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

Abstract

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 codistributed 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.

Bridging the gap between single receptor type activity and whole‐brain dynamics

“…That is, ongoing brain activity (reflecting state‐dependent whole‐brain internal communication processes) and activity evoked by sensory input (reflecting external drive). The results suggest indeed global whole‐brain changes in cortical state induced by 5‐HT input with balanced effects on internal ongoing activity and sensory drive [25,26]. Specifically, we find that 5‐HT1A scales predominantly the weight of internal communication, while 5‐HT2A largely scales the weight of external sensory input.…”

“…However, could the function of single 5-HT receptor types factually be attributed to distinct and separable effects on either sensory-evoked or internally ongoing activity as our whole-brain model implicates? To address this question experimentally, we used an ePet-Cre mouse line [27] that allowed controlled release of 5-HT by photostimulation of Channelrhodopsin2 expressing 5-HT neurons in the raphe nuclei [25,26]. In parallel we used optical imaging of Ca 2+ fluorescent indicators to track 5-HT-induced modulations of neuronal activity in the visual cortex in vivo (Fig.…”

Investigating the Serotonergic Modulation of Orientation Tuning of Neurons in Primary Visual Cortex of Anesthetized Mice

“…In our study, there also was not meaningful changes in mean membrane potential and mean firing rate of neurons' spontaneous activity before and during electrical stimulation of DRN, which is in agreement with some previous studies (Michaiel et al, 2019). In contrast, some studies reported decreased spontaneous activity in neuronal response by serotonin modulation (Azimi et al, 2018). It was suggested that decreasing gain might decrease the priority of a sensory stimulus (Seillier et al, 2017).…”

“…There is a large topographic organization in the dorsal raphe nucleus (Fiser et al, 2010), so other brain's cortical and subcortical areas are also modulated by serotonergic neuromodulatory neurons, affecting activity in the primary visual cortex (Azimi et al, 2018).…”

“…Perception and sensory cognition is the result of integrating two components (Michaiel et al, 2019). As, serotonergic system function may modulate cortical states and influence higher cognition functions such as decision and perception, long-term dysfunction of the serotonergic system may lead to psychiatric disorders including schizophrenia, depression and stress disorder (Azimi et al, 2018). Such studies can be helpful in diagnosis and treatment by providing new methods for rebalancing these components.…”