The nucleus accumbens (NAc) is a critical component of a limbic basal ganglia circuit that is thought to play an important role in decision-making and the processing of rewarding stimuli. As part of this circuit, dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) of the NAc core are known to send a major projection to the substantia nigra pars reticulata (SNr). However, the functional role of this SNr-projecting NAc D1-MSN (NAcD1-MSN–SNr) pathway is still largely uncharacterized. Moreover, as the SNr is thought to belong to both limbic and motor information-processing basal ganglia loops, it is possible that the NAcD1-MSN–SNr pathway may be able to influence both limbic and motor functions. In this study, we investigated the effect of optogenetic manipulation of the NAcD1-MSN–SNr pathway on reward-learning and locomotor behavior in male mice. Stimulation of the axon terminals of NAc core D1-MSNs in the SNr induced a preference for a laser-paired location, self-stimulation via a laser-paired lev...

Post-traumatic stress disorder and other mental disorders can be treated by an established psychotherapy called Eye Movement Desensitization and Reprocessing (EMDR). In EMDR, patients are confronted with traumatic memories while they are stimulated with alternating bilateral stimuli (ABS). How ABS affects the brain and whether ABS could be adapted to different patients or mental disorders is unknown. Interestingly, ABS reduced conditioned fear in mice. Yet, an approach to systematically test complex visual stimuli and compare respective differences in emotional processing based on semiautomated/automated behavioral analysis is lacking. We developed 2MDR (MultiModal Visual Stimulation to Desensitize Rodents), a novel, open-source, low-cost, customizable device that can be integrated in and transistor–transistor logic (TTL) controlled by commercial rodent behavioral setups. 2MDR allows the design and precise steering of multimodal visual stimuli in the head direction of freely moving mice. Optimized videogra...

Despite the significant health consequences of anxiety, the neural basis of regulation for personal anxious events is not well understood. We examined brain activity and functional connectivity during cognitive emotion regulation strategies (reappraisal and acceptance) for personal anxious events. Functional MRI (fMRI) data were obtained while 35 college students were thinking about (the control condition), reappraising, or accepting their own anxiety-provoking situations. Although reappraisal and acceptance decreased anxiety, no statistically significant differences were observed in the brain activation levels between cognitive emotion regulation strategies and the control condition. However, acceptance decreased activation in the posterior cingulate cortex and precuneus more than reappraisal. Moreover, functional connectivity with the amygdala and ventral anterior insula distinguished the emotion regulation strategies for anxiety. Reappraisal showed stronger negative functional connectivity with the amyg...

Vestibulospinal neurons integrate sensed imbalance to regulate postural reflexes. As an evolutionarily conserved neural population, understanding their synaptic and circuit-level properties can offer insight into vertebrate antigravity reflexes. Motivated by recent work, we set out to verify and extend the characterization of vestibulospinal neurons in the larval zebrafish. Using current-clamp recordings together with stimulation, we observed that larval zebrafish vestibulospinal neurons are silent at rest, yet capable of sustained spiking following depolarization. Neurons responded systematically to a vestibular stimulus (translation in the dark); responses were abolished after chronic or acute loss of the utricular otolith. Voltage-clamp recordings at rest revealed strong excitatory inputs with a characteristic multimodal distribution of amplitudes, as well as strong inhibitory inputs. Excitatory inputs within a particular mode (amplitude range) routinely violated refractory period criteria and exhibited...

Ketamine, an NMDA antagonist, is widely used in clinical settings. Recently, low-dose ketamine has gained attention because of its promising role as a rapid antidepressant. However, the effects of low-dose ketamine on brain function, particularly higher cognitive functions of primate brains, are not fully understood. In this study, we used two macaques as subjects and found that acute low-dose ketamine administration significantly impaired the ability for arbitrary visuomotor mapping (AVM), a form of associative learning (AL) essential for flexible behaviors, including executions of learned stimuli-response contingency or learning of new contingencies. We conducted in-depth analyses and identified intrinsic characteristics of these ketamine-induced functional deficits, including lowered accuracy, prolonged time for planning and movement execution, increased tendency to make errors when visual cues are changed from trial to trial, and stronger impact on combining associative learning and another key higher ...

It is well known that both hand movements and mental representations of movement lead to event-related desynchronization (ERD) of the electroencephalogram (EEG) recorded over the corresponding cortical motor areas. However, the relationship between ERD in somatosensory cortical areas and mental representations of tactile sensations is not well understood. In this study, we employed EEG recordings in healthy humans to compare the effects of real and imagined vibrotactile stimulation of the right hand. Both real and imagined sensations produced contralateral ERD patterns, particularly in the μ-band and most significantly in the C3 region. Building on these results and the previous literature, we discuss the role of tactile imagery as part of the complex body image and the potential for using EEG patterns induced by tactile imagery as control signals in brain-computer interfaces (BCIs). Combining this approach with motor imagery (MI) could improve the performance of BCIs intended for rehabilitation of sensori...

Despite their involvement in many cognitive functions, β oscillations are among the least understood brain rhythms. Reports on whether the functional role of β is primarily inhibitory or excitatory have been contradictory. Our framework attempts to reconcile these findings and proposes that several β rhythms co-exist at different frequencies. β Frequency shifts and their potential influence on behavior have thus far received little attention. In this human magnetoencephalography (MEG) experiment, we asked whether changes in β power or frequency in auditory cortex and motor cortex influence behavior (reaction times) during an auditory sweep discrimination task. We found that in motor cortex, increased β power slowed down responses, while in auditory cortex, increased β frequency slowed down responses. We further characterized β as transient burst events with distinct spectro-temporal profiles influencing reaction times. Finally, we found that increased motor-to-auditory β connectivity also slowed down respo...

Synaptic modification in postnatal development is essential for the maturation of neural networks. Developmental maturation of excitatory synapses occurs at the loci of dendritic spines that are dynamically regulated by growth and pruning. Striatal spiny projection neurons (SPNs) receive excitatory input from the cerebral cortex and thalamus. SPNs of the striatonigral direct pathway (dSPNs) and SPNs of the striatopallidal indirect pathway (iSPNs) have different developmental roots and functions. The spatial and temporal dynamics of dendritic spine maturation of these two types of SPNs remain elusive. Here, we delineate the developmental trajectories of dendritic spines of dSPNs and iSPNs in the caudoputamen and nucleus accumbens (NAc). We labeled dendritic spines of SPNs by microinjecting Cre-dependent AAV-eYFP viruses into newborn Drd1-Cre or Adora2a-Cre mice, and analyzed spinogenesis at three levels, including different SPN cell types, subregions and postnatal times. In the dorsolateral striatum, spine ...

The midbrain periaqueductal gray (PAG), particularly its ventrolateral column (vlPAG), is part of a key descending pathway that modulates nociception, fear and anxiety behaviours in both humans and rodents. It has been previously demonstrated that inhibitory GABAergic neurons within the vlPAG have a major role in this nociceptive modulation. However, the PAG contains a diverse range of neuronal subtypes and the contribution of different subtypes of inhibitory neurons to nociceptive control has not been investigated. Here, we employed a chemogenetic strategy in mice that express Cre- under the promotor for the glycine transporter 2 (GlyT2::cre) to modulate a novel group of glycinergic neurons within the vlPAG and then investigate their role in nociceptive control. We show that activation of GlyT2-PAG neurons enhances cold and noxious heat responses and increases locomotor activity in both male and female mice. In contrast, inhibition of GlyT2-PAG neurons reduced nociceptive responses, while locomotor behavi...

Nicotine is an addictive drug whose popularity has recently increased, particularly among adolescents, due to the availability of electronic nicotine devices ( i.e., “vaping”) and nicotine e-liquids containing additives with rich chemosensory properties. Some efforts to understand the role of these additives in nicotine reward suggest that they increase nicotine reward and reinforcement, but the sensory contributions of additives, especially in their vapor forms, are largely untested. Here, to better understand how a fruit-flavored ( i.e., strawberry) additive influences nicotine reward and aversion, we used a conditioned place preference (CPP) procedure in which nicotine and a strawberry additive were delivered as a vapor to male and female adolescent mice. We found that nicotine vapor alone can lead to dose-dependent CPP when using a biased design. The strawberry additive did not produce CPP on its own, and we did not observe an effect of the strawberry additive on nicotine vapor-induced reward. Neverthe...