G.Z. Huang, C.S. Woolley, “Estradiol acutely suppresses inhibition in the hippocampus through a sex-specific endocannabinoid and mGluR-dependent mechanism,” Neuron, 74:801-08, 2012.
The ovarian reproductive hormone estradiol (E2) is synthesized in the hippocampus of both males and females, where it is thought to affect hippocampal functions such as memory and mood-related behavior by increasing the excitability of neurons. To nail down just how this works, Guang Zhe Huang and Catherine Woolley of Northwestern University recorded electrical signals from rat hippocampal slices exposed to E2. They found that, in addition to its excitatory effects, E2 suppresses inhibitory synaptic transmission—as if E2 not only steps on the gas to activate neurons, but disables the brakes as well. The team also found that this pathway occurs only in females.
E2 acts on inhibitory neurons by enlisting compounds called endocannabinoids. Surprisingly, the research team found that the endocannabinoid involved was different than the one that had been observed in previous studies of hippocampal signaling. The reason for this disparity, they realized, was that they had used female rats, while earlier work had used male rats.
Paul Mermelstein of the University of Minnesota points out that the vast majority of basic neuroscience experiments are done in male animals. “There may be a whole infrastructure in terms of endocannabinoid signaling present in the female brain that’s not present in males,” he says.
The next steps
Woolley would like to find out how these sex differences in synaptic modulation affect the functioning of the hippocampus. One possibility she’s exploring if E2 is important in regulating epileptic seizures; another is whether E2-endocannabinoid signaling is involved in anxiety.