Increasing Interaction of Amygdalar Afferents with GABAergic Interneurons between Birth and Adulthood

Cunningham, Miles G.; Bhattacharyya, Sujoy; Beneš, Francine M.

doi:10.1093/cercor/bhm183

Cited by 85 publications

(63 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Cholinergic (28) and GABAergic (29) inputs to GABA cells in SO of CA3/2 originate in the septal nuclei, whereas glutamatergic projections (30) originate in the basolateral amygdala (BLa) (31). Experimental stimulation of the BLa is associated with a reduction in the number of GABA cells in sector CA3/2, a pattern remarkably similar to that seen in postmortem studies of SZ (1).…”

Section: Functional Implications Of Gene Expressionsupporting

confidence: 61%

Circuitry-based gene expression profiles in GABA cells of the trisynaptic pathway in schizophrenics versus bipolars

Beneš

Lim

Matzilevich

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Significant reductions in GABAergic cell numbers and/or activity have been demonstrated in the hippocampus of subjects with schizophrenia and bipolar disorder. To understand how different subpopulations of interneurons are regulated, laser microdissection and gene expression profiling have been used to ''deconstruct'' the trisynaptic pathway, so that subtypes of GABA cells could be defined by their location in various layers of CA3/2 and CA1. The results suggest that the cellular endophenotypes for SZ and BD may be determined by multiple factors that include unique susceptibility genes for the respective disorders and altered integration among hippocampal GABA cells with extrinsic and intrinsic afferent fiber systems. The extensive and intricate data that has come from this study has provided insights into how a complex circuit, like the trisynaptic pathway, may be regulated in human hippocampus in both health and disease.GAD67 ͉ potassium ion transport ͉ synaptic transmission ͉ kainate ͉ nicotinic G ene expression plays a central role in the regulation of neural circuitry involved in cognitive behavior. Identifying molecular mechanisms within neurons of complex circuits presents one of the foremost challenges to understanding the human brain. In the past 20 years, postmortem studies of schizophrenia (SZ) and bipolar disorder (BD) have provided evidence for a dysfunction of GABAergic neurons in frontal cortices and hippocampus (1). It is well known that GABAergic interneurons provide potent inhibitory modulation of principle neurons (2) and are critical for the regulation of feed-forward inhibition (3) and oscillatory rhythms (4, 5). A network of genes involved in the regulation of glutamate decarboxylase 67 (GAD 67 ), a key marker for the GABA cell phenotype (6), shows changes in expression in SZ that are different from those seen in BD, suggesting that there may be unique molecular endophenotypes for each disorder. To learn more about the molecular regulation of hippocampal GABA cells in SZ and BD, a combination of laser microdissection (LMD) and gene expression profiling has been used to ''deconstruct'' the trisynaptic pathway into subtypes of GABA neurons defined by their location and connectivity. Several clusters of genes have been examined across a broad array of cellular functions that include transduction, signaling, metabolism, translation, transcription and cell cycle regulation. These clusters have been separately analyzed in various layers and sectors with a preponderance of GABA cells. To our knowledge, this is the first demonstration that the regulation of gene expression in GABA cells varies not only according to diagnosis, but also to location within a complex circuit.

show abstract

Section: Functional Implications Of Gene Expressionsupporting

confidence: 61%

Circuitry-based gene expression profiles in GABA cells of the trisynaptic pathway in schizophrenics versus bipolars

Beneš

Lim

Matzilevich

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Similar developmentally regulated changes have been observed in rodents during their adolescent period, which has been argued to range from as early as postnatal day (P) 28 to at least P60 based on social, cognitive, hormonal, and neurophysiological changes that parallel markers of human adolescence (Tirelli et al 2003;Spear 2011). For example, during rodent adolescence there are significant increases in connectivity between the basolateral amygdala and medial prefrontal cortex (Cunningham et al 2002(Cunningham et al , 2008, changes in the density of monoamine transporters (Moll et al 2000;Bradshaw et al 2016), increases in prefrontal cortex dopamine innervation (Kalsbeek et al 1988), decreases in medial prefrontal cortex neuron number (Markham et al 2007;Willing and Juraska 2015), and reorganization of the amygdala (Rubinow and Juraska 2009;Koss et al 2014). …”

Section: Introductionmentioning

confidence: 74%

Reduced sensitivity to reinforcement in adolescent compared to adult Sprague-Dawley rats of both sexes

Hankosky¹,

Westbrook²,

Haake³

et al. 2017

Preprint

View full text Add to dashboard Cite

RATIONALE: Adolescence is a period of considerable development of brain and behavior and is the time during which most drug use is initiated. OBJECTIVE: Age-dependent differences in motivated behaviors may be one of the factors that contribute to heightened vulnerability to developing substance use disorders, so we sought to compare age differences in methamphetamine (METH) and saccharin seeking. METHODS: Beginning during adolescence or adulthood, male and female Sprague-Dawley rats were trained to self-administer 0.1% saccharin (via liquid dipper cup) or intravenous METH at one of three doses (0.02, 0.05, 0.08 mg/kg/inf) under increasing fixed ratio schedules of reinforcement. Subsequently, responding for METH (0.02, 0.05, 0.08 or 0.1 mg/kg/inf) under progressive ratio response requirements was assessed in rats that acquired METH self-administration at the highest dose (0.08 mg/kg/inf). RESULTS:We found that adult-onset rats acquired METH self-administration more readily and exhibited higher motivation compared to adolescent-onset rats, although there were no differences in METH intake during acquisition. Adult rats also acquired saccharin selfadministration more readily, but in contrast to METH, there were age and sex differences in saccharin intake driven by high levels of responding in adult females. CONCLUSIONS: These findings challenge the prevailing notion that adolescents are hypersensitive to reward and instead raise questions about the potential role of methodological factors on which rodent studies often differ.

show abstract

“…However, this developmental change in synaptic plasticity cannot directly explain the observed learning deficit in BDNF +/2 mice, since the learning deficit should then already be present in 2-mo-old animals. Interestingly, the number of amygdala projection neurons, e.g., from the BLA to the prefrontal cortex, strongly increases during the first 90 d of development (Cunningham et al 2002(Cunningham et al , 2008, also …”

Section: Discussionmentioning

confidence: 97%

Age-dependent deficits in fear learning in heterozygous BDNF knock-out mice

Endres

Leßmann

2012

Learn. Mem.

View full text Add to dashboard Cite

Beyond its trophic function, the neurotrophin BDNF (brain-derived neurotrophic factor) is well known to crucially mediate synaptic plasticity and memory formation. Whereas recent studies suggested that acute BDNF/TrkB signaling regulates amygdala-dependent fear learning, no impairments of cued fear learning were reported in heterozygous BDNF knockout mice (BDNF +/2 ). Since brain BDNF levels are known to decline with aging, we hypothesized that BDNF +/2 mice might show reduced fear learning at older ages. Indeed, BDNF +/2 animals revealed an age-dependent deficit in fear learning 3 mo after birth and beyond. Since there were no alterations between the two genotypes during the conditioning training and when testing short-term memory, this learning deficit most likely reflects a deficit in memory consolidation. Importantly, there were no differences in spontaneous motor behavior and baseline anxiety in BDNF +/2 animals at any age tested. Following behavioral testing quantification of BDNF levels in the basolateral amygdala with a sensitive BDNF ELISA revealed a positive correlation between the levels of BDNF in the amygdala and the individual learning performance. However, the age-dependent decline in the efficiency of fear conditioning in BDNF +/2 mice was not accompanied by reduced BDNF expression in the amygdala. Thus, while reduced BDNF levels in general correlate with less efficient fear learning, this lack of BDNF can be compensated in young but not in older animals, suggesting that the cellular mechanisms responsible for fear learning consolidation become BDNF-dependent 3 mo after birth.

show abstract

Increasing Interaction of Amygdalar Afferents with GABAergic Interneurons between Birth and Adulthood

Cited by 85 publications

References 25 publications

Circuitry-based gene expression profiles in GABA cells of the trisynaptic pathway in schizophrenics versus bipolars

Circuitry-based gene expression profiles in GABA cells of the trisynaptic pathway in schizophrenics versus bipolars

Reduced sensitivity to reinforcement in adolescent compared to adult Sprague-Dawley rats of both sexes

Age-dependent deficits in fear learning in heterozygous BDNF knock-out mice

Contact Info

Product

Resources

About