ANTAGONISTIC GATING OF CORTICAL CIRCUITS BY SEROTONIN AND ACETYLCHOLINE

Sensory perception depends on coordinated feedforward and feedback pathways linking sensory organs, primary sensory cortex and higher cortical areas. In the visual system, feedforward circuits convey direct information from the environment, whereas feedback circuits provide indirect contextual information from the surround to predict incoming sensory input. Neuromodulatory systems are ideally positioned to flexibly shape these interactions, adjusting cortical processing according to behavioral state and context. However, how these neuromodulatory systems dynamically regulate feedforward and feedback pathways remains unclear.
In this study, we investigated how serotonergic neurons in the dorsal raphe nucleus and cholinergic neurons in the basal forebrain nucleus basalis differentially modulate visual processing in the mouse visual cortex. We quantified the effect of optogenetic stimulation of cholinergic or serotonergic input on feedforward and feedback processing. Acute optogenetic activation of serotonergic neurons enhanced feedback circuit activity, whereas cholinergic activation suppressed it, revealing a balanced interplay between these opposing neuromodulatory pathways. Moreover, repeated pairing of serotonin or acetylcholine activation with visual stimulation induced distinct forms of stimulus specific plasticity selectively restricted to feedback pathways. Together, these findings demonstrate that serotonergic and cholinergic modulation exert opposing influences on cortical feedback circuit., uncovering a neuromodulator-specific mechanism that gates sensory processing and plasticity of sensory representations in the visual cortex.