Postnatal maturation of GABAergic transmission in the rat basolateral amygdala

The adolescent age is associated with lability of mood and emotion. The onset of depression and anxiety disorders peaks during adolescence and there are differences in symptomology during adolescence. This points to differences in the adolescent neural circuitry that underlies mood and emotion, such as the amygdala. The human adolescent amygdala is more responsive to evocative stimuli, hinting to less local inhibitory regulation of the amygdala, but this has not been explored in adolescents. The amygdala, including the lateral nucleus (LAT) of the basolateral amygdala complex, is sensitive to stress. The amygdala undergoes maturational processes during adolescence, and therefore may be more vulnerable to harmful effects of stress during this time period. However, little is known about the effects of stress on the LAT during adolescence. GABAergic inhibition is a key regulator of LAT activity. Therefore, the purpose of this study was to test whether there are differences in the local GABAergic regulation of the rat adolescent LAT, and differences in its sensitivity to repeated stress. We found that LAT projection neurons are subjected to weaker GABAergic inhibition during adolescence. Repeated stress reduced in vivo endogenous and exogenous GABAergic inhibition of LAT projection neurons in adolescent rats. Furthermore, repeated stress decreased measures of presynaptic GABA function and interneuron activity in adolescent rats. In contrast, repeated stress enhanced glutamatergic drive of LAT projection neurons in adult rats. These results demonstrate age differences in GABAergic regulation of the LAT, and age differences in the mechanism for the effects of repeated stress on LAT neuron activity. These findings provide a substrate for increased mood lability in adolescents, and provide a substrate by which adolescent repeated stress can induce distinct behavioral outcomes and psychiatric symptoms.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Zhang

Rosenkranz

2016

“…Each of these components contribute to the fine tuning of the excitatory/inhibitory balance in the brain and are likely to play important roles in regulating developmental stage-specific alterations in neural plasticity and behavior. Within the amygdala, a number of changes in GABAergic function occur during pre-adolescence, including the emergence and maturation of parvalbumin-expressing GABAergic interneurons, as well as decreases in the density of GABAergic cell bodies and increases in the density of GABAergic fibers (Ehrlich et al, 2013). These changes appear to play a critical role in several of the qualitative changes in fear learning that occur during this stage.…”

Section: Developmental Regulation Of Fear-related Plasticitymentioning

confidence: 99%

Sensitive Periods in Affective Development: Nonlinear Maturation of Fear Learning

Hartley

Lee

2014

At specific maturational stages, neural circuits enter sensitive periods of heightened plasticity, during which the development of both brain and behavior are highly receptive to particular experiential information. A relatively advanced understanding of the regulatory mechanisms governing the initiation, closure, and reinstatement of sensitive period plasticity has emerged from extensive research examining the development of the visual system. In this article, we discuss a large body of work characterizing the pronounced nonlinear changes in fear learning and extinction that occur from childhood through adulthood, and their underlying neural substrates. We draw upon the model of sensitive period regulation within the visual system, and present burgeoning evidence suggesting that parallel mechanisms may regulate the qualitative changes in fear learning across development.

“…Neurons in the BLA mature prominently throughout infancy and adolescence (Berdel et al, 1997b;Ryan et al, 2014), when amygdala-dependent emotional behavior also undergoes marked development (Landers and Sullivan, 2012;King et al, 2014). During this period, fold changes are observed in the intrinsic membrane properties, action potential (AP) kinetics, and synaptic and voltage-gated currents of BLA principal neurons Ehrlich et al, 2013), which comprise~85% of neurons in the nucleus (McDonald, 1985). We propose that heightened plasticity of amygdala neurons during infancy and adolescence contributes to the emergence of deficits following PS.…”

Section: Introductionmentioning

confidence: 99%

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

Ehrlich

Rainnie

2015

Prenatal stress (PS) is a risk factor for neurodevelopmental disorders with diverse ages of onset and socioemotional symptoms. Some PS-linked disorders involve characteristic social deficits, such as autism spectrum disorders and schizophrenia, but PS also promotes anxiety disorders. We propose the diversity of symptoms following PS arises from perturbations to early brain development. To this end, we characterized the effects of PS on the developmental trajectory of physiology of the amygdala, a late-developing center for socioemotional control. We found that PS dampened socioemotional behavior and reduced amygdala neuron excitability in offspring during infancy (at postnatal days (P)10, 14, 17 and 21), preadolescence (day 28), and adulthood (day 60). PS offspring in infancy produced fewer isolation-induced vocalizations and in adulthood exhibited less anxiety-like behavior and deficits in social interaction. PS neurons had a more hyperpolarized resting membrane potential from infancy to adulthood and produced fewer action potentials. Moreover, adult amygdala neurons from PS animals expressed larger action potential afterhyperpolarizations and H-current relative to controls, further limiting excitability. Our results suggest that PS can suppress socioemotional behavior throughout development and produce age-specific alterations to amygdala physiology.