Hippocampal Testosterone Relates to Reference Memory Performance and Synaptic Plasticity in Male Rats

Kristina Schulz,Volker Korz

doi:10.3389/fnbeh.2010.00187

Abstract

Steroids are important neuromodulators influencing cognitive performance and synaptic plasticity. While the majority of literature concerns adrenal- and gonadectomized animals, very little is known about the “natural” endogenous release of hormones during learning. Therefore, we measured blood and brain (hippocampus, prefrontal cortex) testosterone, estradiol, and corticosterone concentrations of intact male rats undergoing a spatial learning paradigm which is known to reinforce hippocampal plasticity. We found significant modulations of all investigated hormones over the training course. Corticosterone and testosterone were correlated manifold with behavior, while estradiol expressed fewer correlations. In the recall session, testosterone was tightly coupled to reference memory (RM) performance, which is crucial for reinforcement of synaptic plasticity in the dentate gyrus. Intriguingly, prefrontal cortex and hippocampal levels related differentially to RM performance. Correlations of testosterone and corticosterone switched from unspecific activity to specific cognitive functions over training. Correspondingly, exogenous application of testosterone revealed different effects on synaptic and neuronal plasticity in trained versus untrained animals. While hippocampal long-term potentiation (LTP) of the field excitatory postsynaptic potential (fEPSP) was prolonged in untrained rats, both the fEPSP- and the population spike amplitude (PSA)-LTP was impaired in trained rats. Behavioral performance was unaffected, but correlations of hippocampal field potentials with behavior were decoupled in treated rats. The data provide important evidence that besides adrenal, also gonadal steroids play a mechanistic role in linking synaptic plasticity to cognitive performance.

Highlights

Considerable effects of steroidal hormones on cognitive performance and synaptic plasticity in vitro and in vivo have been described (McGaugh et al, 1975; McEwen et al, 1977; Joels and de Kloet, 1989; Pavlides et al, 1993; Sinopoli et al, 2006)
Learning performance of training groups was assessed by the two parameters latency and reference memory errors (RME), which reflect the long-term memory for the spatial location of the holes
Recall was significantly better at the end of session 2 compared to the beginning (RME p = 0.006; latency p < 0.001), indicating that the animals acquired the task in this session (Figure 1C)

Summary

Introduction

Considerable effects of steroidal hormones on cognitive performance and synaptic plasticity in vitro and in vivo have been described (McGaugh et al, 1975; McEwen et al, 1977; Joels and de Kloet, 1989; Pavlides et al, 1993; Sinopoli et al, 2006). The present study aimed at contributing to fill this gap by investigating functional relations of steroids to behavior, memory, and hippocampal synaptic plasticity during a spatial learning task in intact male rats. We chose a spatial learning paradigm, which is known to affect plastic processes, i.e., reinforce long-term potentiation (LTP) in the dentate gyrus. Such behavioral LTP reinforcement is characterized by the transference of an electrically induced protein synthesisindependent early LTP, present for 8 h, into a protein synthesisdependent late form, lasting for 24 h and more (Seidenbecher et al, 1997; Uzakov et al, 2005). It is hypothesized that synthesis of plasticity-related proteins is stimulated by concurrent learninginduced heterosynaptic activation and that processing of these proteins by the electrically stimulated synapses results in the prolonged potentiation

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