Enhanced intrinsic excitability and EPSP-spike coupling accompany enriched environment-induced facilitation of LTP in hippocampal CA1 pyramidal neurons

Abstract

Environmental enrichment (EE) is a well-established paradigm for studying naturally occurring changes in synaptic efficacy in the hippocampus that underlie experience-induced modulation of learning and memory in rodents. Earlier research on the effects of EE on hippocampal plasticity focused on long-term potentiation (LTP). Whereas many of these studies investigated changes in synaptic weight, little is known about potential contributions of neuronal excitability to EE-induced plasticity. Here, using whole-cell recordings in hippocampal slices, we address this gap by analyzing the impact of EE on both synaptic plasticity and intrinsic excitability of hippocampal CA1 pyramidal neurons. Consistent with earlier reports, EE increased contextual fear memory and dendritic spine density on CA1 cells. Furthermore, EE facilitated LTP at Schaffer collateral inputs to CA1 pyramidal neurons. Analysis of the underlying causes for enhanced LTP shows EE to increase the frequency but not amplitude of miniature excitatory postsynaptic currents. However, presynaptic release probability, assayed using paired-pulse ratios and use-dependent block of N-methyl-d-aspartate receptor currents, was not affected. Furthermore, CA1 neurons fired more action potentials (APs) in response to somatic depolarization, as well as during the induction of LTP. EE also reduced spiking threshold and after-hyperpolarization amplitude. Strikingly, this EE-induced increase in excitability caused the same-sized excitatory postsynaptic potential to fire more APs. Together, these findings suggest that EE may enhance the capacity for plasticity in CA1 neurons, not only by strengthening synapses but also by enhancing their efficacy to fire spikes-and the two combine to act as an effective substrate for amplifying LTP.

Environmental enrichment modulates intrinsic cellular excitability of hippocampal CA1 pyramidal cells in a housing duration and anatomical location-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]).…”

“…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.…”

“…However, studies on intrinsic cellular excitability are few and, so far, contradictory [9,22,35], leaving some important questions to be addressed.…”

Differential effects of static and dynamic inputs on neuronal excitability

“…; Malik and Chattarji 2012;Poolos et al 2002). These experiments provide several quantitative measures of the neurons' excitability such as the rheobase and gain.…”

Cellular Basis for Learning Impairment in Fragile X Syndrome

“…Other conditions in which alterations of LTP are associated with altered burst responses include suppressed LTP in transgenic mouse models for Alzheimer's disease (Larson et al, 1999), suppressed LTP by diazepam (del Cerro et al, 1992), reduced LTP after neonatal lesions of contralateral hippocampus (van Praag et al, 1998), reduced LTP after inhibition of matrix metalloproteinases (Meighan et al, 2007), enhanced LTP in mice overexpressing brain protease nexin-1 (Luthi et al, 1997), facilitated LTP by an M1 muscarinic antagonist (Boddeke et al, 1992), and enhanced LTP after environmental enrichment (Malik and Chattarji, 2012), among others. Recording and analyzing the burst response pattern can help to provide a first-pass evaluation of whether an experimental manipulation affects events before or after the NMDA receptor-mediated influx of calcium that serves as the essential trigger for LTP induction.…”