exposure on synaptic transmission and plasticity in the hippocampus
Curr. Top Behav. Neurosci.
Cited by (13)
Androgen Affects the Dynamics of Intrinsic Plasticity of Pyramidal Neurons in the CA1 Hippocampal Subfield in Adolescent Male Rats
2020, NeuroscienceCitation Excerpt :Long term potentiation, long term depression and depotentiation in the hippocampal CA1 region are also affected by androgen (Harley et al., 2000; Pettorossi et al., 2013). In addition to synaptic plasticity, the intrinsic plasticity of CA1 neurons can also play an important role in modulating hippocampal functions (Hirase and Shinohara, 2014; Valero-Aracama et al., 2015). To date, there is very scant relevant information concerning AR distribution in the hippocampus and the underlying effects of androgen on intrinsic plasticity.
Plasticity of intrinsic neuronal excitability
2019, Current Opinion in NeurobiologyCitation Excerpt :Regulations of neuronal excitability have been involved in others forms of learning such as spatial learning [18], fear conditioning [19–22], odor discrimination [23–25]. Experiencing new or enriched environment is also known to affect intrinsic excitability [26,27]. Following learning, usually after-hyperpolarization (AHP), AP threshold and accommodation are decreased resulting in an enhancement of AP firing and neuronal IE in the hippocampus (spatial and fear conditioning), amygdala (fear conditioning and odor discrimination), or prefrontal cortex (fear conditioning).
Dorsal–Ventral Gradient of Activin Regulates Strength of GABAergic Inhibition along Longitudinal Axis of Mouse Hippocampus in an Activity-Dependent Fashion
2023, International Journal of Molecular Sciences