Amygdala inputs to prefrontal cortex guide behavior amid conflicting cues of reward and punishment

Burgos-Robles, Anthony; Kimchi, Eyal Y.; Izadmehr, Ehsan M.; Porzenheim, Mary Jane; Ramos-Guasp, William A; Nieh, Edward H.; Felix-Ortiz, Ada C.; Namburi, Praneeth; Leppla, Christopher A.; Presbrey, Kara N.; Anandalingam, Kavitha; Pagan-Rivera, Pablo A; Anahtar, Melodi; Beyeler, Anna; Tye, Kay M.

doi:10.1038/nn.4553

Cited by 241 publications

(239 citation statements)

References 72 publications

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“…“Winner-take-all” effects have been observed in multisensory decision-making [8,9], while our summation model predicts that the influence of each modality should grow smoothly with intensity. To examine the effects of intensity, we presented real flies with single and multimodal stimuli at higher and lower wind speeds ( N = 11, 11, and 12 for wind at 10, 25, and 45 cm/s, respectively), while holding visual stimulus intensity constant.…”

Section: Resultsmentioning

confidence: 87%

Multisensory Control of Orientation in Tethered Flying Drosophila

Currier

Nagel

2018

Current Biology

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Summary A longstanding goal of systems neuroscience is to quantitatively describe how the brain integrates sensory cues over time. Here we develop a closed-loop orienting paradigm in Drosophila to study the algorithms by which cues from two modalities are integrated during ongoing behavior. We find that flies exhibit two behaviors when presented simultaneously with an attractive visual stripe and aversive wind cue. First, flies perform a turn sequence where they initially turn away from the wind and but later turn back toward the stripe, suggesting dynamic sensory processing. Second, turns toward the stripe are slowed by the presence of competing wind, suggesting summation of turning drives. We develop a model in which signals each modality are filtered in space and time to generate turn commands, then summed to produce ongoing orienting behavior. This computational framework correctly predicts behavioral dynamics for a range of stimulus intensities and spatial arrangements.

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Section: Resultsmentioning

confidence: 87%

Multisensory Control of Orientation in Tethered Flying Drosophila

Currier

Nagel

2018

Current Biology

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“…To directly test the hypothesis that socially-derived information about the aversive cue is transmitted from the ACC to the BLA during observational conditioning, we used an intersectional viral strategy (Senn et al, 2014) to express Channelrhodopsin-2 (ChR2) in ACC neurons that monosynaptically project to the BLA (Figure 4A–B) (Burgos-Robles et al, 2017). Ex vivo recordings demonstrated that ChR2-expressing neurons fired action potentials in response to blue light while non-expressing neighbors showed no response (Figure 4C).…”

Section: Resultsmentioning

confidence: 99%

Corticoamygdala Transfer of Socially Derived Information Gates Observational Learning

Allsop

Wichmann

Mills

et al. 2018

Cell

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218

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Observational learning is a powerful survival tool allowing individuals to learn about threat-predictive stimuli without directly experiencing the pairing of the predictive cue and punishment. This ability has been linked to the anterior cingulate cortex (ACC) and the basolateral amygdala (BLA). To investigate how information is encoded and transmitted through this circuit, we performed electrophysiological recordings in mice observing a demonstrator mouse undergo associative fear conditioning and found that BLA-projecting ACC (ACC→BLA) neurons preferentially encode socially derived aversive cue information. Inhibition of ACC→BLA alters real-time amygdala representation of the aversive cue during observational conditioning. Selective inhibition of the ACC→BLA projection impaired acquisition, but not expression, of observational fear conditioning. We show that information derived from observation about the aversive value of the cue is transmitted from the ACC to the BLA and that this routing of information is critically instructive for observational fear conditioning. VIDEO ABSTRACT.

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“…For example, Burgos‐Robles et al . () inhibited the projection from the basolateral amygdala to the prelimbic cortex using a combination of CAV and the human M 4 (hM4Di) DREADD to demonstrate a functional role for this pathway in fear‐associated memories. The AAV serotype 2/5 has also been shown to have retrograde tropism (Aschauer et al ., ).…”

Section: Viral Methods For Chemogenetic Receptor Expressionmentioning

confidence: 99%

The use of chemogenetics in behavioural neuroscience: receptor variants, targeting approaches and caveats

Campbell

Marchant

2018

British J Pharmacology

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The last decade has seen major advances in neuroscience tools allowing us to selectively modulate cellular pathways in freely moving animals. Chemogenetic approaches such as designer receptors exclusively activated by designer drugs (DREADDs) permit the remote control of neuronal function by systemic drug administration. These approaches have dramatically advanced our understanding of the neural control of behaviour. Here, we review the different techniques and genetic approaches available for the restriction of chemogenetic receptors to defined neuronal populations. We highlight the use of a dual virus approach to target specific circuitries and the effectiveness of different routes of administration of designer drugs. Finally, we discuss the potential caveats associated with DREADDs including off-target effects of designer drugs, the effects of chronic chemogenetic receptor activation and the issue of collateral projections associated with DREADD activation and inhibition. AbbreviationsAAVs, adeno-associated viral vectors; BBB, blood-brain barrier; CAMKII, calmodulin-dependent protein kinase II; CAVs, canine adenoviruses; CNO, clozapine N-oxide; DREADDs, designer receptors exclusively activated by designer drugs; hM3D, human M 3 muscarinic DREADD; hM4D, human M 4 muscarinic DREADD; HSV, herpes simplex viral; hSyn, human synapsin; KORD, κ-opioid-based receptor designer receptor exclusively activated by designer drugs; LGICs, ligand-gated ion channels; NAc, nucleus accumbens; RASSL, receptor activated solely by a synthetic ligand; SalB, salvinorin B; VTA, ventral tegmental area IntroductionDuring the last decade, there has been a revolution in neuroscience techniques that have resulted in increasingly precise methods to manipulate neural systems in awake, behaving animals. Understanding the relationship between brain function and behaviour is critical for the advancement of both neuroscience research and targeted medication development. Chemogenetics refers to the technique that allows for the reversible remote control of cell populations and neural circuitry via systemic injection or microinfusion of an activating ligand (Alexander et al., 2009;Armbruster et al., 2007). The chemogenetic technique uses engineered receptors and biologically inert ligands to achieve this aim. Unlike optogenetics, which has the ability to control cells and neural circuitry with light, the use of designer drugs makes chemogenetics simple to use, removing the need for optical fibre probes and tethers. While the temporal resolution of chemogenetics is lower than optogenetics, this relatively non-invasive technique is still effective for functional mapping, cell-type-specific manipulations and multiplexed control of neurons.In this review, we will evaluate the different strategies that have been used to restrict chemogenetic receptors to defined neuronal populations. We will also highlight the use of a dual virus approach at targeting projection neurons and the effectiveness of different routes of administration of designer drugs. Fin...

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Amygdala inputs to prefrontal cortex guide behavior amid conflicting cues of reward and punishment

Cited by 241 publications

References 72 publications

Multisensory Control of Orientation in Tethered Flying Drosophila

Multisensory Control of Orientation in Tethered Flying Drosophila

Corticoamygdala Transfer of Socially Derived Information Gates Observational Learning

The use of chemogenetics in behavioural neuroscience: receptor variants, targeting approaches and caveats

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