Decoding working memory information from neurons with and without persistent activity in the primate prefrontal cortex.

Persistent activity of neurons in the prefrontal cortex has been thought to represent the information maintained in working memory, though alternative models have challenged this idea. Theories that depend on the dynamic representation of information posit that stimulus information may be maintained by the activity pattern of neurons whose firing rate is not significantly elevated above their baseline during the delay period of working memory tasks. We thus tested the ability of neurons that do and do not generate persistent activity in the prefrontal cortex of monkeys to represent spatial and object information in working memory. Neurons that generated persistent activity represented more information about the stimuli in both spatial and object working memory tasks. The amount of information that could be decoded from neural activity depended on the choice of decoder and parameters used but neurons with persistent activity outperformed non-persistent neurons consistently. Averaged across all neurons and stimuli, the firing rate did not appear clearly elevated above baseline during the maintenance of neural activity particularly for object working memory; however, this grand average masked neurons that generated persistent activity selective for their preferred stimuli, which carried the majority of stimulus information. These results reveal that prefrontal neurons that generate persistent activity maintain information more reliably during working memory.NEW & NOTEWORTHY Competing theories suggest that neurons that generate persistent activity or do not are primarily responsible for the maintenance of information, particularly regarding object working memory. Although the two models have been debated on theoretical terms, direct comparison of empirical results has been lacking. Analysis of neural activity in a large database of prefrontal recordings revealed that neurons that generate persistent activity were primarily responsible for the maintenance of both spatial and object working memory.

Local organization of spatial and shape information during working memory in the primate prefrontal cortex.

While the current understanding of sensory and motor cortical areas has been defined topographical maps across the surface of these areas, higher cortical areas, such as the prefrontal cortex, seem to lack an equivalent organization, with only limited evidence of functional clustering of neurons with similar stimulus properties. We sought to examine whether neurons that represent similar spatial and object information are clustered in the monkey prefrontal cortex and whether such an organization only emerges as a result of training. We analyzed neurophysiological recordings from male macaque monkeys before and after they were trained to perform cognitive tasks. Neurons with similar spatial or shape selectivity were more likely than chance to be encountered at short distances from each other. This pattern of organization was present even in naïve animals, prior to any cognitive training. Our results reveal that prefrontal microstructure automatically supports orderly representations of spatial and object information.

Decoding working memory information from persistent and activity-silent neurons in the primate prefrontal cortex.

Persistent activity of neurons in the prefrontal cortex has been thought to represent the information maintained in working memory, though alternative models have recently challenged this idea. Activity-silent theories posit that stimulus information may be maintained by the activity pattern of neurons that do not produce firing rate significantly elevated about their baseline during the delay period of working memory tasks. We thus tested the ability of neurons that do and do not generate persistent activity in the prefrontal cortex of monkeys to represent spatial and object information in working memory. Neurons that generated persistent activity represented more information about the stimuli in both spatial and object working memory tasks. The amount of information that could be decoded from neural activity depended on the choice of decoder and parameters used but neurons with persistent activity outperformed non-persistent neurons consistently. Although averaged across all neurons and stimuli, firing rate did not appear clearly elevated above baseline during the maintenance of neural activity particularly for object working memory, this grant average masked neurons that generated persistent activity selective for their preferred stimuli, which carried the majority of information about the stimulus identity. These results reveal that prefrontal neurons with generate persistent activity constitute the primary mechanism of working memory maintenance in the cortex. NEW AND NOTEWORTHY: Competing theories suggest that neurons that generate persistent activity or do not are primarily responsible for the maintenance of information, particularly regarding object working memory. While the two models have been debated on theoretical terms, direct comparison of empirical results have been lacking. Analysis of neural activity in a large database of prefrontal recordings revealed that neurons that generate persistent activity were primarily responsible for the maintenance of both spatial and object working memory.

More Prominent Nonlinear Mixed Selectivity in the Dorsolateral Prefrontal than Posterior Parietal Cortex.

Neurons in the dorsolateral prefrontal cortex (dlPFC) and posterior parietal cortex (PPC) are activated by different cognitive tasks and respond differently to the same stimuli depending on task. The conjunctive representations of multiple tasks in nonlinear fashion in single neuron activity, is known as nonlinear mixed selectivity (NMS). Here, we compared NMS in a working memory task in areas 8a and 46 of the dlPFC and 7a and lateral intraparietal cortex (LIP) of the PPC in macaque monkeys. NMS neurons were more frequent in dlPFC than in PPC and this was attributed to more cells gaining selectivity in the course of a trial. Additionally, in our task, the subjects' behavioral performance improved within a behavioral session as they learned the session-specific statistics of the task. The magnitude of NMS in the dlPFC also increased as a function of time within a single session. On the other hand, we observed minimal rotation of population responses and no appreciable differences in NMS between correct and error trials in either area. Our results provide direct evidence demonstrating a specialization in NMS between dlPFC and PPC and reveal mechanisms of neural selectivity in areas recruited in working memory tasks.

Effects of different N-acyl-serine lactone signaling molecules on the performance of anaerobic granular sludge.

Exogenous addition of acyl-homoserine lactone (AHL) signaling molecules can improve or inhibit the methane production performance of anaerobic granular sludge (AnGS) by quorum sensing (QS). To explore the specific effect of AHLs on AnGS, 2 µM of signal molecules were added to the reactor and we analyzed their effects on AnGS biodiversity, extracellular polymeric substance (EPS), specific methanogenic activity (SMA) and chemical oxygen demand (COD) removal rate of AnGS. The results indicated that the four types of AHLs improve the COD removal rate, SMA and organic composition of AnGS. The addition of N-(ß-ketocaproyl)-dl-homoserine lactone (3O-C6-HSL) yielded the greatest increase in methanogenic activity, reaching a maximum of 30.83%. The four types of AHLs stimulate the secretion of EPS in AnGS by group sensing regulation. The addition of N-hexanoyl-l-homoserine lactone (C6-HSL), N-octanoyl-dl-lactone (C8-HSL) and 3O-C6-HSL induced the enrichment of Actinobacteria. Thus, the process of hydrolysis and acidification of AnGS is accelerated. The addition of N-butyryl-dl-homoserine lactone (C4-HSL), C6-HSL and 3O-C6-HSL promote the potential methanogenic metabolic pathway of AnGS. The addition of all AHLs directly or indirectly enhanced the methane metabolism pathway of sludge and improved the specific methane generation activity of AnGS. These results are expected to provide preliminary research data for enhancing the methane production efficiency of reactors and enriching the biological activity of AnGS.

Sludge Derived Carbon Modified Anode in Microbial Fuel Cell for Performance Improvement and Microbial Community Dynamics.

The conversion of activated sludge into high value-added materials, such as sludge carbon (SC), has attracted increasing attention because of its potential for various applications. In this study, the effect of SC carbonized at temperatures of 600, 800, 1000, and 1200 °C on the anode performance of microbial fuel cells and its mechanism are discussed. A pyrolysis temperature of 1000 °C for the loaded electrode (SC1000/CC) generated a maximum areal power density of 2.165 ± 0.021 W·m-2 and a current density of 5.985 ± 0.015 A·m-2, which is 3.017- and 2.992-fold that of the CC anode. The addition of SC improves microbial activity, optimizes microbial community structure, promotes the expression of c-type cytochromes, and is conducive to the formation of electroactive biofilms. This study not only describes a technique for the preparation of high-performance and low-cost anodes, but also sheds some light on the rational utilization of waste resources such as aerobic activated sludge.

Study on the mechanism of inhibiting the calcification of anaerobic granular sludge induced by the addition of trace signal molecule (3O-C6-HSL).

Microbiota quorum sensing (QS) induced by 3O-C6-HSL (N-(ß-ketocaproyl)-DL-homoserine lactone) inhibited the calcification of anaerobic granular sludge (AnGS), and the mechanism of promoting the activity recovery of calcified AnGS was studied in this paper. Through research, it was speculated that 3O-C6-HSL acted on calcified AnGS residual microorganisms to trigger QS. It enriched many functional microorganisms. For example, it promoted the growth of Methanospirillum. The CO2 could be consumed quickly by Methanospirillum and reduced the calcium carbonate formation. The increase of microbial biomass would promote the activity of sludge. What's more, the pore size and porosity of sludge would increase, so the mass transfer channel will be broadened at same time. All those, could help the calcified AnGS quickly restore the activity and anaerobic system recover normal, which provided a new idea for the emergency rescue of anaerobic system in the future.

Emergence of Nonlinear Mixed Selectivity in Prefrontal Cortex after Training.

Neurons in the PFC are typically activated by different cognitive tasks, and also by different stimuli and abstract variables within these tasks. A single neuron's selectivity for a given stimulus dimension often changes depending on its context, a phenomenon known as nonlinear mixed selectivity (NMS). It has previously been hypothesized that NMS emerges as a result of training to perform tasks in different contexts. We tested this hypothesis directly by examining the neuronal responses of different PFC areas before and after male monkeys were trained to perform different working memory tasks involving visual stimulus locations and/or shapes. We found that training induces a modest increase in the proportion of PFC neurons with NMS exclusively for spatial working memory, but not for shape working memory tasks, with area 9/46 undergoing the most significant increase in NMS cell proportion. We also found that increased working memory task complexity, in the form of simultaneously storing location and shape combinations, does not increase the degree of NMS for stimulus shape with other task variables. Lastly, in contrast to the previous studies, we did not find evidence that NMS is predictive of task performance. Our results thus provide critical insights on the representation of stimuli and task information in neuronal populations, in working memory.SIGNIFICANCE STATEMENT How multiple types of information are represented in working memory remains a complex computational problem. It has been hypothesized that nonlinear mixed selectivity allows neurons to efficiently encode multiple stimuli in different contexts, after subjects have been trained in complex tasks. Our analysis of prefrontal recordings obtained before and after training monkeys to perform working memory tasks only partially agreed with this prediction, in that nonlinear mixed selectivity emerged for spatial but not shape information, and mostly in mid-dorsal PFC. Nonlinear mixed selectivity also displayed little modulation across either task complexity or correct performance. These results point to other mechanisms, in addition to nonlinear mixed selectivity, representing complex information about stimulus and task context in neuronal activity.

Improvement in calcified anaerobic granular sludge performance by exogenous acyl-homoserine lactones.

Given the high content of Ca2+ in waste paper recycling wastewater, the anaerobic granular sludge (AnGS) undergoes calcification during wastewater treatment and affects the treatment efficiency. To restore the activity of calcified AnGS and improve the performance of AnGS, four types of N-acyl-homoserine lactones (AHLs) were added to the AnGS system while papermaking wastewater treatment. The addition of N-butyryl-DL-homoserine lactone(C4-HSL) and N-octanoyl-DL-homoserine lactone (C8-HSL) had an inhibitory affect the COD removal efficiency and SMA of sludge at the inception. The addition of N-hexanoyl-L-homoserine lactone (C6-HSL) has no obvious effect on the COD removal efficiency, but can improve the SMA of sludge more obviously. The addition of N-(ß-ketocaproyl)-DL-homoserine lactone (3O-C6-HSL) can increased COD removal efficiency and promoted SMA together obviously. The addition of C6-HSL and 3O-C6-HSL can increase volatile suspended solid (VSS)/total suspended solid (TSS), and regulate extracellular polymeric substance (EPS) secretion in AnGS. Analysis of microbial sequencing revealed changes in the microbial community structure following AHL addition, which enhanced the methane metabolism pathway in sludge. The addition of C6-HSL, C8-HSL, and 3O-C6-HSL increased Methanosaeta population, thus increasing the aceticlastic pathway in sludge. Thus, exogenous AHLs can play an important role in regulating microbial community structure, and in improving the performance of AnGS.

Ultrastructure of geniculocortical synaptic connections in the tree shrew striate cortex.

To determine whether thalamocortical synaptic circuits differ across cortical areas, we examined the ultrastructure of geniculocortical terminals in the tree shrew striate cortex to compare directly the characteristics of these terminals with those of pulvinocortical terminals (examined previously in the temporal cortex of the same species; Chomsung et al. [] Cereb Cortex 20:997-1011). Tree shrews are considered to represent a prototype of early prosimian primates but are unique in that sublaminae of striate cortex layer IV respond preferentially to light onset (IVa) or offset (IVb). We examined geniculocortical inputs to these two sublayers labeled by tracer or virus injections or an antibody against the type 2 vesicular glutamate antibody (vGLUT2). We found that layer IV geniculocortical terminals, as well as their postsynaptic targets, were significantly larger than pulvinocortical terminals and their postsynaptic targets. In addition, we found that 9-10% of geniculocortical terminals in each sublamina contacted GABAergic interneurons, whereas pulvinocortical terminals were not found to contact any interneurons. Moreover, we found that the majority of geniculocortical terminals in both IVa and IVb contained dendritic protrusions, whereas pulvinocortical terminals do not contain these structures. Finally, we found that synaptopodin, a protein uniquely associated with the spine apparatus, and telencephalin (TLCN, or intercellular adhesion molecule type 5), a protein associated with maturation of dendritic spines, are largely excluded from geniculocortical recipient layers of the striate cortex. Together our results suggest major differences in the synaptic organization of thalamocortical pathways in striate and extrastriate areas.

Contribution of the spinal cord BDNF to the development of neuropathic pain by activation of the NR2B-containing NMDA receptors in rats with spinal nerve ligation.

The NMDA receptor and the brain-derived neurotrophic factor (BDNF) are involved in central sensitization and synaptic plasticity in the spinal cord. To determine whether the spinal cord BDNF contributes to the development and maintenance of neuropathic pain by activation of the dorsal horn NR2B-containing NMDA (NMDA-2B) receptors, this study was designed to investigate if alterations in BDNF and its TrkB receptor in the spinal dorsal horn would parallel the timeline of the development of neuropathic pain in lumbar 5 (L5) spinal nerve ligated (SNL) rats. The enzyme-linked immunosorbent assay (ELISA) showed that the BDNF concentration significantly increased during 24 h post-surgery, and the maximal enhancement lasted for 48 h. It declined as time progressed and returned to the level of pre-operation at 28 days after SNL. In parallel with the alteration of BDNF concentration in the spinal dorsal horn, the 50% paw withdrawal threshold (PWT) of the ipsilateral hind paw in SNL rats also showed a significant decrease during 24-48 h after SNL as compared with those in sham-operated rats. The correlation analysis revealed that the BDNF concentration had a negative correlation with 50% PWT in early stage (0-48 h) (r=-0.974, p=0.001), but not late stage (3-28 days) (r=0.3395, p=0.6605), after SNL. Similarly, the immunohistochemical staining revealed that a significant up-regulation of BDNF expression in the spinal dorsal horn appeared as early as 12 h post-operation in SNL rats, peaked at 24-48 h, declined at 3 days and disappeared at 14 days after SNL. In contrast, an increase in NMDA-2B receptors expression in the spinal dorsal horn was delayed to 48 h after SNL. The increase reached peak at 3 days, lasted for 14 days, and returned to the control level of pre-operation at 28 days after SNL. The maximal enhancement of BDNF expression occurred in early stage (24-48 h) after nerve injury, while the peak of NMDA-2B receptors expression appeared in late stage (3-14 days) post-nerve ligation. As compared with the dynamic changes of 50% PWT in the timeline after nerve injury, the maximal enhancement of BDNF expression closely paralleled the maximal decline in the slope of 50% PWT, while the peak of NMDA-2B receptors expression corresponded with the plateau of the decreased 50% PWT. Therefore, the increased BDNF in the spinal dorsal horn was likely to be associated with the initiation of neuropathic pain in early stage (0-48 h), while the activation of NMDA-2B receptors was involved in the maintenance of persistent pain states in late stage (2-14 days) after nerve injury. Moreover, the present study also demonstrated that the BDNF/TrkB-mediated signaling pathway within the spinal cord might be involved in the induction of neuropathic pain in early stage after nerve injury, and the selective NMDA-2B receptors antagonist (Ro 25-6981) almost completely blocked the BDNF-induced mechanical allodynia in all of the tested rats. These data suggested that the BDNF/TrkB-mediated signaling pathway in the spinal cord was involved in the development of nerve injury-induced neuropathic pain through the activation of dorsal horn NMDA-2B receptors.