eNeuro最新文献

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 prefrontal regions. Importantly, we observed behavioral deficits in rats with LC damage caused by virus injection. The latter finding highlights the importance of careful histological assessment of virus-transduced brain tissue as inadvertent damage of the targeted cell population due to virus neurotoxicity or other factors might cause unwanted side effects. Although the specific role of ACC in the flexibility of spatial behavior has not been convincingly demonstrated, our results support the beneficial role of noradrenergic transmission for an optimal function of the ACC. Overall, our findings suggest the LC exerts the projection-specific modulation of neural circuits mediating the flexibility of spatial behavior.

Older listeners often report difficulties understanding speech in noisy environments. It is important to identify where in the auditory pathway hearing-in-noise deficits arise to develop appropriate therapies. We tested how encoding of sounds is affected by masking noise at early stages of the auditory pathway by recording responses of principal cells in the anteroventral cochlear nucleus (AVCN) of aging CBA/CaJ and C57BL/6J mice in vivo. Previous work indicated that masking noise shifts the dynamic range of single auditory nerve fibers (ANFs), leading to elevated tone thresholds. We hypothesized that such threshold shifts could contribute to increased hearing-in-noise deficits with age if susceptibility to masking increased in AVCN units. We tested this by recording the responses of AVCN principal neurons to tones in the presence and absence of masking noise. Surprisingly, we found that masker-induced threshold shifts decreased with age in primary-like units and did not change in choppers. In addition, spontaneous activity decreased in primary-like and chopper units of old mice, with no change in dynamic range or tuning precision. In C57 mice, which undergo early-onset hearing loss, units showed similar changes in threshold and spontaneous rate at younger ages, suggesting they were related to hearing loss and not simply aging. These findings suggest that sound information carried by AVCN principal cells remains largely unchanged with age. Therefore, hearing-in-noise deficits may result from other changes during aging, such as distorted across-channel input from the cochlea and changes in sound coding at later stages of the auditory pathway.

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. The reward positivity peaked ∼230 ms with a maximal at channel FCz (M = -0.695 μV, ±0.23) and was significantly different than zero (p < 0.01). Participants took ∼3.38 s to reach the goal location and exhibited a general lose-shift (68.3% ±3.5) response strategy and posterror slowing. Overall, these novel findings provide support for the idea that combining mobile-EEG with augmented reality technology is a feasible solution to enhance the ecological validity of human electrophysiological studies of goal-directed behavior and a step toward a new era of human cognitive neuroscience research that blurs the line between laboratory and reality.

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 target code in the motor response. Further, when SUs were separated into regular/fast spiking neurons, these cell types showed different spatial code progressions during the late delay period, only converging toward gaze coding during the final saccade motor response. Finally, reconstructing MU populations (by summing SU data within the same sites) failed to replicate either the SU or MU pattern. These results confirm the theoretical and practical potential of MU activity recordings as a biomarker for fundamental sensorimotor transformations (e.g., target-to-gaze coding in the oculomotor system), while also highlighting the importance of SU activity for coding more subtle (e.g., predictive/memory) aspects of sensorimotor behavior.

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 double and single stimulation groups compared with that in sham. No differences in mathematical accuracy were observed. Our results confirm the pivotal role of the FPN in WM and suggest its functional dissociation, with the frontal component more implicated in the retrieval stage and the parietal component in the processing and retention stages.

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 within the neuronal network. Moreover, it appears that the component frequencies of the more complex patterns are stored in different populations of neurons and neuron subtypes.

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-pattern-selective neural dynamics distinguished whether the incoming choice was a repetition or a switch from the previous choice before a response choice. Other neural dynamics was selective to outcome and increased within-trial activity following response. Our results demonstrate how the concatenated ensembles of M2 and DS process distinct features of decision-related signals at various points in time. Thereby, the M2 and DS collaboratively monitor action outcomes and determine the subsequent choice, whether to repeat or switch, for action selection.

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 of cAMP formation but abolished the ability of postsynaptic mGlu3 receptors to boost mGlu5 receptor-mediated inositol phospholipid hydrolysis in PFC slices. Remarkably, activation of presynaptic mGlu2/3 receptors did not inhibit but rather amplified depolarization-induced [³H]-D-aspartate release in synaptosomes prepared from the PFC of methamphetamine-treated mice. These findings demonstrate that exposure to methamphetamine causes changes in the expression and function of mGlu2 and mGlu3 receptors, which might alter excitatory synaptic transmission in the PFC and raise the attractive possibility that selective inhibitors of mGlu2 or mGlu3 receptors (or both) may be used to improve cognitive dysfunction in individuals affected by MUD.