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 ...

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...

It has long been assumed that activity patterns persist in neuronal circuits after they are first experienced, as part of the process of information processing and storage by the brain. However, these “reverberations” of current activity have not been directly observed on a single-neuron level in a mammalian system. Here we demonstrate that specific induced activity patterns are retained in mature cultured hippocampal neuronal networks. Neurons within the network are induced to fire at a single frequency or in a more complex pattern containing two distinct frequencies. After the stimulation was stopped, the subsequent neuronal activity of hundreds of neurons in the network was monitored. In the case of single-frequency stimulation, it was observed that many of the neurons continue to fire at the same frequency that they were stimulated to fire at. Using a recurrent neural network trained to detect specific, more complex patterns, we found that the multiple-frequency stimulation patterns were also retained ...

Recent neurophysiological studies provide inconsistent results of frontoparietal network (FPN) stimulation for altering working memory (WM) capacity. This study aimed to boost WM capacity by manipulating the activity of the FPN via dual-site high–definition transcranial direct current stimulation. Forty-eight participants were randomly assigned to three stimulation groups, receiving either simultaneous anodal stimulation of the frontal and parietal areas (double stimulation), or stimulation of the frontal area only (single stimulation), or the placebo stimulation (sham) to frontal and parietal areas. After the stimulation, we used an operation span task to test memory accuracy, mathematical accuracy, time of calculation and memorizing, and recall response time across the three groups. The results revealed an enhancement of memory accuracy and a reduction of time of calculation in the double stimulation group compared with that in others. In addition, recall response time was significantly decreased in the ...

Adolescent inhibition of thalamocortical projections from postnatal days P20 to 50 leads to long-lasting deficits in prefrontal cortex function and cognition in the adult mouse. While this suggests a role of thalamic activity in prefrontal cortex maturation, it is unclear how inhibition of these projections affects prefrontal circuitry during adolescence. Here, we used chemogenetic tools to inhibit thalamoprefrontal projections in male/female mice from P20 to P35 and measured synaptic inputs to prefrontal pyramidal neurons by layer (either II/III or V/VI) and projection target (mediodorsal thalamus (MD), nucleus accumbens (NAc), or callosal prefrontal projections) 24 h later using slice physiology. We found a decrease in the frequency of excitatory and inhibitory currents in layer II/III NAc and layer V/VI MD-projecting neurons while layer V/VI NAc-projecting neurons showed an increase in the amplitude of excitatory and inhibitory currents. Regarding cortical projections, the frequency of inhibitory but no...

The frontal cortex-striatum circuit plays a pivotal role in adaptive goal-directed behaviors. However, it remains unclear how decision-related signals are mediated through cross-regional transmission between the medial frontal cortex and the striatum by neuronal ensembles in making decision based on outcomes of past action. Here, we analyzed neuronal ensemble activity obtained through simultaneous multiunit recordings in the secondary motor cortex (M2) and dorsal striatum (DS) in rats performing an outcome-based left-or-right choice task. By adopting tensor component analysis (TCA), a single-trial–based unsupervised dimensionality reduction approach, for concatenated ensembles of M2 and DS neurons, we identified distinct three spatiotemporal neural dynamics (TCA components) at the single-trial level specific to task-relevant variables. Choice-position–selective neural dynamics reflected the positions chosen and was correlated with the trial-to-trial fluctuation of behavioral variables. Intriguingly, choice...

Episodic memory, the ability to recall specific events and experiences, is a cornerstone of human cognition with profound clinical implications. While animal studies have provided valuable insights into the neuronal underpinnings of episodic memory, research has largely relied on a limited subset of tasks that model only some aspects of episodic memory. In this narrative review, we provide an overview of rodent episodic-like memory tasks that expand the methodological repertoire and diversify the approaches used in episodic-like memory research. These tasks assess various aspects of human episodic memory, such as integrated what–where–when or what–where memory , source memory, free recall, temporal binding, and threshold retrieval dynamics. We review each task’s general principle and consider whether alternative non-episodic mechanisms can account for the observed behavior. While our list of tasks is not exhaustive, we hope it will guide researchers in selecting models that align with their specific resear...

Volatile anesthetics are currently believed to cause unconsciousness by acting on one or more molecular targets including neural ion channels, receptors, mitochondria, synaptic proteins, and cytoskeletal proteins. Anesthetic gases including isoflurane bind to cytoskeletal microtubules (MTs) and dampen their quantum optical effects, potentially contributing to causing unconsciousness. This possibility is supported by the finding that taxane chemotherapy consisting of MT-stabilizing drugs reduces the effectiveness of anesthesia during surgery in human cancer patients. In order to experimentally assess the contribution of MTs as functionally relevant targets of volatile anesthetics, we measured latencies to loss of righting reflex (LORR) under 4% isoflurane in male rats injected subcutaneously with vehicle or 0.75 mg/kg of the brain-penetrant MT–stabilizing drug epothilone B (epoB). EpoB-treated rats took an average of 69 s longer to become unconscious as measured by latency to LORR. This was a statistically ...

Uncovering the relationships between neural circuits, behavior, and neural dysfunction may require rodent pose tracking. While open-source toolkits such as DeepLabCut have revolutionized markerless pose estimation using deep neural networks, the training process still requires human intervention for annotating key points of interest in video data. To further reduce human labor for neural network training, we developed a method that automatically generates annotated image datasets of rodent paw placement in a laboratory setting. It uses invisible but fluorescent markers that become temporarily visible under UV light. Through stroboscopic alternating illumination, adjacent video frames taken at 720 Hz are either UV or white light illuminated. After color filtering the UV-exposed video frames, the UV markings are identified and the paw locations are deterministically mapped. This paw information is then transferred to automatically annotate paw positions in the next white light-exposed frame that is later use...