Stress is a major modulator of neuronal networks and its consequences can be transmitted to others. With this in mind, a team from University of Calgary embarked on a journey to decipher whether transmitted stress has the same consequences on synapses as authentic stress (Nature Neuroscience 21 393). Their findings in mice suggest that the lasting effects on synapses are the same for both authentic and transmitted stress, with implications for other stressful events.

Stress induces metaplasticity
In the experiments, the authors subjected mice to footshock stress for 5 min and, upon returning them to their homecage, to high-frequency electrical stimulation for 30 min. They discovered that acute stress resulted in persistent changes at glutamate synapses (glutamate is the major excitatory neurotransmitter in the nervous system) on corticotropin-releasing hormone (CRH) neurons. This enables the induction of metaplasticity, activity-dependent changes in neural functions that modulate subsequent synaptic plasticity. The CRH neurons are found in the paraventricular nucleus of the hypothalamus, one of the most important autonomic control centres in the brain, and their activation is necessary for the rise of the endocrine response to stress.

Pheromones help transmit stress
To study the effect of social interactions on metaplasticity, mice were subjected to footshock or a novel environment for 5 min and returned to a same-sex control partner in the homecage for the next 30 min. Interestingly, stress is transmitted by the release of alarm pheromones, predominantly from glands in the anogenital area, which are sensed by the partner during investigative behaviour. The triggering of this type of behaviour and synaptic priming require the activity of CRH neurons (which the authors determined using whole-cell recordings from CRH neurons in hypothalamic slices).

This experiment suggested that transmitted stress primes glutamate synapses in male and female subjects with different sensitivity and, importantly, that the effects of authentic stress in females are reduced by the presence of a partner.

In another experiment, the team showed that the synaptic priming induced by transmitted stress can also be propagated by a partner mouse to a tertiary group member, with similar effects (the same synaptic load).

The findings of this study indicate the importance of mitigating the effects of stress and how the information extracted from the experience of a distressed subject can have adaptive benefits. Moreover, the impacted neuronal circuits can this way prepare the individuals for subsequent challenges.