Information capacity and robustness of encoding in the medial prefrontal cortex are modulated by the bioavailability of serotonin and the time elapsed from the cue during a reward-driven task

A Ezequiel Pereyra,Camilo J Mininni,B Silvano Zanutto

doi:10.1038/s41598-021-93313-6

Abstract

Serotonin (5-HT) is a key neuromodulator of medial prefrontal cortex (mPFC) functions. Pharmacological manipulation of systemic 5-HT bioavailability alters the electrical activity of mPFC neurons. However, 5-HT modulation at the population level is not well characterized. In the present study, we made single neuron extracellular recordings in the mPFC of rats performing an operant conditioning task, and analyzed the effect of systemic administration of fluoxetine (a selective serotonin reuptake inhibitor) on the information encoded in the firing activity of the neural population. Chronic (longer than 15 days), but not acute (less than 15 days), fluoxetine administration reduced the firing rate of mPFC neurons. Moreover, fluoxetine treatment enhanced pairwise entropy but diminished noise correlation and redundancy in the information encoded, thus showing how mPFC differentially encodes information as a function of 5-HT bioavailability. Information about the occurrence of the reward-predictive stimulus was maximized during reward consumption, around 3 to 4 s after the presentation of the cue, and it was higher under chronic fluoxetine treatment. However, the encoded information was less robust to noise corruption when compared to control conditions.

Highlights

Serotonin (5-HT) is a key neuromodulator of medial prefrontal cortex functions
The inhibition of medial prefrontal cortex (mPFC) neuronal activity after administration of fluoxetine is consistent with previous studies carried out on anesthetized r ats[32, 33]
The mPFC has a critical role in the execution of goal-directed behaviours

Summary

Introduction

Serotonin (5-HT) is a key neuromodulator of medial prefrontal cortex (mPFC) functions. We made single neuron extracellular recordings in the mPFC of rats performing an operant conditioning task, and analyzed the effect of systemic administration of fluoxetine (a selective serotonin reuptake inhibitor) on the information encoded in the firing activity of the neural population. Firing rate profile of neural population recordings in mPFC of behaving rats executing an operant conditioning task. The auditory cue (tone) was presented for 1 s (yellow bar), followed by an opportunity window of 2 s, in which the rat had to execute the conditioned response (lick) to obtain a drop of water as reward, otherwise the reward was omitted Both situations were followed by a fixed inter-trial time interval of 10 s. MPFC neurons encode reward-related signals and are strongly modulated by 5-HT, there is a lack of studies characterizing its modulation at the circuit level in behaving animals, as well as its involvement in encoding reward-related s timuli[21]

Methods

Results

Conclusion