From anxiety to autism: spectrum of abnormal social behaviors modeled by progressive disruption of inhibitory neuronal function in the basolateral amygdala in Wistar rats

Truitt, William A.; Sajdyk, Tammy J.; Dietrich, Amy D.; Oberlin, Brandon G.; McDougle, Christopher J.; Shekhar, Anantha

doi:10.1007/s00213-006-0674-y

Cited by 68 publications

(70 citation statements)

References 83 publications

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“…The reversal potential in principal neurons became more hyperpolarized with age, shifting from approximately Ϫ55 mV at P7 to Ϫ70 mV at P21. The magnitude and time course of this change matched those identified in cell-attached recordings of hippocampal pyramidal neurons, which exhibit a similar hyperpolarization of the GABA A reversal potential of ϳ15 mV between birth and P17 (Tyzio et al 2008). The existence of excitatory GABA A receptor-mediated potentials during brain development has been well documented (Ben-Ari 2002;Owens and Kriegstein 2002).…”

Section: Discussionsupporting

confidence: 58%

Postnatal maturation of GABAergic transmission in the rat basolateral amygdala

Ehrlich

Ryan

Hazra

et al. 2013

Journal of Neurophysiology

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Section: Discussionsupporting

confidence: 58%

Postnatal maturation of GABAergic transmission in the rat basolateral amygdala

Ehrlich

Ryan

Hazra

et al. 2013

Journal of Neurophysiology

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“…Upon arrival at the facility, rats were individually housed in a temperature-controlled room (22 1C) and kept on a 12-h light-dark cycle (lights on at 0700 hours) with free access to food and water for at least 1 week before behavioral testing (Truitt et al, 2007). Rats were handled daily for a minimum of 3 days before any behavior testing.…”

Section: Animalsmentioning

confidence: 99%

“…However, the presence of a conspecific is at the core of the social interaction (SI) test (File and Hyde, 1978). Previously, we developed a modified version of the SI test, termed as the social interaction-habituation test (SI-hab), which permits using the same conspecific partner repeatedly to investigate the regulation of anxiety-like behavior, by social familiarity (Truitt et al, 2007). Social familiarity, as investigated by SI-hab in rats, reduces chronic anxiety-like behavior induced by pharmacological activation of the basolateral amygdala (BLA) (Truitt et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…Previously, we developed a modified version of the SI test, termed as the social interaction-habituation test (SI-hab), which permits using the same conspecific partner repeatedly to investigate the regulation of anxiety-like behavior, by social familiarity (Truitt et al, 2007). Social familiarity, as investigated by SI-hab in rats, reduces chronic anxiety-like behavior induced by pharmacological activation of the basolateral amygdala (BLA) (Truitt et al, 2007). In addition, this ability of social familiarity to inhibit anxiety-like behavior was dependent on a subpopulation of inhibitory BLA interneurons that may be activated by inputs from the medial prefrontal cortex (mPFC).…”

Section: Introductionmentioning

confidence: 99%

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The Role of the Medial Prefrontal Cortex in Regulating Social Familiarity-Induced Anxiolysis

Lungwitz

Stuber

Johnson

et al. 2013

Neuropsychopharmacol

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Overcoming specific fears and subsequent anxiety can be greatly enhanced by the presence of familiar social partners, but the neural circuitry that controls this phenomenon remains unclear. To overcome this, the social interaction (SI) habituation test was developed in this lab to systematically investigate the effects of social familiarity on anxiety-like behavior in rats. Here, we show that social familiarity selectively reduced anxiety-like behaviors induced by an ethological anxiogenic stimulus. The anxiolytic effect of social familiarity could be elicited over multiple training sessions and was specific to both the presence of the anxiogenic stimulus and the familiar social partner. In addition, socially familiar conspecifics served as a safety signal, as anxiety-like responses returned in the absence of the familiar partner. The expression of the social familiarity-induced anxiolysis (SFiA) appears dependent on the prefrontal cortex (PFC), an area associated with cortical regulation of fear and anxiety behaviors. Inhibition of the PFC, with bilateral injections of the GABA A agonist muscimol, selectively blocked the expression of SFiA while having no effect on SI with a novel partner. Finally, the effect of D-cycloserine, a cognitive enhancer that clinically enhances behavioral treatments for anxiety, was investigated with SFiA. D-cycloserine, when paired with familiarity training sessions, selectively enhanced the rate at which SFiA was acquired. Collectively, these outcomes suggest that the PFC has a pivotal role in SFiA, a complex behavior involving the integration of social cues of familiarity with contextual and emotional information to regulate anxiety-like behavior.

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“…Loss of BLA inhibition is expected to lead to increased or disorganized BLA neuron firing along with increased or inappropriate affective responding. Consistent with this, drugs that facilitate GABAergic inhibition in the BLA are anxiolytic (Sanders and Shekhar, 1995a, b;Pidoplichko et al, 2014), while conditions with reduced inhibition within the BLA are anxiogenic Shekhar, 1997, 2000;Rainnie et al, 2004;Truitt et al, 2007Truitt et al, , 2009Almeida-Suhett et al, 2014) and promote generalization of BLA-dependent behaviors (Shaban et al, 2006;Lange et al, 2014). Despite known differences between adults and adolescents in amygdala-mediated affective behavior and psychiatric symptomology associated with amygdala dysfunction, little is known about differences between GABAergic regulation of the BLA between adults and adolescents.…”

Section: Introductionmentioning

confidence: 96%

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

Zhang

Rosenkranz

2016

Neuropsychopharmacol

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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.

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From anxiety to autism: spectrum of abnormal social behaviors modeled by progressive disruption of inhibitory neuronal function in the basolateral amygdala in Wistar rats

Abstract: These models with different gradations of disrupted BLA inhibition could help to study social dysfunction in disorders ranging from social anxiety to autism spectrum disorders.

Cited by 68 publications

References 83 publications

Postnatal maturation of GABAergic transmission in the rat basolateral amygdala

Postnatal maturation of GABAergic transmission in the rat basolateral amygdala

The Role of the Medial Prefrontal Cortex in Regulating Social Familiarity-Induced Anxiolysis

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

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