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

INTRODUCTION: Sensory processing is profoundly regulated by brain neuromodulatory systems.

One of the main neuromodulators is serotonin which influences higher cognitive functions, such as different aspects of perceptual processing.

Accordingly, malfunction in the serotonergic system may lead to visual illusion in psychiatric disorders, such as autism and schizophrenia.

This study aims to investigate the serotonergic modulation of visual responses of neurons to stimulus orientation in the primary visual cortex.

METHODS: Eight-week-old naive mice were anesthetized and a craniotomy was done on the region of interest in the primary visual cortex.

Spontaneous and visual-evoked activities of neurons were recorded before and during the electrical stimulation of the dorsal raphe nucleus using in vivo whole-cell patch-clamp recording.

The square-wave grating of 12 orientations was presented.

The data were analyzed and the Wilcoxon signed-rank test was used to compare the data of two conditions that belong to the same neurons, with or without electrical stimulation.

RESULTS: The serotonergic system changed the orientation tuning of nearly 60% of recorded neurons by decreasing the mean firing rate in two independent visual response components, namely gain and baseline response.

It also increased the mean firing rate in a small number of neurons (about 20%).

Additionally, it left the preferred orientation and sensitivity of neurons unchanged.

CONCLUSION: Serotonergic modulation showed a bidirectional effect.

It causes predominately divisive and subtractive decreases in the visual responses of the neurons in the primary visual cortex that can modify the balance between internal and external sensory signals and result in disorders.

HIGHLIGHTS: The serotonergic system predominantly decreased the mean firing rate of neurons in the primary visual cortex.

The serotonergic system decreased responses of visual cortical neurons by subtractive and divisive changes of orientation tuning.

The serotonergic system leaves the spontaneous activity of visual cortical neurons unchanged.

PLAIN LANGUAGE SUMMARY: Serotonin is one of the well-known neuromodulators involved in many physiological functions of the brain, such as sensory processing.

It can play an essential role in producing perceptual psychotic episodes following the use of psychedelic drugs.

Neural mechanisms of changes in cortical processing by the serotonergic system are not elucidated enough.

In this study, we showed the electrical stimulation of the dorsal raphe nucleus as the main resource for projecting serotonergic neurons to the visual cortex, causing to decrease in visual-evoked responses of neurons in the primary visual cortex without changing the spontaneous activity.

This effect may lead to an imbalance between the brain’s intrinsic and stimulus-evoked activity and result in various kinds of psychiatric disorders, such as visual hallucinogenic experiences in schizophrenia and autism.

Accordingly, it is crucial to understand the mechanisms by which serotonin affects the rapid and long-term activity of neocortical circuits.

Such studies can be helpful in the diagnosis and treatment of disorders related to the neuromodulatory roles of the serotonergic system by providing new methods for rebalancing these intricate components.