Acute Physiological Effects of Brain-Generated 17β-Estradiol in the Rodent Primary Auditory Cortex

Abstract

The neuroactive steroid hormone 17β-estradiol (E2) modulates synaptic activity and plasticity in both endocrine and non-endocrine forebrain regions of males and females of a variety of species. Research conducted in songbirds has established that E2 is rapidly synthesized in the auditory forebrain in response to salient auditory experience, and this locally-synthesized E2 contributes to auditory signal processing and learning. Despite the role of E2 in auditory processing and learning, together with its effects on synaptic activity and plasticity in non-sensory regions of the mammalian forebrain, particularly the hippocampus, the modulatory actions of E2 on synaptic plasticity mechanisms underlying learning and memory have not been directly investigated in the mammalian auditory forebrain. The studies described in this thesis examined the modulatory role of E2 in synaptic activity and plasticity in the rodent auditory forebrain. First, immunohistochemistry (IHC) was used to characterize neocortical expression of the estrogen synthetic enzyme aromatase in adult male rats. Aromatase was expressed by a large population of neurons in medial prefrontal cortex (mPFC), primary somatosensory cortex (S1), primary auditory cortex (A1), and primary visual cortex (V1). Next, in vivo field recordings were used to determine the effects of acute, bidirectional E2 manipulations on short- and long-term synaptic plasticity (paired-pulse responses and long-term potentiation; LTP) in A1. E2 significantly reduced the threshold for LTP induction at layer IV, thalamocortical synapses, whereas suppression of local E2 production by aromatase inhibition significantly reduced LTP induction at layer II/III, intracortical synapses. Acute E2 manipulations did not significantly alter paired-pulse responses in A1, suggesting a postsynaptic locus of the modulatory effects of E2 on LTP. Finally, ex vivo whole-cell recordings were used to explore the mechanisms underlying the E2-dependent modulation of LTP in A1. Agonist-evoked excitatory and inhibitory synaptic currents in A1 were sensitive to bidirectional E2 manipulations in a layer-specific manner, suggesting a role for E2 in maintaining the balance of excitation and inhibition in this region. These findings further our understanding of the modulatory role of E2 in sensory system function and plasticity and have broad implications for the study of learning and memory.