Specialized prefrontal “auditory fields”: organization of primate prefrontal-temporal pathways

No other modality is more frequently represented in the prefrontal cortex than the auditory, but the role of auditory information in prefrontal functions is not well understood. Pathways from auditory association cortices reach distinct sites in the lateral, orbital, and medial surfaces of the prefrontal cortex in rhesus monkeys. Among prefrontal areas, frontopolar area 10 has the densest interconnections with auditory association areas, spanning a large antero-posterior extent of the superior temporal gyrus from the temporal pole to auditory parabelt and belt regions. Moreover, auditory pathways make up the largest component of the extrinsic connections of area 10, suggesting a special relationship with the auditory modality. Here we review anatomic evidence showing that frontopolar area 10 is indeed the main frontal “auditory field” as the major recipient of auditory input in the frontal lobe and chief source of output to auditory cortices. Area 10 is thought to be the functional node for the most complex cognitive tasks of multitasking and keeping track of information for future decisions. These patterns suggest that the auditory association links of area 10 are critical for complex cognition. The first part of this review focuses on the organization of prefrontal-auditory pathways at the level of the system and the synapse, with a particular emphasis on area 10. Then we explore ideas on how the elusive role of area 10 in complex cognition may be related to the specialized relationship with auditory association cortices

Extracellular vesicles derived from bone marrow mesenchymal stem cells enhance myelin maintenance after cortical injury in aged rhesus monkeys

Cortical injury, such as stroke, causes neurotoxic cascades that lead to rapid death and/or damage to neurons and glia. Axonal and myelin damage in particular, are critical factors that lead to neuronal dysfunction and impair recovery of function after injury. These factors can be exacerbated in the aged brain where white matter damage is prevalent. Therapies that can ameliorate myelin damage and promote repair by targeting oligodendroglia, the cells that produce and maintain myelin, may facilitate recovery after injury, especially in the aged brain where these processes are already compromised. We previously reported that a novel therapeutic, Mesenchymal Stem Cell derived extracellular vesicles (MSC-EVs), administered intravenously at both 24 h and 14 days after cortical injury, reduced microgliosis (Go et al. 2019), reduced neuronal pathology (Medalla et al. 2020), and improved motor recovery (Moore et al. 2019) in aged female rhesus monkeys. Here, we evaluated the effect of MSC-EV treatment on changes in oligodendrocyte maturation and associated myelin markers in the sublesional white matter using immunohistochemistry, confocal microscopy, stereology, qRT-PCR, and ELISA. Compared to vehicle control monkeys, EV-treated monkeys showed a reduction in the density of damaged oligodendrocytes. Further, EV-treatment was associated with enhanced myelin maintenance, evidenced by upregulation of myelin-related genes and increases in actively myelinating oligodendrocytes in sublesional white matter. These changes in myelination correlate with the rate of motor recovery, suggesting that improved myelin maintenance facilitates this recovery. Overall, our results suggest that EVs act on oligodendrocytes to support myelination and improves functional recovery after injury in the aged brain. SIGNIFICANCE: We previously reported that EVs facilitate recovery of function after cortical injury in the aged monkey brain, while also reducing neuronal pathology (Medalla et al. 2020) and microgliosis (Go et al. 2019). However, the effect of injury and EVs on oligodendrocytes and myelination has not been characterized in the primate brain (Dewar et al. 1999; Sozmen et al. 2012; Zhang et al. 2013). In the present study, we assessed changes in myelination after cortical injury in aged monkeys. Our results show, for the first time, that MSC-EVs support recovery of function after cortical injury by enhancing myelin maintenance in the aged primate brain

Non-linear dimensionality reduction on extracellular waveforms reveals cell type diversity in premotor cortex

Cortical circuits are thought to contain a large number of cell types that coordinate to produce behavior. Current in vivo methods rely on clustering of specified features of extracellular waveforms to identify putative cell types, but these capture only a small amount of variation. Here, we develop a new method (WaveMAP) that combines non-linear dimensionality reduction with graph clustering to identify putative cell types. We apply WaveMAP to extracellular waveforms recorded from dorsal premotor cortex of macaque monkeys performing a decision-making task. Using WaveMAP, we robustly establish eight waveform clusters and show that these clusters recapitulate previously identified narrow- and broad-spiking types while revealing previously unknown diversity within these subtypes. The eight clusters exhibited distinct laminar distributions, characteristic firing rate patterns, and decision-related dynamics. Such insights were weaker when using feature-based approaches. WaveMAP therefore provides a more nuanced understanding of the dynamics of cell types in cortical circuits.https://elifesciences.org/articles/67490Published versio

Inhibition of colony stimulating factor 1 receptor corrects maternal inflammation-induced microglial and synaptic dysfunction and behavioral abnormalities

Abstract Maternal immune activation (MIA) disrupts the central innate immune system during a critical neurodevelopmental period. Microglia are primary innate immune cells in the brain although their direct influence on the MIA phenotype is largely unknown. Here we show that MIA alters microglial gene expression with upregulation of cellular protrusion/neuritogenic pathways, concurrently causing repetitive behavior, social deficits, and synaptic dysfunction to layer V intrinsically bursting pyramidal neurons in the prefrontal cortex of mice. MIA increases plastic dendritic spines of the intrinsically bursting neurons and their interaction with hyper-ramified microglia. Treating MIA offspring by colony stimulating factor 1 receptor inhibitors induces depletion and repopulation of microglia, and corrects protein expression of the newly identified MIA-associated neuritogenic molecules in microglia, which coalesces with correction of MIA-associated synaptic, neurophysiological, and behavioral abnormalities. Our study demonstrates that maternal immune insults perturb microglial phenotypes and influence neuronal functions throughout adulthood, and reveals a potent effect of colony stimulating factor 1 receptor inhibitors on the correction of MIA-associated microglial, synaptic, and neurobehavioral dysfunctions

Los avatares de la identidad de la mujer en tres obras chilenas de la postdictadura: 'Nosotras que nos queremos tanto', 'La muerte y la doncella' y 'La hija del General'

This doctoral dissertation is a study of three works: Marcela Serrano’s novel We Who Love Us So Much (1992), Ariel Dorfman’s play Death and the Maiden (1992) and its filmic version directed by Roman Polanski, and the documentary directed by Maria Elena Wood, The General’s Daughter (2006). Through the representations of subjectivist female characters in the works, we analyze what we call the vicissitudes of female identity in relation to the agitated sociopolitical circumstances that Chile lived from the sixties to 2006. In those decades, we observe the process of the construction of a revolutionary identity that culminates with the election of the Popular Unity government (1970-1973). Then, we examine the breakdown of female revolutionary identity during the violent repression known as the military dictatorship (1973-1990) after the coup d’état. Finally, we investigate the reconstitution of the identity of the women on the political left, a process assumed independently (rather than collectively) by women of varied characteristics and political orientations during the re-democratization period and until 2006. By analysing the female characters moving in literature, theatre, and film, we observe that these characterizations have helped to inform the readers/viewers through sharing stories of women, their limitations, their personal and collective visions presenting their doubts and fears on matters pertaining to them as female entities. But the greatest finding in this study is to discover that cultural products contain a number of female characters that can overcome their limitations in fiction, as is the case for women working in public spaces such as Michelle Bachelet, a “historical character” from The General's Daughter. They are firmly committed to the reality of women’s lives in Chile and deliver an optimistic message; women must continue integrating other women in order to end the discrimination that still exists in Chile

A descriptive study on classroom management in selected public and private preschools in Makati

This is a descriptive study on classroom management in public and private preschools in Makati. The study focuses on the three components of classroom management namely, establishing an environment for learning, organizing and managing work time, and coping with challenges. This inquiry examined six random private and public schools preschools in Makati. The participants were 18 preschool teachers, 3 teacher participants from each preschool. The participants had at least 3 years of teaching experience in the current school. Surveys with open-ended questions were utilized to gather data for this study. Subsequently, simple tallying, evaluation and the point system were used to analyze the data gathered. The results of the study described the classroom management strategies that are being utilized by private and public preschool teachers in Makati. The private and public schools showed positive results regarding their classroom management practices, however, public preschools showed a more dismal outcome resulting to a less productive classroom management approach because of lack of funding and manpower. The results of the study will benefit the early childhood practices and the educators as well