Age‐dependent, steroid‐specific effects of oestrogen on long‐term potentiation in rat hippocampal slices

Abstract

Long‐term potentiation (LTP) of hippocampal population spike responses and excitatory postsynaptic potentials (EPSPs) from area CA1 stratum pyramidale was induced in slices of rat hippocampus maintained in vitro following brief high‐frequency stimulation (HFS) of the Schaffer collateral‐commissural pathway. When administered to slices prior to HFS, 17β‐oestradiol (OE2), at a concentration as low as 0.1 nm, suppressed the magnitude of the resultant HFS‐induced potentiation in slices from prepubertal animals (3 and 4 weeks old) of both sexes. OE2 did not suppress the induction of LTP in slices taken from the hippocampus of adult animals of either sex. There was no similar suppressant effect of 17α‐oestradiol (OE1), progesterone (PRG) or testosterone (TST) on LTP in the young animals, even at a concentration 100 times greater than was effective for OE2. The anti‐oestrogen compound tamoxifen (TMX; 1.0 and 10.0 μm), which acts principally at intracellular binding sites within the nucleus, was without effect in diminishing the suppressant effect of OE2 on LTP in slices from young animals. The LTP observed in slices from both 3‐week‐old and adult rats was AP5 sensitive and thus was shown to be dependent on activation of NMDA receptors. Results from whole‐cell recording experiments suggested that OE2 caused the LTP‐suppressant effect through an action on NMDA‐mediated currents. These data suggest an age‐dependent and possibly a surface membrane receptor‐mediated role for oestrogens in modulating the efficacy of input‐output properties of CA1 neurones produced by HFS during a critical period in development.

Progesterone receptors: Form and function in brain

“…P 4 (10 μM) reportedly has no effect on LTP (CA1 slices from 4 week-old rats), but no non-drug control was used in this study [151]. In another study, P 4 (8 -10 M, in CA1 slices) significantly enhanced synaptic transmission, as seen by an increased field potential and population spike amplitude; however, following a seizure-induced tetanus, P 4 decreased the field potential, the population spike responses, and the duration of after-discharges [152].…”

Progesterone regulation of synaptic transmission and plasticity in rodent hippocampus

“…One study reported that P4 (10 ‫5מ‬ M) had no effect on long-term potentiation (LTP) recorded in vitro from hippocampal (CA1) slices in adult rats, but no non-drug control was graphed to compare the experimental (P4) condition, and the experimental subjects were a combined group of gonadally intact male and female rats (Ito et al 1999). Another study reported that P4 (10 ‫8מ‬ M) significantly enhanced synaptic transmission in CA1, but following seizure-inducing tetanus, P4 decreased both field potential and population spike responses and decreased the duration of after-discharges (Edwards et al 2000).…”

Aromatase Inhibition Abolishes LTP Generation in Female But Not in Male Mice

“…The effects of estradiol on spine density and LTP were frequently shown by either using ovariectomized animals, which had been treated systemically with estradiol (Gould et al, 1990;Warren et al, 1995;Có rdoba Montoya and Carrer, 1997;Smith and McMahon, 2005;Kramár et al, 2009), by applying estradiol to acute slices of mostly male rats (Foy et al, 1999;Ito et al, 1999;Mukai et al, 2007;Kramár et al, 2009), or by using mixed hippocampal slice cultures from neonatal males and females (Murphy and Segal, 1996;Kretz et al, 2004;Mendez et al, 2011). Thus, the vast majority of studies do not consider the potential differences between males and females.…”