Abstract
Originating from the brainstem raphe nuclei, serotonin is an important neuromodulator involved in a variety of physiological and pathological functions. Specific optogenetic stimulation of serotonergic neurons results in the divisive suppression of spontaneous, but not sensory evoked activity in the majority of neurons in the primary olfactory cortex and an increase in firing in a minority of neurons. To reveal the mechanisms involved in this dual serotonergic control of cortical activity we used a combination of in vitro electrophysiological recordings from identified neurons in the primary olfactory cortex, optogenetics and pharmacology and found that serotonin suppressed the activity of principal neurons, but excited local interneurons. The results have important implications in sensory information processing and other functions of the olfactory cortex and related brain areas.
Highlights
Serotonin (5-hydroxytryptamine, 5-HT1a receptor antagonist WAY 100635 (5-HT)) originates from neurons located in the brainstem raphe nuclei projecting to various forebrain structures including the primary olfactory cortex, the anterior piriform cortex and is involved in various physiological and pathological phenomena including sensory and motor responses as well as the regulation of mood and impulsivity (Okaty et al, 2019)
Both the hyperpolarization (5-HT: – 2.64 ± 0.47 mV, WAY100635 + 5-HT: 0.05 ± 0.14 mV, p < 0.05, Wilcoxon signed-rank test, n = 5) and the suppression of action potential firing could be prevented by the bath application of the 5-HT1a receptor antagonist WAY 100635 (5-HT: 1.58 ± 1.01%, WAY100635 + 5-HT: 108.93 ± 1.57%, p < 0.001,Wilcoxon signed-rank test n = 5) suggesting the effect of 5-HT on pyramidal neurons is mediated by 5-HT1 receptors (Figures 1B–D)
When 5-HT was focally applied near the somata of various identified interneurons while monitoring their membrane potential, the cells were depolarized (5-HT: 7.30 ± 3.24 mV, n = 5) and this depolarization led to action potential firing in all the recorded interneurons (Figure 1E)
Summary
Serotonin (5-hydroxytryptamine, 5-HT) originates from neurons located in the brainstem raphe nuclei projecting to various forebrain structures including the primary olfactory cortex, the anterior piriform cortex (aPC) and is involved in various physiological and pathological phenomena including sensory and motor responses as well as the regulation of mood and impulsivity (Okaty et al, 2019). Specific stimulation of 5-HT neurons has a multiplicative and frequencydependent effect on the baseline activity of aPC neurons, but no effect on odor evoked responses (Lottem et al, 2016). In the hippocampus, the effects of 5HT are both cell-type specific affecting cholecystokinin-expressing and O-LM interneurons, but not parvalbumin-expressing basket cells, and input specific, affecting only glutamatergic synaptic transmission originating from CA1 pyramidal cells (Winterer et al, 2011; Bohm et al, 2015).
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