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Hippocampal OLMα2 cells gate basolateral amygdala inputs for threat processing
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Kullander: Formation and Function of Neuronal Circuits.
Brain Institute, Federal University of Rio Grande do Norte, Natal - Brazil.. (Neurodynamics)
Brain Institute, Federal University of Rio Grande do Norte, Natal - Brazil.. (Computational Neurophysiology)
Departamento de Engenharia Biomedica, Natal, Brazil.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

It is becoming increasingly clear that the hippocampus is functionally diverse across its longitudinal axis. The ventral hippocampus is known to participate anxiety-related behaviors and may, together with the basolateral amygdala (BLA), facilitate threat aversion. Nevertheless, studies of mechanisms and circuit organization for processing value related cues are scarce. Here we investigate a microcircuit involving a subgroup of interneurons, referred to as Oriens lacunosum-moleculare cells, defined by their expression of the nicotinic receptor alpha2 subunit (OLMα2). Such cells can bidirectionally affect the response to predator odor as well as the encoding of object memories. In tracing experiments, we found that the basolateral amygdala mainly projects to the ventral hippocampus, whereas the medial amygdala and claustrum projects to the intermediate hippocampus. Moreover, we found that BLA inputs inhibit intrinsic hippocampal slow oscillation.  Optogenetic stimulation of OLMα2 cells in the intermediate hippocampus caused an increase in approach of objects. Inhibition of ventrally located OLMα2 cells cause an increased avoidance to natural aversive stimuli and could entrain aversion to value neutral odors. In contrast, theta II oscillations, which predominantly appear in the ventral hippocampus during anxiety related behaviors, were absent during object recognition. Theta II oscillations only appeared when the animal was naïve to the arena setting. We conclude that there are functional differences between the intermediate and ventral hippocampus and that OLMα2 cells, in addition to sensory inputs, process emotional value signals from the amygdala. 

National Category
Neurosciences
Research subject
Neuroscience
Identifiers
URN: urn:nbn:se:uu:diva-439658OAI: oai:DiVA.org:uu-439658DiVA, id: diva2:1542879
Available from: 2021-04-08 Created: 2021-04-08 Last updated: 2021-04-08
In thesis
1. Hippocampal circuit dynamics in learning and value processing of sensory cues: A study into the function of hippocampal microcircuits involving OLMα2 cells
Open this publication in new window or tab >>Hippocampal circuit dynamics in learning and value processing of sensory cues: A study into the function of hippocampal microcircuits involving OLMα2 cells
2021 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The anatomical signatures of the mnemonic/emotional processes share many brain structures, one of which seems to constitute a bridge, the hippocampus. It functions as a structure that consolidates engrams. It is connected to the prefrontal cortex, nucleus accumbens and amygdala, structures that provide emotional salience. This is, from an evolutionary perspective, likely a selection of fitness relevant engrams. Inputs from such structures to the hippocampus increase the likelihood of engram consolidation and behavioral response into long-term deposits. The hippocampal input pathways appear to be of importance for encoding and retrieval processes. During first encounters, entorhinal temporoammonic inputs are necessary for identifying probable threats and encoding of environmental cues. We find that artificial silencing of gate keeper neurons, named oriens lacunosum-moleculare (OLM) cells, increases approach and memory recall of novel cues in several tasks. Further, silencing of OLM cells mediates effective learning by increasing promiscuity in pyramidal cells in response to incoming sensory and/or emotional value inputs from other limbic structures, such as the basolateral amygdala. Depending on the dorsoventral position of the OLM cells, different phenotypes can be observed in different tasks. This is likely, at least in part, because of dorso-ventral differences in the connections between the hippocampus and other structures. In addition, OLM cells can control the specific oscillation frequency theta II (6-8 Hz), which appears in the ventral hippocampus and facilitates approach to predator odors. In conclusion, we show that the hippocampal circuit involving a subtype of OLM cells, is processing value of sensory cues through the temporoammonic pathway, and possibly affecting the basolateral amygdala inputs.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2021. p. 49
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1743
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-439659 (URN)978-91-513-1188-3 (ISBN)
Public defence
2021-06-01, On Zoom, Uppsala, 14:00 (English)
Opponent
Supervisors
Available from: 2021-05-07 Created: 2021-04-08 Last updated: 2021-05-25

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Siwani, SamerLeão, Richardson NKullander, Klas

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Kullander: Formation and Function of Neuronal CircuitsDepartment of NeuroscienceScience for Life Laboratory, SciLifeLabDepartment of Medical Cell Biology
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