Effects of corticosterone on mild auditory fear conditioning and extinction; role of sex and training paradigm

Multiple lines of evidence suggest that glucocorticoid hormones enhance memory consolidation of fearful events. However, most of these studies involve male individuals. Since anxiety, fear, and fear-associated disorders present differently in male and female subjects we investigated in mice whether male and female mice perform differently in a mild, auditory fear conditioning task and tested the modulatory role of glucocorticoid hormones. Using an auditory fear conditioning paradigm with different footshock intensities (0.1, 0.2, and 0.4 mA) and frequencies (1× or 3×), we find that intraperitoneal injections with corticosterone (2 mg/kg) immediately after training, altered freezing behavior when repeated footshocks were applied, and that the direction of the effects were opposite in male and female mice. Effects were independent of footshock intensity. In male mice, corticosterone consistently increased freezing behavior in response to the tone, whereas in female mice, corticosterone reduced freezing behavior 24 h after training. These effects were not related to the phase of the oestrous cycle. In addition, corticosterone enhanced extinction learning for all tones, in both male and female mice. These results emphasize that glucocorticoid hormones influence memory consolidation and retrieval, and underscore sex-specific effects of glucocorticoid hormones in modulating conditioned fear responses.</p

Shaping Memories via Stress:A Synaptic Engram Perspective

Stress modulates the activity of various memory systems and can thereby guide behavioral interaction with the environment in an adaptive or maladaptive manner. At the cellular level, a large body of evidence indicates that (nor)adrenaline and glucocorticoid release induced by acute stress exposure affects synapse function and synaptic plasticity, which are critical substrates for learning and memory. Recent evidence suggests that memories are supported in the brain by sparsely distributed neurons within networks, termed engram cell ensembles. While the physiological and molecular effects of stress on the synapse are increasingly well characterized, how these synaptic modifications shape the multiscale dynamics of engram cell ensembles is still poorly understood. In this review, we discuss and integrate recent information on how acute stress affects synapse function and how this may alter engram cell ensembles and their synaptic connectivity to shape memory strength and memory precision. We provide a mechanistic framework of a synaptic engram under stress and put forward outstanding questions that address knowledge gaps in our understanding of the mechanisms that underlie stress-induced memory modulation

An emerging role for microglia in stress-effects on memory

Stressful experiences evoke, among others, a rapid increase in brain (nor)epinephrine (NE) levels and a slower increase in glucocorticoid hormones (GCs) in the brain. Microglia are key regulators of neuronal function and contain receptors for NE and GCs. These brain cells may therefore potentially be involved in modulating stress effects on neuronal function and learning and memory. In this review, we discuss that stress induces (1) an increase in microglial numbers as well as (2) a shift toward a pro-inflammatory profile. These microglia have (3) impaired crosstalk with neurons and (4) disrupted glutamate signaling. Moreover, microglial immune responses after stress (5) alter the kynurenine pathway through metabolites that impair glutamatergic transmission. All these effects could be involved in the impairments in memory and in synaptic plasticity caused by (prolonged) stress, implicating microglia as a potential novel target in stress-related memory impairments