Frank Beach Award Winner: Steroids as neuromodulators of brain circuits and behavior

Abstract

Neurons communicate primarily via action potentials that transmit information on the timescale of milliseconds. Neurons also integrate information via alterations in gene transcription and protein translation that are sustained for hours to days after initiation. Positioned between these two signaling timescales are the minute-by-minute actions of neuromodulators. Over the course of minutes, the classical neuromodulators (such as serotonin, dopamine, octopamine, and norepinephrine) can alter and/or stabilize neural circuit patterning as well as behavioral states. Neuromodulators allow many flexible outputs from neural circuits and can encode information content into the firing state of neural networks. The idea that steroid molecules can operate as genuine behavioral neuromodulators - synthesized by and acting within brain circuits on a minute-by-minute timescale - has gained traction in recent years. Evidence for brain steroid synthesis at synaptic terminals has converged with evidence for the rapid actions of brain-derived steroids on neural circuits and behavior. The general principle emerging from this work is that the production of steroid hormones within brain circuits can alter their functional connectivity and shift sensory representations by enhancing their information coding. Steroids produced in the brain can therefore change the information content of neuronal networks to rapidly modulate sensory experience and sensorimotor functions.

Reproductive Aging: Perimenopause and Psychopathological Symptoms

“…Connectomics has already begun to map out large-scale neural circuit diagrams, including ultrastructural analysis of the human brain [109,110]. It is noteworthy that neural circuits do not have fixed connective properties and the relative concentrations and mixture of neuromodulators at any given moment can provide yet another layer of dynamic functional connections within a circuit [109].…”

“…on the timescale of hours or days) [109]. The production of steroid hormones within brain circuits can rapidly modulate their functional connectivity, thereby affecting the behavior [109]. Effects of long-term 17-β estradiol (E2)…”

“…Interventional research on early postmenopausal women suggests that estrogen effects on serotonergic function may actually be a key mechanism relating mood and cognitive symptoms in the menopausal transition [112]. Many biogenic amines like serotonin, dopamine, and norepinephrine can directly shift sensory representations through modulatory actions in the frontal lobe, midbrain, and thalamus [109]. A substantial body of evidence has already linked estrogen and serotonin, as well as estrogen and dopamine in the central nervous system [113,114].…”

Cellular and Molecular Mechanisms of the Effects of Sex Hormones on the Nervous System

“…Recent research demonstrated that steroids can function in a "neurotransmitter-like" way, being synthesized at precise spatial locations within neural circuits in the brain and acting within minutes as local neuromodulators that rapidly regulate cognitive functions and behavior [24][25][26][27].…”

Effects of estradiol on neural responses to social signals in female túngara frogs

“…For example, estradiol shapes auditory tuning in midshipmen fish so that, during the breeding season, females are more sensitive to the harmonics in the calls of courting males, which enhances the adaptive coupling of the sender and the receiver for reproductive success (Sisneros, 2009a,b,c;Sisneros et al, 2004). Similar mechanisms of estradiol-dependent modulation of acoustic communication circuits are present in birds in response to plasma estradiol (Maney et al, 2006(Maney et al, , 2008Maney and Pinaud, 2011;Sanford et al, 2010) and locally produced neuroestrogens (Krentzel and Remage-Healey, 2015;Pawlisch and Remage-Healey, 2015;Remage-Healey, 2012, 2014RemageHealey et al, 2010RemageHealey et al, , 2008Remage-Healey and Joshi, 2012).…”