Qualitatively different effect of repeated stress during adolescence on principal neuron morphology across lateral and basal nuclei of the rat amygdala

Abstract

Repeated stress can elicit symptoms of depression and anxiety. The amygdala is a significant contributor to the expression of emotion and the basolateral amygdala (BLA) is a major target for the effects of stress on emotion. The adolescent time period may be particularly susceptible to the effects of stress on emotion. While repeated stress has been demonstrated to modify the morphology of BLA neurons in adult rats, little is known about its effects on BLA neurons during adolescence. This study tests the effects of repeated stress during adolescence on BLA neuronal morphology, and whether these are similar to the effects of stress during adulthood. The BLA includes the basal (BA) and lateral (LAT) nuclei, which are differentially responsive to stress in adults. Therefore, effects of stress during adolescence were compared between the BA and LAT nuclei. Morphological features of reconstructed BLA neurons were examined using Golgi-Cox stained tissue from control or repeated restraint stress exposed rats. We found subtle dendritic growth coupled with loss of spines after repeated stress during adolescence. The magnitude and dendritic location of these differences varied between the BA and LAT nuclei in strong contrast to the stress-induced increases in spine number seen in adults. These results demonstrate that repeated stress during adolescence has markedly different effects on BLA neuronal morphology, and the extent of these changes are BLA nucleus-dependent. Moreover, altered neuroanatomy was associated with age-dependent effects of repeated stress on generalization of fear, and may point to the necessity for different approaches to target stress-induced changes in adolescents.

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

“…In contrast, there was little evidence for increased glutamatergic drive after repeated stress in adolescent rats. In fact, a decrease of mEPSC frequency was observed, consistent with recent findings that repeated stress decreases the number of spines on LAT neurons in adolescent rats (Tsai et al, 2014;Padival et al, 2015).…”

“…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). In contrast, there was little evidence for increased glutamatergic drive after repeated stress in adolescent rats.…”

“…Studies have repeatedly demonstrated that the increased activity of the amygdala in adult male rats after stress parallels increased anxiety (Vyas et al, 2004;DoremusFitzwater et al, 2009;Rosenkranz et al, 2010) and production of behaviors that rely on the BLA, such as such as freezing in response to a fear-conditioned cue (Conrad et al, 1999;Rau et al, 2005;Rodriguez Manzanares et al, 2005;ToledoRodriguez and Sandi, 2007;Atchley et al, 2012;Zhang and Rosenkranz, 2013). Relatively less is known about the effects of stress on amygdala-dependent behaviors in adolescents; however, in several studies increased fear conditioning is accompanied by an impairment of fear extinction in adolescents and enhanced generalization of fear (Morrissey et al, 2011;Zhang and Rosenkranz, 2013;Muller et al, 2014;Padival et al, 2015). Both of these processes are sensitive to GABA within the BLA (Davis and Myers, 2002;Shaban et al, 2006;Lin et al, 2009;Sangha et al, 2009;Makkar et al, 2010;Lange et al, 2014).…”

Opposing effects of traumatic brain injury on excitatory synaptic function in the lateral amygdala in the absence and presence of preinjury stress

“…This may be due to differential effects of stress between LA and BLA neurons. For example, it has been reported that chronic stress has little impact on total dendritic length within LA neurons in adult mice (65–73 days old; similar to the age at which mice received foot‐shock stress in this study; Padival et al, ). Therefore, the increase in sEPSC activity in the absence of a significant increase in total dendritic length is in agreement with published data when taking the region of the amygdala and the age of the mice into account.…”

Disruption of behavior and brain metabolism in artificially reared rats

“…Neural activity, neurotransmitter release, and growth factors are also disrupted during social isolation in rats before or after weaning (Cirulli et al, 2003;Chatterjee et al, 2007;Le on-Rodr ıguez and Dueñas, 2013;Toda et al, 2014;Wang et al, 2015), and these alterations associate with glial underdevelopments. The main structures affected are amygdala (Fleming et al, 1994;Sanchez et al, 1995;Lyons et al, 2010;Lukkes et al, 2012;Toda et al, 2014;Padival et al, 2015), the medial prefrontal cortex (Silva-G omez et al, 2003;Braun et al, 2009;Miyazaki et al, 2012;Wall et al, 2012;Tada et al, 2016), hippocampus (Silva-G omez et al, 2003;Bonab et al, 2012;Wang and Gondr e-Lewis, 2013), and the HPA axis (Akbari et al, 2008;Daniels et al, 2009;Vargas et al, 2016).…”