When deciding while acting, such as sequentially selecting targets during naturalistic foraging, movement trajectories reveal the dynamics of the unfolding decision process. Ongoing and planned actions may impact decisions in these situations in addition to expected reward outcomes. Here, we test how strongly humans weigh and how fast they integrate individual constituents of expected value, namely the prior probability (PROB) of an action and the prior expected reward amount (AMNT) associated with an action, when deciding based on the combination of both together during an ongoing movement. Unlike other decision-making studies, we focus on PROB and AMNT priors, and not final evidence, in that correct actions were either instructed or could be chosen freely. This means, there was no decision-making under risk. We show that both priors gradually influence movement trajectories already before mid-movement instructions of the correct target and bias free-choice behavior. These effects were consistently strong...

Brain stores new information by modifying connections between neurons. When new information is learnt, a group of neurons gets activated and they are connected to each other via synapses. Dendritic spines are protrusions along neuronal dendrites where excitatory synapses are located. Dendritic spines are the first structures to protrude out from the dendrite to reach out to other neurons and establish a new connection. Thus, it is expected that neuronal activity enhances spine initiation. However, the molecular mechanisms linking neuronal activity to spine initiation are poorly known. Membrane binding BAR domain proteins are involved in spine initiation, but it is not known whether neuronal activity affects BAR domain proteins. Here, we used bicuculline treatment to activate excitatory neurons in organotypic hippocampal slices. With this experimental setup, we identified F-BAR domain containing growth arrest-specific protein (Gas7) as a novel spine initiation factor responding to neuron activity. Upon bicu...

Taste cells are maintained by continuous turnover throughout a lifetime, yet the mechanisms of taste cell differentiation, and how taste sensations remain constant despite this continuous turnover, remain poorly understood. Here, we report that a transcription factor Etv1 (also known as Er81) is involved in the differentiation of taste cells responsible for the preference for sweet, umami, and salty tastes. Molecular analyses revealed that Etv1 is expressed by a subset of taste cells that depend on Skn-1a (also known as Pou2f3) for their generation and express T1R genes (responsible for sweet and umami tastes) or Scnn1a (responsible for amiloride-sensitive salty taste). Etv1CreERT2/CreERT2 mice express Etv1 isoform(s) but not Etv1 in putative proprioceptive neurons as comparable to wild-type mice, yet lack expression of Etv1 or an isoform in taste cells. These Etv1CreERT2/CreERT2 mice have the same population of Skn-1a-dependent cells in taste buds as wild-type mice but have altered gene expression in tast...

Midbrain dopamine (DA) neurons are among the best characterized pacemaker neurons, having intrinsic, rhythmic firing activity even in the absence of synaptic input. However, the mechanisms of DA neuron pacemaking have not been systematically related to how these cells respond to synaptic input. The input–output properties of pacemaking neurons can be characterized by the phase-resetting curve (PRC), which describes the sensitivity of interspike interval (ISI) length to inputs arriving at different phases of the firing cycle. Here we determined PRCs of putative DA neurons in the substantia nigra pars compacta in brain slices from male and female mice using gramicidin-perforated current-clamp recordings with electrical noise stimuli applied through the patch pipette. On average, and compared with nearby putative GABA neurons, DA neurons showed a low, nearly constant level of sensitivity across most of the ISI, but individual cells had PRCs showing relatively greater sensitivity at early or late phases. Pharm...

Vagal sensory neurons (VSNs) located in the nodose ganglion provide information, such as stomach stretch or the presence of ingested nutrients, to the caudal medulla via specialized cell types expressing unique marker genes. Here, we leverage VSN marker genes identified in adult mice to determine when specialized vagal subtypes arise developmentally and the trophic factors that shape their growth. Experiments to screen for trophic factor sensitivity revealed that brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) robustly stimulate neurite outgrowth from VSNs in vitro . Perinatally, BDNF was expressed by neurons of the nodose ganglion itself, while GDNF was expressed by intestinal smooth muscle cells. Thus, BDNF may support VSNs locally, whereas GDNF may act as a target-derived trophic factor supporting the growth of processes at distal innervation sites in the gut. Consistent with this, expression of the GDNF receptor was enriched in VSN cell types that project to t...

The nasal epithelium houses a population of solitary chemosensory cells (SCCs). SCCs express bitter taste receptors and taste transduction signaling components and are innervated by peptidergic trigeminal polymodal nociceptive nerve fibers. Thus, nasal SCCs respond to bitter compounds, including bacterial metabolites, and these reactions evoke protective respiratory reflexes and innate immune and inflammatory responses. We tested whether SCCs are implicated in aversive behavior to specific inhaled nebulized irritants using a custom-built dual-chamber forced-choice device. The behavior of mice was recorded and analyzed for the time spent in each chamber. Wild-type (WT) mice exhibited an aversion to 10 mm denatonium benzoate (Den) or cycloheximide and spent more time in the control (saline) chamber. The SCC-pathway knock-out (KO) mice did not exhibit such an aversion response. The bitter avoidance behavior of WT mice was positively correlated with the concentration increase of Den and the number of exposures...

Humans exhibit lateralization such that most individuals typically show a preference for using one arm over the other for a range of movement tasks. The computational aspects of movement control leading to these differences in skill are not yet understood. It has been hypothesized that the dominant and nondominant arms differ in terms of the use of predictive or impedance control mechanisms. However, previous studies present confounding factors that prevented clear conclusions: either the performances were compared across two different groups, or in a design in which asymmetrical transfer between limbs could take place. To address these concerns, we studied a reach adaptation task during which healthy volunteers performed movements with their right and left arms in random order. We performed two experiments. Experiment 1 (18 participants) focused on adaptation to the presence of a perturbing force field (FF) and experiment 2 (12 participants) focused on rapid adaptations in feedback responses. The randomiz...

The occurrence of tics in Tourette syndrome (TS) has often been linked to impaired cognitive control, but empirical findings are still inconclusive. A recent view proposes that tics may be the result of an abnormally strong interrelation between perceptual processes and motor actions, commonly referred to as perception-action binding. The general aim of the present study was to examine proactive control and binding effects in the context of task switching in adult human patients with TS and matched healthy controls. A cued task switching paradigm was employed in 24 patients (18 male, 6 female) and 25 controls while recording electroencephalography (EEG). Residue iteration decomposition (RIDE) was applied to analyze cue-locked proactive cognitive control and target-locked binding processes. Behavioral task switching performance was unaltered in patients with TS. A cue-locked parietal switch positivity, reflecting proactive control processes involved in the reconfiguration of the new task did not differ betw...

A key assumption in studies of cortical functions is that excitatory principal neurons, but not inhibitory cells express calcium/calmodulin-dependent protein kinase II subunit α (CaMKIIα) resulting in a widespread use of CaMKIIα promoter-driven protein expression for principal cell manipulation and monitoring their activities. Using neuroanatomical and electrophysiological methods we demonstrate that in addition to pyramidal neurons, multiple types of cortical GABAegic cells are targeted by adeno-associated viral vectors (AAV) driven by the CaMKIIα promoter in both male and female mice. We tested the AAV5 and AAV9 serotype of viruses with either Channelrhodopsin 2 (ChR2)-mCherry or Archaerhodopsin-T-green fluorescent protein (GFP) constructs, with different dilutions. We show that in all cases, the reporter proteins can visualize a large fraction of different interneuron types, including parvalbumin (PV), somatostatin (SST), neuronal nitric oxide synthase (nNOS), neuropeptide Y (NPY), and cholecystokinin (...

Investigation of rodent drinking behavior has provided insight into drivers of thirst, circadian rhythms, anhedonia, and drug and ethanol consumption. Traditional methods of recording fluid intake involve weighing bottles, which is cumbersome and lacks temporal resolution. Several open-source devices have been designed to improve drink monitoring, particularly for two-bottle choice tasks. However, beam-break sensors lack the ability to detect individual licks for bout microstructure analysis. Thus, we designed LIQ HD (Lick Instance Quantifier Home cage Device) with the goal of utilizing capacitive sensors to increase accuracy and analyze lick microstructure, building a device compatible with ventilated home cages, increasing scale with prolonged undisturbed recordings, and creating a design that is easy to build and use with an intuitive touchscreen graphical user interface. The system tracks two-bottle choice licking behavior in up to 18 rodent cages, or 36 single bottles, on a minute-to-minute timescale ...