Please use this identifier to cite or link to this item: http://dr.iiserpune.ac.in:8080/xmlui/handle/123456789/8203
Title: Perceptual learning deficits mediated by somatostatin releasing inhibitory interneurons of olfactory bulb in an early life stress mouse model
Authors: PARDASANI, MEENAKSHI
RAMAKRISHNAN, ANANTHA MAHARASI
MAHAJAN, SARANG
KANTROO, MEHER
MCGOWAN, ELEANOR
DAS, SUSOBHAN
SRIKANTH, PRIYADHARSHINI
PANDEY, SANYUKTA
ABRAHAM, NIXON M.
Dept. of Biology
Keywords: Biological techniques
Depression
Neuroscience
2023-SEP-WEEK3
TOC-SEP-2023
2023
Issue Date: Sep-2023
Publisher: Springer Nature
Citation: Molecular Psychiatry, 28, 4693–4706
Abstract: Early life adversity (ELA) causes aberrant functioning of neural circuits affecting the health of an individual. While ELA-induced behavioural disorders resulting from sensory and cognitive disabilities can be assessed clinically, the neural mechanisms need to be probed using animal models by employing multi-pronged experimental approaches. As ELA can alter sensory perception, we investigated the effect of early weaning on murine olfaction. By implementing go/no-go odour discrimination paradigm, we observed olfactory learning and memory impairments in early life stressed (ELS) male mice. As olfactory bulb (OB) circuitry plays a critical role in odour learning, we studied the plausible changes in the OB of ELS mice. Lowered c-Fos activity in the external plexiform layer and a reduction in the number of dendritic processes of somatostatin-releasing, GABAergic interneurons (SOM-INs) in the ELS mice led us to hypothesise the underlying circuit. We recorded reduced synaptic inhibitory feedback on mitral/tufted (M/T) cells, in the OB slices from ELS mice, explaining the learning deficiency caused by compromised refinement of OB output. The reduction in synaptic inhibition was nullified by the photo-activation of ChR2-expressing SOM-INs in ELS mice. The role of SOM-INs was revealed by learning-dependent refinement of Ca2+dynamics quantified by GCaMP6f signals, which was absent in ELS mice. Further, the causal role of SOM-INs involving circuitry was investigated by optogenetic modulation during the odour discrimination learning. Photo-activating these neurons rescued the ELA-induced learning deficits. Conversely, photo-inhibition caused learning deficiency in control animals, while it completely abolished the learning in ELS mice, confirming the adverse effects mediated by SOM-INs. Our results thus establish the role of specific inhibitory circuit in pre-cortical sensory area in orchestrating ELA-dependent changes.
URI: https://doi.org/10.1038/s41380-023-02244-3
http://dr.iiserpune.ac.in:8080/xmlui/handle/123456789/8203
ISSN: 1476-5578
1359-4184
Appears in Collections:JOURNAL ARTICLES

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