Perceptual learning deficits mediated by somatostatin releasing inhibitory interneurons of olfactory bulb in an early life stress mouse model

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.

Long COVID: From olfactory dysfunctions to viral Parkinsonism

“…Clinical reports investigating various aspects of brain pathophysiology provide the potential link between Parkinson's disease and viral infections, including SARS‐CoV‐2. However, to move toward the causality and circuit mechanisms, a multipronged experimental approach using animal models is needed 124–129 . Different animal models that can be used to predict adverse effects of long‐COVID 82,127,130 .…”

Parvalbumin interneuron ErbB4 controls ongoing network oscillations and olfactory behaviors in mice

“…Interglomerular lateral inhibition sharpens or filters the odor-induced output signals of MCs, enhancing the contrast of odor representations and consequently the ability to discriminate similar odors (Egger and Kuner, 2021). Overall, the OB possesses various types of interneurons to control different olfactory behaviors (Lyons-Warren et al, 2023;Pardasani et al, 2023;Takahashi et al, 2016). Parvalbumin-positive (PV) interneurons form dendrodendritic contacts with the somata and dendrites of neighboring MCs ( Huang et al, 2013;Kato et al, 2013;Matsuno et al, 2017;Miyamichi et al, 2013).…”