Serotonin Decreases the Gain of Visual Responses in Awake Macaque V1

Abstract

Serotonin, an important neuromodulator in the brain, is implicated in affective and cognitive functions. However, its role even for basic cortical processes is controversial. For example, in the mammalian primary visual cortex (V1), heterogenous serotonergic modulation has been observed in anesthetized animals. Here, we combined extracellular single-unit recordings with iontophoresis in awake animals. We examined the role of serotonin on well-defined tuning properties (orientation, spatial frequency, contrast, and size) in V1 of two male macaque monkeys. We find that in the awake macaque the modulatory effect of serotonin is surprisingly uniform: it causes a mainly multiplicative decrease of the visual responses and a slight increase in the stimulus-selective response latency. Moreover, serotonin neither systematically changes the selectivity or variability of the response, nor the interneuronal correlation unexplained by the stimulus (“noise-correlation”). The modulation by serotonin has qualitative similarities with that for a decrease in stimulus contrast, but differs quantitatively from decreasing contrast. It can be captured by a simple additive change to a threshold-linear spiking nonlinearity. Together, our results show that serotonin is well suited to control the response gain of neurons in V1 depending on the animal's behavioral or motivational context, complementing other known state-dependent gain-control mechanisms.SIGNIFICANCE STATEMENT Serotonin is an important neuromodulator in the brain and a major target for drugs used to treat psychiatric disorders. Nonetheless, surprisingly little is known about how it shapes information processing in sensory areas. Here we examined the serotonergic modulation of visual processing in the primary visual cortex of awake behaving macaque monkeys. We found that serotonin mainly decreased the gain of the visual responses, without systematically changing their selectivity, variability, or covariability. This identifies a simple computational function of serotonin for state-dependent sensory processing, depending on the animal's affective or motivational state.

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

“…Finally, a previous study in monkey V1, using single cell recordings and pharmacological 5-HT1B and 5-HT2A receptor activation via microiontophoresis in anaesthetized preparations, revealed effects on both spontaneous activity and response gain (Shimegi et al, 2016). In contrast to ours and the above study, where the additional subtractive component essentially contributed to contrastgain control at lower contrast, a more recent study in monkey V1 found, however, for the majority of recorded cells only divisive scaling of evoked responses (Seillier et al, 2017). As their recordings were done in awake monkeys, these differences may indeed reflect principal changes in cortical state and 5-HT levels during wakefulness (Portas et al, 2000;Tyree et al, 2017) and/or species-specific differences in individual 5-HT receptor sets ("receptomes") tailored to task-specific demands on signal integration.…”

“…In addition, direct cortical application of 5-HT via microiontophoresis and single cell cortical recordings in vivo showed either suppressive or facilitative effects (Krnjevic and Phillis, 1963;Reader, 1978;Waterhouse et al, 1990). More recent studies applied antagonist and agonist of 5-HT via microiontophoresis in the monkey visual cortex, suggesting that 5hydroxytryptamin (5-HT)-receptors are involved in normalization of visual responses (Watakabe et al, 2009;Seillier et al, 2017). However, so far, only studies on somatosensorydriven behavioral responses (Dugué et al, 2014) and in olfactory cortex (Lottem et al, 2016) specifically activated 5-HT neurons in the DRN to trigger the natural and intrinsic spatiotemporal synaptic 5-HT innervation pattern within the target cortical areas.…”

Serotonin improves behavioral contrast sensitivity of freely moving rats

“…Hz) during awakening [8,9] to maintain the arousal state by acting on the hypothalamus [10,11] and cerebral cortex [12,13]. Serotonergic neurons project to the cerebral cortex including visual areas [14][15][16] and are known to modulate neuronal visual responses via various kinds of 5-HT receptor subtypes [17][18][19][20]. For example, Waterhouse et al (1990) reported that iontophoretically-administered serotonin decreases the signal-to-noise ratio of the neuronal activities in the primary visual cortex (V1) of anesthetized rats [17].…”

An investigation into serotonergic and environmental interventions against depression in a simulated delayed reward paradigm

“…While 5HTR1 is inhibitory, 5HTR2 is excitatory. Recent findings point to a more sophisticated role of these receptors when investigating response curves of cortical processing as done in the visual cortex (Shimegi et al, 2016;Seillier et al, 2017) and we propose that 5HT alters the signal processing in the mPFC in a similar way.…”