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Limited prefrontal cortical regulation over the basolateral amygdala in adolescent rats.

ABSTRACT: Cognitive regulation of emotion develops from childhood into adulthood. This occurs in parallel with maturation of prefrontal cortical (PFC) regulation over the amygdala. The cellular substrates for this regulation may include PFC activation of inhibitory GABAergic elements in the amygdala. The purpose of this study was to determine whether PFC regulation over basolateral amygdala area (BLA) in vivo is immature in adolescence, and if this is due to immaturity of GABAergic elements or PFC excitatory inputs. Using in vivo extracellular electrophysiological recordings from anesthetized male rats we found that in vivo summation of PFC inputs to the BLA was less regulated by GABAergic inhibition in adolescents (postnatal day 39) than adults (postnatal day 72-75). In addition, stimulation of either prelimbic or infralimbic PFC evokes weaker inhibition over basal (BA) and lateral (LAT) nuclei of the BLA in adolescents. This was dictated by both weak recruitment of inhibition in LAT and weak excitatory effects of PFC in BA. The current results may contribute to differences in adolescent cognitive regulation of emotion. These findings identify specific elements that undergo adolescent maturation and may therefore be sensitive to environmental disruptions that increase risk for psychiatric disorders.

SUBMITTER: Selleck RA

PROVIDER: S-EPMC6249319 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Limited prefrontal cortical regulation over the basolateral amygdala in adolescent rats.

Selleck Ryan A RA Zhang Wei W Mercier Hannah D. HD Padival Mallika M Rosenkranz J Amiel JA

Scientific reports 20181121 1

Cognitive regulation of emotion develops from childhood into adulthood. This occurs in parallel with maturation of prefrontal cortical (PFC) regulation over the amygdala. The cellular substrates for this regulation may include PFC activation of inhibitory GABAergic elements in the amygdala. The purpose of this study was to determine whether PFC regulation over basolateral amygdala area (BLA) in vivo is immature in adolescence, and if this is due to immaturity of GABAergic elements or PFC excitat ...[more]

PMID: 30464293

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Project description:To study the molecular mediators of naturally rewarding effects of palatable food we used a model of palatable âsnackingâ (Ulrich-Lai et al., 2007) in which rats are given chronic, brief access to a limited amount of sucrose solution (30%). Single housed, male Long-Evans rats (250g) (n=12 per group) from Harlan Labs (Indianapolis, IN) received normal rat chow (Harlan Teklad) and water ad libitum for the duration of the experiment. After a one-week period of acclimation, rats were randomly assigned to drink treatment groups of either 30% sucrose solution or water. Rats received a 14-day regimen of twice daily (9:30 and 15:30) brief (maximum of 30 minutes) limited (up to 4 mL) access of their assigned drink solution. Drink solutions were delivered via a graduated sipper placed onto the cage top in addition to the existing water bottle and sippers were immediately removed when the animal had consumed 4mL or after the 30-minute access period, whichever occurred first. Drink intake, food intake, and body weight were monitored throughout the experiment to verify that the rats learned to drink sucrose, that they adjusted chow intake for calories consumed from sucrose (~10%), and that there was no effect on body weight gain as is normally seen with this model (Ulrich-Lai et al., 2007). Drink treatment terminated on day 14 and at 8:00 on the morning of day 15, the rats were sacrificed by rapid decapitation. BLA tissue was dissected, RNA extracted, and gene expression changes between water and sucrose groups were accessed by microarray. We used microarray to assess the changes in gene expression in the BLA of rats that have had a history of sucrose snacks (n=12) vs control (n=12). Rats received access (up to 4 mL) to extra bottles containing water (control) or 30% sucrose twice daily for 14 days. Rats had ab lib access to chow and water for the duration of the experiment. Rats were sacrificed the morning of day 15 and the BLA was removed for microarray analysis. Functional cluster analysis was performed on the list of 145 significantly upregulated genes using Ingenuity Pathway Analysis (Ingenuity Systems, Redwood City, CA). See supplementary file at the foot of this record.

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Project description:Adolescence is a developmental period marked by robust neural alterations and heightened vulnerability to stress, a factor that is highly associated with increased risk for emotional processing deficits, such as anxiety. Stress-induced upregulation of the dynorphin/kappa opioid receptor (DYN/KOP) system is thought to, in part, underlie the negative affect associated with stress. The basolateral amygdala (BLA) is a key structure involved in anxiety, and neuromodulatory systems, such as the DYN/KOP system, can 1) regulate BLA neural activity in an age-dependent manner in stress-naïve animals and 2) underlie stress-induced anxiety in adults. However, the role of the DYN/KOP system in modulating stress-induced anxiety in adolescents is unknown. To test this, we examined the impact of an acute, 2-day forced swim stress (FSS - 10 min each day) on adolescent (~postnatal day (P) 35) and adult Sprague-Dawley rats (~P70), followed by behavioral, molecular and electrophysiological assessment 24 h following FSS. Adolescent males, but not adult males or females of either age, demonstrated social anxiety-like behavioral alterations indexed via significantly reduced social investigation and preference when tested 24 h following FSS. Conversely, adult males exhibited increased social preference. While there were no FSS-induced changes in expression of genes related to the DYN/KOP system in the BLA, these behavioral alterations were associated with alterations in BLA KOP function. Specifically, while GABA transmission in BLA pyramidal neurons from non-stressed adolescent males responded variably (potentiated, suppressed, or was unchanged) to the KOP agonist, U69593, U69593 significantly inhibited BLA GABA transmission in the majority of neurons from stressed adolescent males, consistent with the observed anxiogenic phenotype in stressed adolescent males. This is the first study to demonstrate stress-induced alterations in BLA KOP function that may contribute to stress-induced social anxiety in adolescent males. Importantly, these findings provide evidence for potential KOP-dependent mechanisms that may contribute to pathophysiological interactions with subsequent stress challenges.

Dataset Information

Limited prefrontal cortical regulation over the basolateral amygdala in adolescent rats.

Publications

Limited prefrontal cortical regulation over the basolateral amygdala in adolescent rats.

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