Prolonged activation of carbon dioxide-sensitive neurons in mosquitoes

Many insects can detect carbon dioxide (CO 2 ) plumes using a conserved receptor made up of members of the gustatory receptor (Gr) family Gr1, Gr2 and Gr3. Mosquitoes are attracted to host animals for blood meals using plumes of CO 2 in the exhaled breath using the receptor expressed in the A neuron of the capitate peg sensilla type on the maxillary palps. The receptor is known to also detect several other classes of odorants, including ones emitted from human skin. Here, we discover that a common skin odorant, butyric acid, can cause a phasic activation followed by an unusually prolonged tonic activity after the stimulus is over in the CO 2 neurons of mosquitoes. The effect is conserved in both Aedes aegypti and Anopheles gambiae mosquitoes. This raises a question about its role in a mosquito's preference for the skin odour of different individuals. Butyric acid belongs to a small number of odorants known to cause the prolonged activation of the CO 2 receptor. A chemical informatic analysis identifies a specific set of physico-chemical features that can be used in a machine learning predictive model for the prolonged activators. Interestingly, this set is different from physico-chemical features selected for activators or inhibitors, indicating that each has a distinct structural basis. The structural understanding opens up an opportunity to find novel ligands to manipulate the CO 2 receptor and mosquito behaviour.

Inter-and intra-individual coupling between pupillary, electrophysiological, and behavioral responses in a visual oddball task

Although the P3b component of the event-related brain potential is one of the most widely-studied components, its underlying generators are not currently well understood. Recent theories have suggested that the P3b is triggered by phasic activation of the locus-coeruleus norepinephrine (LC-NE) system, an important control center implicated in facilitating optimal task-relevant behavior. Previous research has reported strong correlations between pupil dilation and LC activity, suggesting that pupil diameter is a useful indicator for ongoing LC-NE activity. Given the strong relationship between LC activity and pupil dilation, if the P3b is driven by phasic LC activity, there should be a robust trial-to-trial relationship with the phasic pupillary dilation response (PDR). However, previous work examining relationships between concurrently recorded pupillary and P3b responses has not supported this. One possibility is that the relationship between the measures might be carried primarily by either inter-individual (i.e., between-participant) or intra-individual (i.e., within-participant) contributions to coupling, and prior work has not systematically delineated these relationships. Doing so in the current study, we do not find evidence for either inter-individual or intra-individual relationships between the PDR and P3b responses. However, baseline pupil dilation did predict the P3b. Interestingly, both the PDR and P3b independently predicted inter-individual and intra-individual variability in decision response time. Implications for the LC-P3b hypothesis are discussed.

Phasic activation of dorsal raphe serotonergic neurons increases pupil-linked arousal

SUMMARYVariations in pupil size under constant luminance are closely coupled to changes in arousal state [1–5]. It is assumed that such fluctuations are primarily controlled by the noradrenergic system [6–9]. Phasic activity of noradrenergic axons precedes pupil dilations associated with rapid changes in arousal [7,9], and is believed to be driven by unexpected uncertainty [1,10–16]. However, the role of other modulatory pathways in the control of pupil-linked arousal has not been as thoroughly investigated, but evidence suggests that noradrenaline may not be alone [7,17,18]. Administration of serotonergic drugs seems to affect pupil size [19–23], but these effects have not been investigated in detail. Here, we show that transient serotonin (5-HT) activation, like noradrenaline, causes pupil-size changes. We used phasic optogenetic activation of 5-HT neurons in the dorsal raphe nucleus (DRN) in head-fixed mice locomoting in a foraging task. 5-HT-driven modulations of pupil size were maintained throughout the photostimulation period and sustained for several seconds after the end of the stimulation. The activation of 5-HT neurons increased pupil size additively with locomotor speed, suggesting that 5-HT transients affect pupil-linked arousal independently from locomotor states. We found that the effect of 5-HT on pupil size depended on the level of environmental uncertainty, consistent with the idea that 5-HT may report a salience or surprise signal [24]. Together, these results challenge the classic view of the neuromodulatory control of pupil-linked arousal, revealing a tight relationship between the activation of 5-HT neurons and changes in pupil size.

Coincidence of cholinergic pauses, dopaminergic activation and depolarization drives synaptic plasticity in the striatum

Pauses in the firing of tonically-active cholinergic interneurons (ChIs) in the striatum coincide with phasic activation of dopamine neurons during reinforcement learning. However, how this pause influences cellular substrates of learning is unclear. Using two in vivo paradigms, we report that long-term potentiation (LTP) at corticostriatal synapses with spiny projection neurons (SPNs) is dependent on the temporal coincidence of ChI pause and dopamine phasic activation, critically accompanied by SPN depolarization.

Sudden Events Change Old Visual Objects Into New Ones: A Possible Role for Phasic Activation of Locus Coeruleus

We report a novel visual phenomenon called the rejuvenation effect. It causes an “old” object that has been on view for some time to acquire the properties of a suddenly appearing new object. In each experiment, a square outline was displayed continuously on one side of fixation. The target (an asterisk) was presented either inside the square or on the opposite side of fixation. On half of the trials, a transient visual or auditory event preceded the target. In Experiment 1a ( N = 139), response times were faster when the target appeared inside the square, but only when it was preceded by a transient event, consistent with the network-reset theory of locus coeruleus-norepinephrine (LC-NE) phasic activation. Three further experiments confirmed the predictions of network-reset theory, including the absence of rejuvenation in participants with atypical LC-NE functioning (individuals with symptoms of autism spectrum disorder). These findings provide new perspectives on what causes a visual object to be perceived as new.

Brainwide mapping of endogenous serotonergic transmission via chemogenetic-fMRI

ABSTRACTSerotonergic transmission affects behaviours and neuro-physiological functions via the orchestrated recruitment of distributed neural systems. It is however unclear whether serotonin’s modulatory effect entails a global regulation of brainwide neural activity, or is relayed and encoded by a set of primary functional substrates. Here we combine DREADD-based chemogenetics and mouse fMRI, an approach we term “chemo-fMRI”, to causally probe the brainwide substrates modulated by phasic serotonergic activity. We describe the generation of a conditional knock-in mouse line that, crossed with serotonin-specific Cre-recombinase mice, allowed us to remotely stimulate serotonergic neurons during fMRI scans. We show that chemogenetic stimulation of the serotonin system does not affect global brain activity, but results in region-specific activation of a set of primary target regions encompassing parieto-cortical, hippocampal, and midbrain structures, as well as ventro-striatal components of the mesolimbic reward systems. Many of the activated regions also exhibit increased c-Fos immunostaining upon chemogenetic stimulation in freely-behaving mice, corroborating a neural origin for the observed functional signals. These results identify a set of regional substrates that act as primary functional targets of endogenous serotonergic stimulation, and establish causation between phasic activation of serotonergic neurons and regional fMRI signals. They further highlight a functional cross-talk between serotonin and mesolimbic dopamine systems hence providing a novel framework for understanding serotonin dependent functions and interpreting data obtained from human fMRI studies of serotonin modulating agents.