Distinct Effects of Repeated Restraint Stress on Basolateral Amygdala Neuronal Membrane Properties in Resilient Adolescent and Adult Rats

Abstract

Severe and repeated stress has damaging effects on health, including initiation of depression and anxiety. Stress that occurs during development has long-lasting and particularly damaging effects on emotion. The basolateral amygdala (BLA) plays a key role in many affective behaviors, and repeated stress causes different forms of BLA hyperactivity in adolescent and adult rats. However, the mechanism is not known. Furthermore, not every individual is susceptible to the negative consequences of stress. Differences in the effects of stress on the BLA might contribute to determine whether an individual will be vulnerable or resilient to the effects of stress on emotion. The purpose of this study is to test the cellular underpinnings for age dependency of BLA hyperactivity after stress, and whether protective changes occur in resilient individuals. To test this, the effects of repeated stress on membrane excitability and other membrane properties of BLA principal neurons were compared between adult and adolescent rats, and between vulnerable and resilient rats, using in vitro whole-cell recordings. Vulnerability was defined by adrenal gland weight, and verified by body weight gain after repeated restraint stress, and fecal pellet production during repeated restraint sessions. We found that repeated stress increased the excitability of BLA neurons, but in a manner that depended on age and BLA subnucleus. Furthermore, stress resilience was associated with an opposite pattern of change, with increased slow afterhyperpolarization (AHP) potential, whereas vulnerability was associated with decreased medium AHP. The opposite outcomes in these two populations were further distinguished by differences of anxiety-like behavior in the elevated plus maze that were correlated with BLA neuronal excitability and AHP. These results demonstrate a substrate for BLA hyperactivity after repeated stress, with distinct membrane properties to target, as well as age-dependent factors that contribute to resilience to the effects of stress.

Effects of Repeated Stress on Age-Dependent GABAergic Regulation of the Lateral Nucleus of the Amygdala

“…For instance, increased excitatory responses to glutamate and increased glutamatergic synaptic transmission. The increased excitatory response to glutamate could be caused by increased neuronal membrane excitability (Rosenkranz et al, 2010;Hetzel and Rosenkranz, 2014), increased function of NMDA or AMPA receptors (Adamec et al, 2005;Caudal et al, 2010;Mozhui et al, 2010;Suvrathan et al, 2014), reduced glutamatergic drive of GABAergic networks (Masneuf et al, 2014), or upregulation of glutamatergic receptors (Lei and Tejani-Butt, 2010;Gan et al, 2014). Increased glutamatergic synaptic transmission could be caused by increased glutamatergic inputs, as observed here and in other studies (Mitra et al, 2005;Vyas et al, 2006;Padival et al, 2013Padival et al, , 2015Suvrathan et al, 2014;Tsai et al, 2014).…”

MicroRNAs as biomarkers of resilience or vulnerability to stress

“…The BLA is important in regulating behavioral and neuroendocrine responses to stress (Grissom and Bhatnagar, 2009) and the structural properties of its cells are affected by repeated stress (Padival et al, 2013). Interestingly, the electrophysiological properties of its cells are different in resilient rats (Hetzel and Rosenkranz, 2014). However, we did not observe significant differences between SL and LL rats in the levels of any microRNA in the BLA.…”

Prenatal Stress Alters the Development of Socioemotional Behavior and Amygdala Neuron Excitability in Rats

“…A recent study compared BLA principal neurons of rats inherently resilient or vulnerable to stress (Hetzel and Rosenkranz, 2014). Interestingly, BLA neurons from resilient rats shared a number of properties with neurons from adult PS offspring in the present study.…”