Publications by authors named "Johannes Griessner"

4 Publications

  • Page 1 of 1

Central amygdala circuit dynamics underlying the benzodiazepine anxiolytic effect.

Mol Psychiatry 2021 02 30;26(2):534-544. Epub 2018 Nov 30.

Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Campus-Vienna-Biocenter 1, 1030, Vienna, Austria.

Benzodiazepines (BZDs) have been a standard treatment for anxiety disorders for decades, but the neuronal circuit interactions mediating their anxiolytic effect remain largely unknown. Here, we find that systemic BZDs modulate central amygdala (CEA) microcircuit activity to gate amygdala output. Combining connectome data with immediate early gene (IEG) activation maps, we identified the CEA as a primary site for diazepam (DZP) anxiolytic action. Deep brain calcium imaging revealed that brain-wide DZP interactions shifted neuronal activity in CEA microcircuits. Chemogenetic silencing showed that PKCδ/SST neurons in the lateral CEA (CEAl) are necessary and sufficient to induce the DZP anxiolytic effect. We propose that BZDs block the relay of aversive signals through the CEA, in part by local binding to CEAl SST/PKCδ neurons and reshaping intra-CEA circuit dynamics. This work delineates a strategy to identify biomedically relevant circuit interactions of clinical drugs and highlights the critical role for CEA circuitry in the pathophysiology of anxiety.
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http://dx.doi.org/10.1038/s41380-018-0310-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411154PMC
February 2021

Dorsal tegmental dopamine neurons gate associative learning of fear.

Nat Neurosci 2018 07 27;21(7):952-962. Epub 2018 Jun 27.

Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria.

Functional neuroanatomy of Pavlovian fear has identified neuronal circuits and synapses associating conditioned stimuli with aversive events. Hebbian plasticity within these networks requires additional reinforcement to store particularly salient experiences into long-term memory. Here we have identified a circuit that reciprocally connects the ventral periaqueductal gray and dorsal raphe region with the central amygdala and that gates fear learning. We found that ventral periaqueductal gray and dorsal raphe dopaminergic (vPdRD) neurons encode a positive prediction error in response to unpredicted shocks and may reshape intra-amygdala connectivity via a dopamine-dependent form of long-term potentiation. Negative feedback from the central amygdala to vPdRD neurons might limit reinforcement to events that have not been predicted. These findings add a new module to the midbrain dopaminergic circuit architecture underlying associative reinforcement learning and identify vPdRD neurons as a critical component of Pavlovian fear conditioning. We propose that dysregulation of vPdRD neuronal activity may contribute to fear-related psychiatric disorders.
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http://dx.doi.org/10.1038/s41593-018-0174-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6166775PMC
July 2018

Stress peptides sensitize fear circuitry to promote passive coping.

Mol Psychiatry 2020 02 14;25(2):428-441. Epub 2018 Jun 14.

Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Dr. Bohr Gasse 7, 1030, Vienna, Austria.

Survival relies on optimizing behavioral responses through experience. Animals often react to acute stress by switching to passive behavioral responses when coping with environmental challenge. Despite recent advances in dissecting mammalian circuitry for Pavlovian fear, the neuronal basis underlying this form of non-Pavlovian anxiety-related behavioral plasticity remains poorly understood. Here, we report that aversive experience recruits the posterior paraventricular thalamus (PVT) and corticotropin-releasing hormone (CRH) and sensitizes a Pavlovian fear circuit to promote passive responding. Site-specific lesions and optogenetic manipulations reveal that PVT-to-central amygdala (CE) projections activate anxiogenic neuronal populations in the CE that release local CRH in response to acute stress. CRH potentiates basolateral (BLA)-CE connectivity and antagonizes inhibitory gating of CE output, a mechanism linked to Pavlovian fear, to facilitate the switch from active to passive behavior. Thus, PVT-amygdala fear circuitry uses inhibitory gating in the CE as a shared dynamic motif, but relies on different cellular mechanisms (postsynaptic long-term potentiation vs. presynaptic facilitation), to multiplex active/passive response bias in Pavlovian and non-Pavlovian behavioral plasticity. These results establish a framework promoting stress-induced passive responding, which might contribute to passive emotional coping seen in human fear- and anxiety-related disorders.
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http://dx.doi.org/10.1038/s41380-018-0089-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169733PMC
February 2020

Virtual reality for freely moving animals.

Nat Methods 2017 Oct 21;14(10):995-1002. Epub 2017 Aug 21.

Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.

Standard animal behavior paradigms incompletely mimic nature and thus limit our understanding of behavior and brain function. Virtual reality (VR) can help, but it poses challenges. Typical VR systems require movement restrictions but disrupt sensorimotor experience, causing neuronal and behavioral alterations. We report the development of FreemoVR, a VR system for freely moving animals. We validate immersive VR for mice, flies, and zebrafish. FreemoVR allows instant, disruption-free environmental reconfigurations and interactions between real organisms and computer-controlled agents. Using the FreemoVR platform, we established a height-aversion assay in mice and studied visuomotor effects in Drosophila and zebrafish. Furthermore, by photorealistically mimicking zebrafish we discovered that effective social influence depends on a prospective leader balancing its internally preferred directional choice with social interaction. FreemoVR technology facilitates detailed investigations into neural function and behavior through the precise manipulation of sensorimotor feedback loops in unrestrained animals.
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http://dx.doi.org/10.1038/nmeth.4399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485657PMC
October 2017