GABAA Receptors Containing Gamma1 Subunits Contribute to Inhibitory Transmission in the Central Amygdala

2009 ◽  
Vol 101 (1) ◽  
pp. 341-349 ◽  
Author(s):  
Abolghasem Esmaeili ◽  
Joseph W. Lynch ◽  
Pankaj Sah
Keyword(s):  
Gaba Receptors ◽  
Basolateral Amygdala ◽  
Conditioned Fear ◽  
Subunit Composition ◽  
Hek293 Cells ◽  
Mammalian Brain ◽  
Central Amygdala ◽  
Bed Nucleus ◽  
Gabaergic Synapses ◽  
Inhibitory Transmitter

γ-Aminobutyric acid (GABA) is the primary inhibitory transmitter in the mammalian brain. This inhibition is mediated by type A (GABAA) receptors that are pentameric proteins assembled from 14 different subunits. Although inhibitory synaptic transmission has been studied in the amygdala, the subunit composition of receptors present at different synapses is not well understood. In this study we examined the subunit composition of GABAA receptors at synapses in the basolateral and central amygdala. Using receptors expressed in HEK293 cells we first determined the pharmacology of receptors of different subunit compositions. We then used this pharmacological profile to test the properties of receptors present at synapses in the central and basolateral amygdala. These results show that the GABAA receptor subunits are differentially distributed in the amygdala. Our data indicate that in the basolateral amygdala, GABAergic synapses are likely composed of receptors that contain α2βxγ2 subunits. In the central amygdala receptors at the medial input, carrying afferents from the bed nucleus of the stria terminalis contain similar receptors, whereas in the lateral input GABA receptors likely contain γ1 subunits. These inputs arise from the intercalated cells masses, thought to be responsible for mediating extinction of conditioned fear, raising the possibility of new targets for the treatment of anxiety-related disorders.

scholarly journals Timing of Impulses From the Central Amygdala and Bed Nucleus of the Stria Terminalis to the Brain Stem

2008 ◽  
Vol 100 (6) ◽  
pp. 3429-3436 ◽  
Author(s):  
Frank Z. Nagy ◽  
Denis Paré
Keyword(s):  
Brain Stem ◽  
Basolateral Amygdala ◽  
Stria Terminalis ◽  
Central Amygdala ◽  
Response Latencies ◽  
Bed Nucleus ◽  
Antidromic Responses ◽  
The Brain ◽  
Antidromic Response ◽  
Shed Light

The amygdala and bed nucleus of the stria terminalis (BNST) are thought to subserve distinct functions, with the former mediating rapid fear responses to discrete sensory cues and the latter longer “anxiety-like” states in response to diffuse environmental contingencies. However, these structures are reciprocally connected and their projection sites overlap extensively. To shed light on the significance of BNST–amygdala connections, we compared the antidromic response latencies of BNST and central amygdala (CE) neurons to brain stem stimulation. Whereas the frequency distribution of latencies was unimodal in BNST neurons (∼10-ms mode), that of CE neurons was bimodal (∼10- and ∼30-ms modes). However, after stria terminalis (ST) lesions, only short-latency antidromic responses were observed, suggesting that CE axons with long conduction times course through the ST. Compared with the direct route, the ST greatly lengthens the path of CE axons to the brain stem, an apparently disadvantageous arrangement. Because BNST and CE share major excitatory basolateral amygdala (BL) inputs, lengthening the path of CE axons might allow synchronization of BNST and CE impulses to brain stem when activated by BL. To test this, we applied electrical BL stimuli and compared orthodromic response latencies in CE and BNST neurons. The latency difference between CE and BNST neurons to BL stimuli approximated that seen between the antidromic responses of BNST cells and CE neurons with long conduction times. These results point to a hitherto unsuspected level of temporal coordination between the inputs and outputs of CE and BNST neurons, supporting the idea of shared functions.

scholarly journals Photopotentiation of the GABAA receptor with caged diazepam

2019 ◽  
Vol 116 (42) ◽  
pp. 21176-21184 ◽  
Author(s):  
Lorenzo Sansalone ◽  
Joshua Bratsch-Prince ◽  
Sicheng Tang ◽  
Burjor Captain ◽  
David D. Mott ◽  
...  
Keyword(s):  
Gaba Receptors ◽  
Basolateral Amygdala ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Gaba Release ◽  
Intrinsic Activity ◽  
Gabaergic Synapses ◽  
The Central Nervous System ◽  
Complementary Nature ◽  
Inhibitory Signaling

As the inhibitory γ-aminobutyric acid–ergic (GABAergic) transmission has a pivotal role in the central nervous system (CNS) and defective forms of its synapses are associated with serious neurological disorders, numerous versions of caged GABA and, more recently, photoswitchable ligands have been developed to investigate such transmission. While the complementary nature of these probes is evident, the mechanisms by which the GABA receptors can be photocontrolled have not been fully exploited. In fact, the ultimate need for specificity is critical for the proper synaptic exploration. No caged allosteric modulators of the GABAA receptor have been reported so far; to introduce such an investigational approach, we exploited the structural motifs of the benzodiazepinic scaffold to develop a photocaged version of diazepam (CD) that was tested on basolateral amygdala (BLa) pyramidal cells in mouse brain slices. CD is devoid of any intrinsic activity toward the GABAA receptor before irradiation. Importantly, CD is a photoreleasable GABAA receptor-positive allosteric modulator that offers a different probing mechanism compared to caged GABA and photoswitchable ligands. CD potentiates the inhibitory signaling by prolonging the decay time of postsynaptic GABAergic currents upon photoactivation. Additionally, no effect on presynaptic GABA release was recorded. We developed a photochemical technology to individually study the GABAA receptor, which specifically expands the toolbox available to study GABAergic synapses.

Opposing Influence of Basolateral Amygdala and Footshock Stimulation on Neurons of the Central Amygdala

2006 ◽  
Vol 59 (9) ◽  
pp. 801-811 ◽  
Author(s):  
J. Amiel Rosenkranz ◽  
Deanne M. Buffalari ◽  
Anthony A. Grace
Keyword(s):  
Basolateral Amygdala ◽  
Central Amygdala

scholarly journals The transition from memory retrieval to extinction

2004 ◽  
Vol 76 (3) ◽  
pp. 573-582 ◽  
Author(s):  
Martín Cammarota ◽  
Daniela M. Barros ◽  
Mónica R.M. Vianna ◽  
Lia R.M. Bevilaqua ◽  
Adriana Coitinho ◽  
...  
Keyword(s):  
Basolateral Amygdala ◽  
Conditioned Fear ◽  
Test Session ◽  
Protein Synthesis Inhibitors ◽  
Molecular Systems ◽  
Safe Area ◽  
The Us ◽  
New Learning ◽  
The Moment ◽  
Training Apparatus

Memory is measured by measuring retrieval. Retrieval is often triggered by the conditioned stimulus (CS); however, as known since Pavlov, presentation of the CS alone generates extinction. One-trial avoidance (IA) is a much used conditioned fear paradigm in which the CS is the safe part of a training apparatus, the unconditioned stimulus (US) is a footshock and the conditioned response is to stay in the safe area. In IA, retrieval is measured without the US, as latency to step-down from the safe area (i.e., a platform). Extinction is installed at the moment of the first unreinforced test session, as clearly shown by the fact that many drugs, including PKA, ERK and protein synthesis inhibitors as well as NMDA receptor antagonists, hinder extinction when infused into the hippocampus or the basolateral amygdala at the moment of the first test session but not later. Some, but not all the molecular systems required for extinction are also activated by retrieval, further endorsing the hypothesis that although retrieval is behaviorally and biochemically necessary for the generation of extinction, this last process constitutes a new learning secondary to the unreinforced expression of the original trace.

scholarly journals Dopamine D2 receptor-mediated circuit from the central amygdala to the bed nucleus of the stria terminalis regulates impulsive behavior

2018 ◽  
Vol 115 (45) ◽  
pp. E10730-E10739 ◽  
Author(s):  
Bokyeong Kim ◽  
Sehyoun Yoon ◽  
Ryuichi Nakajima ◽  
Hyo Jin Lee ◽  
Hee Jeong Lim ◽  
...  
Keyword(s):  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Inhibitory Neurons ◽  
Stria Terminalis ◽  
Neural Pathways ◽  
Impulsive Behavior ◽  
Central Amygdala ◽  
Dopamine System ◽  
Addictive Disorders ◽  
Bed Nucleus

Impulsivity is closely associated with addictive disorders, and changes in the brain dopamine system have been proposed to affect impulse control in reward-related behaviors. However, the central neural pathways through which the dopamine system controls impulsive behavior are still unclear. We found that the absence of the D2 dopamine receptor (D2R) increased impulsive behavior in mice, whereas restoration of D2R expression specifically in the central amygdala (CeA) of D2R knockout mice (Drd2−/−)normalized their enhanced impulsivity. Inhibitory synaptic output from D2R-expressing neurons in the CeA underlies modulation of impulsive behavior because optogenetic activation of D2R-positive inhibitory neurons that project from the CeA to the bed nucleus of the stria terminalis (BNST) attenuate such behavior. Our identification of the key contribution of D2R-expressing neurons in the CeA → BNST circuit to the control of impulsive behavior reveals a pathway that could serve as a target for approaches to the management of neuropsychiatric disorders associated with impulsivity.

scholarly journals Separable Dorsal Raphe Dopamine Projections Mediate Sociability and Valence

2021 ◽  
Author(s):  
Kay Tye ◽  
Gillian Matthews ◽  
Mackenzie Lemieux ◽  
Elizabeth Brewer ◽  
Raymundo Miranda ◽  
...  
Keyword(s):  
Basolateral Amygdala ◽  
Ex Vivo ◽  
Affective State ◽  
Well Being ◽  
Dorsal Raphe ◽  
Receptor Expression ◽  
Dopamine Neurons ◽  
Bed Nucleus ◽  
Distributed Target ◽  
Dorsal Raphé

Abstract Affiliative social connections facilitate well-being and survival in numerous species. Engaging in social interactions requires positive and negative motivational drive, elicited through coordinated activity across neural circuits. However, the identity, interconnectivity, and functional encoding of social information within these circuits remains poorly understood. Here, we focused on downstream projections of dorsal raphe nucleus (DRN) dopamine neurons (DRNDAT), which we previously implicated in ‘negative drive’-induced social motivation. We show that three prominent DRNDAT projections – to the bed nucleus of the stria terminalis (BNST), central amygdala (CeA), and posterior basolateral amygdala (BLP) – play separable roles in behavior, despite substantial collateralization. Photoactivation of the DRNDAT-CeA projection promoted social behavior and photoactivation of the DRNDAT-BNST projection promoted exploratory behavior, while the DRNDAT-BLP projection supported place avoidance, suggesting a negative affective state. Downstream regions showed diverse, region-specific, receptor expression, poising DRNDAT neurons to act through dopamine, neuropeptide, and glutamate transmission. Furthermore, we show ex vivo that the effect of DRNDAT photostimulation on downstream neuron excitability was predicted by baseline cell properties, suggesting cell-type-specific modulation. Collectively, these data indicate that DRNDAT neurons may bias behavior via precise modulation of cellular activity in broadly-distributed target structures.

scholarly journals Basolateral and central amygdala orchestrate how we learn whom to trust

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Ronald Sladky ◽  
Federica Riva ◽  
Lisa Anna Rosenberger ◽  
Jack van Honk ◽  
Claus Lamm
Keyword(s):  
Nucleus Accumbens ◽  
Choice Behavior ◽  
Basolateral Amygdala ◽  
Outcome Evaluation ◽  
Reward Processing ◽  
Trust Game ◽  
Central Amygdala ◽  
Learning Success ◽  
Fmri Study ◽  
Human Neuroimaging

AbstractCooperation and mutual trust are essential in our society, yet not everybody is trustworthy. In this fMRI study, 62 healthy volunteers performed a repeated trust game, placing trust in a trustworthy or an untrustworthy player. We found that the central amygdala was active during trust behavior planning while the basolateral amygdala was active during outcome evaluation. When planning the trust behavior, central and basolateral amygdala activation was stronger for the untrustworthy player compared to the trustworthy player but only in participants who actually learned to differentiate the trustworthiness of the players. Independent of learning success, nucleus accumbens encoded whether trust was reciprocated. This suggests that learning whom to trust is not related to reward processing in the nucleus accumbens, but rather to engagement of the amygdala. Our study overcomes major empirical gaps between animal models and human neuroimaging and shows how different subnuclei of the amygdala and connected areas orchestrate learning to form different subjective trustworthiness beliefs about others and guide trust choice behavior.

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