Hunger and thirst drive animals’ consumption behavior and regulate their decision-making concerning rewards. We previously assessed the thirst states of monkeys by measuring blood osmolality under controlled water access and examined how these thirst states influenced their risk-taking behavior in decisions involving fluid rewards. However, hunger assessment in monkeys remains poorly performed. Moreover, the lack of precise measures for hunger states leads to another issue regarding how hunger and thirst states interact with each other in each individual. Thus, when controlling food access to motivate performance, it remains unclear how these two physiological needs are satisfied in captive monkeys. Here, we measured blood ghrelin and osmolality levels to respectively assess hunger and thirst in four captive macaques. Using an enzyme-linked immunosorbent assay, we identified that the levels of blood ghrelin, a widely measured hunger-related peptide hormone in humans, were high after 20 h of no food access ...

The electrophysiological response to rewards recorded during laboratory tasks has been well documented, yet little is known about the neural response patterns in a more naturalistic setting. Here, we combined a mobile-EEG system with an augmented reality headset to record event-related brain potentials (ERPs) while participants engaged in a naturalistic operant task to find rewards. Twenty-five participants were asked to navigate toward a west or east goal location marked by floating orbs, and once participants reached the goal location, the orb would then signify a reward (5 cents) or no-reward (0 cents) outcome. Following the outcome, participants returned to a start location marked by floating purple rings, and once standing in the middle, a 3 s counter signaled the next trial, for a total of 200 trials. Consistent with previous research, reward feedback evoked the reward positivity, an ERP component believed to index the sensitivity of the anterior cingulate cortex to reward prediction error signals. T...

Single-unit (SU) activity—action potentials isolated from one neuron—has traditionally been employed to relate neuronal activity to behavior. However, recent investigations have shown that multiunit (MU) activity—ensemble neural activity recorded within the vicinity of one microelectrode—may also contain accurate estimations of task-related neural population dynamics. Here, using an established model-fitting approach, we compared the spatial codes of SU response fields with corresponding MU response fields recorded from the frontal eye fields (FEFs) in head-unrestrained monkeys ( Macaca mulatta ) during a memory-guided saccade task. Overall, both SU and MU populations showed a simple visuomotor transformation: the visual response coded target-in-eye coordinates, transitioning progressively during the delay toward a future gaze-in-eye code in the saccade motor response. However, the SU population showed additional secondary codes, including a predictive gaze code in the visual response and retention of a ta...

While injury responses are generally well studied, the focus tends to be on axon regeneration, leaving dendrite-specific contribution after injury and the regeneration process less understood. After axons are injured, the area distal to the crush site degenerates, and injury signaling is initiated by a retrograde calcium wave that activates stress signaling including dual leucine zipper kinase (DLK)/JNK activation, transcription of regeneration associated genes, and directed local translation which allows ultimately for reinitiation of axon outgrowth. Potential for outgrowth is greater in the peripheral nervous system as compared with that in the central. Dendrites, like axons, are vulnerable to injury from stroke, seizure, and traumatic injury, but limitations in the ability to generate a targeted injury and the inability to track dendrites of individual cells in vertebrate models make the study of dendrite injury and regeneration difficult. Advancements have been made in the use of lasers to induce preci...

Moving effectively is essential for any animal. Thus, many different kinds of brain processes likely contribute to learning and adapting movement. How these contributions are combined is unknown. Nevertheless, the field of motor adaptation has been working under the assumption that measures of explicit and implicit motor adaptation can simply be added in total adaptation. While this has been tested, we show that these tests were insufficient. We put this additivity assumption to the test in various ways and find that measures of implicit and explicit adaptation are not additive. This means that future studies should measure both implicit and explicit adaptation directly. It also challenges us to disentangle how various motor adaptation processes do combine when producing movements and may have implications for our understanding of other kinds of learning as well (data and code: <https://osf.io/3yhw5>).

Cognitive dysfunction is associated with methamphetamine use disorder (MUD). Here, we used genetic and pharmacological approaches to examine the involvement of either Group 2 metabotropic glutamate (mGlu2) or mGlu3 receptors in memory deficit induced by methamphetamine in mice. Methamphetamine treatment (1 mg/kg, i.p., once a day for 5 d followed by 7 d of withdrawal) caused an impaired performance in the novel object recognition test in wild-type mice, but not in mGlu2−/− or mGlu3−/− mice. Memory deficit in wild-type mice challenged with methamphetamine was corrected by systemic treatment with selectively negative allosteric modulators of mGlu2 or mGlu3 receptors (compounds VU6001966 and VU0650786, respectively). Methamphetamine treatment in wild-type mice caused large increases in levels of mGlu2/3 receptors, the Type 3 activator of G-protein signaling (AGS3), Rab3A, and the vesicular glutamate transporter, vGlut1, in the prefrontal cortex (PFC). Methamphetamine did not alter mGlu2/3-mediated inhibition ...

Adaptive behavior relies on efficient cognitive control. The anterior cingulate cortex (ACC) is a key node within the executive prefrontal network. The reciprocal connectivity between the locus ceruleus (LC) and ACC is thought to support behavioral reorganization triggered by the detection of an unexpected change. We transduced LC neurons with either excitatory or inhibitory chemogenetic receptors in adult male rats and trained rats on a spatial task. Subsequently, we altered LC activity and confronted rats with an unexpected change of reward locations. In a new spatial context, rats with decreased noradrenaline (NA) in the ACC entered unbaited maze arms more persistently which was indicative of perseveration. In contrast, the suppression of the global NA transmission reduced perseveration. Neither chemogenetic manipulation nor inactivation of the ACC by muscimol affected the rate of learning, possibly due to partial virus transduction of the LC neurons and/or the compensatory engagement of other prefronta...

Adults heard recordings of two spatially separated speakers reading newspaper and magazine articles. They were asked to listen to one of them and ignore the other, and EEG was recorded to assess their neural processing. Machine learning extracted neural sources that tracked the target and distractor speakers at three levels: the acoustic envelope of speech (delta- and theta-band modulations), lexical frequency for individual words, and the contextual predictability of individual words estimated by GPT-4 and earlier lexical models. To provide a broader view of speech perception, half of the subjects completed a simultaneous visual task, and the listeners included both native and non-native English speakers. Distinct neural components were extracted for these levels of auditory and lexical processing, demonstrating that native English speakers had greater target–distractor separation compared with non-native English speakers on most measures, and that lexical processing was reduced by the visual task. Moreov...

In 1987, while investigating the iap gene in Escherichia coli , Nakata and colleagues identified “five highly homologous sequences of 29 nucleotides were arranged as direct repeats with 32 nucleotides as spacing.” Perplexed by this discovery, the authors stated, “so far, no sequence homologous to these has been found elsewhere in prokaryotes, and the biological significance of these sequences is not known.” These few sentences launched a decades-long investigation into the biological mystery of clustered regularly interspaced short palindromic repeats, or CRISPR (Ishino et al., 1987). Since its first identification, CRISPR—an adaptive immune response in prokaryotic organisms to recognize and combat infectious DNA—has been developed into a tool for targeted gene editing in a variety of cells and organisms (Jansen et al., 2002). The utility of CRISPR lies in the easy targeting of virtually any genomic location by a short RNA guide. In its simplest form, the two components that must be expressed in cells to ...

The medial prefrontal cortex (mPFC) plays a pivotal role in regulating working memory, executive function, and self-regulatory behaviors. Dysfunction in the mPFC circuits is a characteristic feature of several neuropsychiatric disorders including schizophrenia, depression, and post-traumatic stress disorder. Chronic stress (CS) is widely recognized as a major triggering factor for the onset of these disorders. Although evidence suggests synaptic dysfunction in mPFC circuits following CS exposure, it remains unclear how different neuronal populations in the infralimbic (IL) and prelimbic (PL) cortices are affected in terms of synaptic inhibition/excitation balance ( I / E ratio). Here, using neuroproteomic analysis and whole-cell patch-clamp recordings in pyramidal neurons (PNs) and parvalbumin (PV) interneurons within the PL and IL cortices, we examined the synaptic changes after 21 d of chronic unpredictable stress, in male mice. Our results reveal distinct impacts of CS on PL and IL PNs, resulting in an ...