Catherine Woolley, PhD
Sex Differences in the Brain: Not what you think
Evidence for latent sex differences in mechanisms of synaptic modulation
The billions of neurons in the brain are wired into circuits through trillions of synapses. The effectiveness of most synapses in transmitting information from one neuron to the next changes with patterns of activity and is controlled by a wide variety of neuromodulators that may be endogenously produced or taken as drugs. We discovered that neurosteroid estrogens (estrogens synthesized directly in the brain) are powerful neuromodulators at work in the brains of both sexes, independent of their roles as hormones. I will discuss studies in rodents demonstrating a surprising role for neurosteroid estrogens in seizures and explain how these studies led to discovery of “latent” sex differences in mechanisms of synaptic modulation. A latent sex difference is one in which a particular stimulus produces the same outcome in both sexes but does so through distinct underlying mechanisms in each sex. The broader implications of latent sex differences include that molecular mechanisms targeted for drug development may differ between males and females even in the absence of an overt sex difference in behavior or disease.