Biology subjects

Spoida, K.

Publications and source records attributed to Spoida, K..

3 recordsLinked to original sources

bioRxiv2025

Constitutive activity of the inhibitory G protein pathway mediated by non-visual opsin Opn7b reduces cFos activity in stress and fear circuits and modulates avoidance behavior

Constitutive activity of G protein-coupled receptors (GPCRs) plays an important role in brain function and disease including neurodegenerative and psychiatric disorders. The non-visual opsin Opn7b is a constitutively active Gi/o coupled GPCR which has been used to synchronize neuronal networks. Here we show that expression of Opn7b in the bed nucleus of the stria terminalis and the ventral tegmental area, two interconnected brain areas involved in modulating fear and stress responses, reduces the number of cFos positive neurons and modulates avoidance behavior in mice. Thus, by constitutively activating the Gi/o pathway Opn7b can be used as a tool to reduce cFos expression and to link cFos-expressing neurons to network- and pathway-specific behavior.

neuroscience↗

bioRxiv2022

Constitutive 5-HT2C receptor knock-out facilitates fear extinction through altered activity of a dorsal raphe-bed nucleus of the stria terminalis pathway

Serotonin 2C receptors (5-HT2CRs) are widely distributed throughout the brain and are strongly implicated in the pathophysiology of anxiety disorders such as post-traumatic stress disorder (PTSD). Although in recent years, a considerable amount of evidence supports 5-HT2CRs facilitating effect on anxiety behavior, the involvement in learned fear responses and fear extinction is rather unexplored. Here we used a 5-HT2CR knock-out mouse line (2CKO) to gain new insights into the involvement of 5-HT2CRs in the neuronal fear circuitry. Using a cued fear conditioning paradigm, our results revealed that global loss of 5-HT2CRs exclusively accelerates fear extinction, without affecting fear acquisition and fear expression. To investigate the neuronal substrates underlying the extinction enhancing effect, we mapped the immediate-early gene product cFos, a marker for neuronal activity, in the dorsal raphe nucleus (DRN), amygdala and bed nucleus of the stria terminalis (BNST). Surprisingly, besides extinction-associated changes, our results revealed alterations in neuronal activity even under basal home cage conditions in specific subregions of the DRN and the BNST in 2CKO mice. Neuronal activity in the dorsal BNST was shifted in an extinction-supporting direction due to 5-HT2CR knock-out. Finally, the assessment of DRN-BNST connectivity using antero- and retrograde tracing techniques uncovered a discrete serotonergic DRC-BNSTad pathway showing increased activity in 2CKO mice. Thus, our results provide new insights for the fear extinction network by revealing a specific serotonergic DRC-BNSTad pathway underlying a 5-HT2CR-sensitive mechanism with high significance in the treatment of PTSD.

neuroscience↗

bioRxiv2018

Subtraction and division of visual cortical population responses by the serotonergic system

Normalization is a fundamental operation throughout neuronal systems to adjust dynamic range. In the visual cortex various cell circuits have been identified that provide the substrate for such a canonical function, but how these circuits are orchestrated remains unclear. Here we suggest the serotonergic (5-HT) system as another player involved in normalization. 5-HT receptors of different classes are co-distributed across different cortical cell types, but their individual contribution to cortical population responses is unknown. We combined wide-field calcium imaging of primary visual cortex (V1) with optogenetic stimulation of 5-HT neurons in mice dorsal raphe nucleus (DRN) -- the major hub for widespread release of serotonin across cortex -- in combination with selective 5-HT receptor blockers. While inhibitory (5-HT1A) receptors accounted for subtractive suppression of spontaneous activity, depolarizing (5-HT2A) receptors promoted divisive suppression of response gain. Added linearly, these components led to normalization of population responses over a range of visual contrasts.

neuroscience↗