Specific Brain Functions Research Articles

Rat intersubjective decisions are encoded by frequency-specific oscillatory contexts.

IntroductionIt is unknown how the brain coordinates decisions to withstand personal costs in order to prevent other individuals’ distress. Here we test whether local field potential (LFP) oscillations between brain regions create “neural contexts” that select specific brain functions and encode the outcomes of these types of intersubjective decisions.MethodsRats participated in an “Intersubjective Avoidance Test” (IAT) that tested rats’ willingness to enter an innately aversive chamber to prevent another rat from getting shocked. c‐Fos immunoreactivity was used to screen for brain regions involved in IAT performance. Multi‐site local field potential (LFP) recordings were collected simultaneously and bilaterally from five brain regions implicated in the c‐Fos studies while rats made decisions in the IAT. Local field potential recordings were analyzed using an elastic net penalized regression framework.ResultsRats voluntarily entered an innately aversive chamber to prevent another rat from getting shocked, and c‐Fos immunoreactivity in brain regions known to be involved in human empathy—including the anterior cingulate, insula, orbital frontal cortex, and amygdala—correlated with the magnitude of “intersubjective avoidance” each rat displayed. Local field potential recordings revealed that optimal accounts of rats’ performance in the task require specific frequencies of LFP oscillations between brain regions in addition to specific frequencies of LFP oscillations within brain regions. Alpha and low gamma coherence between spatially distributed brain regions predicts more intersubjective avoidance, while theta and high gamma coherence between a separate subset of brain regions predicts less intersubjective avoidance. Phase relationship analyses indicated that choice‐relevant coherence in the alpha range reflects information passed from the amygdala to cortical structures, while coherence in the theta range reflects information passed in the reverse direction.ConclusionThese results indicate that the frequency‐specific “neural context” surrounding brain regions involved in social cognition encodes outcomes of decisions that affect others, above and beyond signals from any set of brain regions in isolation.

Non-neurogenic SVZ-like niche in dolphins, mammals devoid of olfaction.

Adult neurogenesis has been implicated in brain plasticity and brain repair. In mammals, it is mostly restricted to specific brain regions and specific physiological functions. The function and evolutionary history of mammalian adult neurogenesis has been elusive so far. The largest neurogenic site in mammals (subventricular zone, SVZ) generates neurons destined to populate the olfactory bulb. The SVZ neurogenic activity appears to be related to the dependence of the species on olfaction since it occurs at high rates throughout life in animals strongly dependent on this function for their survival. Indeed, it dramatically decreases in humans, who do not depend so much on it. This study investigates whether the SVZ neurogenic site exists in mammals devoid of olfaction and olfactory brain structures, such as dolphins. Our results demonstate that a small SVZ-like region persists in these aquatic mammals. However, this region seems to have lost its neurogenic capabilities since neonatal stages. In addition, instead of the typical newly generated neuroblasts, some mature neurons were observed in the dolphin SVZ. Since cetaceans evolved from terrestrial ancestors, non-neurogenic SVZ may indicate extinction of adult neurogenesis in the absence of olfactory function, with the retention of an SVZ-like anatomical region either vestigial or of still unknown role.

Neuroimaging Findings Related to Behavioral Disturbances in Alzheimer's Disease: A Systematic Review.

Behavioral and psychological symptoms of dementia (BPSD) associated with Alzheimer's Disease (AD) have been linked to structural and functional alterations in fronto-temporal circuits and cortical abnormalities. However, little is known on how specific volumetric and functional brain changes may be associated with the frequency, severity and pattern of BPSD. A systematic review of the literature regarding neuroimaging and BPSD changes in AD was performed through Pubmed/Medline, ISI, and EMBASE electronic databases from January 2000 to May 2015. Eligible references (n=40) included clinical studies in which structural or functional neuroimaging assessment was performed in AD subjects presenting BPSD features. BPSD symptoms, particularly apathy and psychosis have been associated in most of studies with either volume reductions or decreased metabolism in the prefrontal cortex (orbital and dorsolateral portions), anterior cingulate, insula and temporal lobes (middle portion). WM lacunes associated with AD progression have been associated with depressive symptoms. The sum of evidence highlights the importance of BPSD-related imaging findings for the understanding of the non-cognitive symptom spectrum in AD. Results suggest that structural and functional changes in fronto-limbic areas may lead to emotional deregulation and symptom unawareness. As these findings may be present early on the AD clinical course, they may have a relevance for the development of imaging markers that could be used in diagnosis, disease monitoring and prediction of therapeutic response.

Mice that lack the C-terminal region of Reelin exhibit behavioral abnormalities related to neuropsychiatric disorders.

The secreted glycoprotein Reelin is believed to play critical roles in the pathogenesis of several neuropsychiatric disorders. The highly basic C-terminal region (CTR) of Reelin is necessary for efficient activation of its downstream signaling, and the brain structure of knock-in mice that lack the CTR (ΔC-KI mice) is impaired. Here, we performed a comprehensive behavioral test battery on ΔC-KI mice, in order to evaluate the effects of partial loss-of-function of Reelin on brain functions. The ΔC-KI mice were hyperactive and exhibited reduced anxiety-like and social behaviors. The working memory in ΔC-KI mice was impaired in a T-maze test. There was little difference in spatial reference memory, depression-like behavior, prepulse inhibition, or fear memory between ΔC-KI and wild-type mice. These results suggest that CTR-dependent Reelin functions are required for some specific normal brain functions and that ΔC-KI mice recapitulate some aspects of neuropsychiatric disorders, such as schizophrenia, bipolar disorder, and autism spectrum disorder.

Cingulo-opercular Network Efficiency Mediates the Association Between Psychotic-like Experiences and Cognitive Ability in the General Population

BackgroundPsychosis is hypothesized to occur on a spectrum between psychotic disorders and health in individuals. In the middle of the spectrum are individuals who endorse psychotic-like experiences (PLEs) that may not affect daily functioning or cause distress. Individuals with PLEs show alterations in both cognitive ability and functional connectivity of several brain networks, but the relationship among PLEs, cognition, and functional networks remains poorly understood. MethodsWe analyzed resting-state functional magnetic resonance imaging data, a range of neuropsychological tasks, and questions from the Achenbach Adult Self-Report in 468 individuals from the Human Connectome Project. We aimed to determine whether the global efficiency of specific functional brain networks supporting higher-order cognition (the frontoparietal network, cingulo-opercular network [CON], and default mode network [DMN]) was associated with PLEs and cognitive ability in a nonpsychiatric sample. ResultsA total of 21.6% of individuals in our sample endorsed at least one PLE. The PLEs were significantly negatively associated with higher-order cognitive ability, CON global efficiency, and DMN global efficiency, but not crystallized knowledge. Higher-order cognition was significantly positively associated with CON global efficiency at a significance level of p<.01. Interestingly, the association between PLEs and cognitive ability was partially mediated by CON global efficiency and, in a subset of individuals who tested negative for drugs (n = 405), the participation coefficient of the right anterior insula (a hub within the CON). ConclusionsThese findings suggest that CON integrity may represent a shared mechanism that confers risk for psychotic experiences and the cognitive deficits observed across the psychosis spectrum.

User friendliness of computer-based cognitive training for psychogeriatric patients with mild to moderate cognitive impairments

Cognitive impairment associated with dementia is characterized by a continuous decline. Cognitive training is a method to train specific brain functions such as memory and attention to prevent or slow down cognitive decline. A small number of studies has shown that cognitive training on a computer has a positive effect on both cognition and mood in people with cognitive impairment. This pilot study tested if serious games could be integrated in a psychogeriatric rehabilitation center. Fourteen psychogeriatric patients participated twice weekly in cognitive training sessions on a computer. Both the participants and the facilitator reported positive interactions and outcomes. However, after five weeks only half of the sample still participated in the training. This was partly because of patient turn-over as well as incorporating this new task in the facilitators' daily work. Fear of failure, physical limitations and rapidly decreasing cognitive function led to drop out according to the facilitator. The engagement of patients in the games and the role of the facilitator seemed essential for success, especially monitoring (and adjusting) the difficulty level of the program for every individual participant.

On the photovoltaic effect in local field potential recordings.

Optogenetics allows light activation of genetically defined cell populations and the study of their link to specific brain functions. While it is a powerful method that has revolutionized neuroscience in the last decade, the shortcomings of directly stimulating electrodes and living tissue with light have been poorly characterized. Here, we assessed the photovoltaic effects in local field potential (LFP) recordings of the mouse hippocampus. We found that light leads to several artifacts that resemble genuine LFP features in animals with no opsin expression, such as stereotyped peaks at the power spectrum, phase shifts across different recording channels, coupling between low and high oscillation frequencies, and sharp signal deflections that are detected as spikes. Further, we tested how light stimulation affected hippocampal LFP recordings in mice expressing channelrhodopsin 2 in parvalbumin neurons (PV/ChR2 mice). Genuine oscillatory activity at the frequency of light stimulation could not be separated from light-induced artifacts. In addition, light stimulation in PV/ChR2 mice led to an overall decrease in LFP power. Thus, genuine LFP changes caused by the stimulation of specific cell populations may be intermingled with spurious changes caused by photovoltaic effects. Our data suggest that care should be taken in the interpretation of electrophysiology experiments involving light stimulation.

Interfacing brain with computer to improve communication and rehabilitation after brain damage.

Communication and control of the external environment can be provided via brain-computer interfaces (BCIs) to replace a lost function in persons with severe diseases and little or no chance of recovery of motor abilities (ie, amyotrophic lateral sclerosis, brainstem stroke). BCIs allow to intentionally modulate brain activity, to train specific brain functions, and to control prosthetic devices, and thus, this technology can also improve the outcome of rehabilitation programs in persons who have suffered from a central nervous system injury (ie, stroke leading to motor or cognitive impairment). Overall, the BCI researcher is challenged to interact with people with severe disabilities and professionals in the field of neurorehabilitation. This implies a deep understanding of the disabled condition on the one hand, and it requires extensive knowledge on the physiology and function of the human brain on the other. For these reasons, a multidisciplinary approach and the continuous involvement of BCI users in the design, development, and testing of new systems are desirable. In this chapter, we will focus on noninvasive EEG-based systems and their clinical applications, highlighting crucial issues to foster BCI translation outside laboratories to eventually become a technology usable in real-life realm.

Differential responses of female and male brains to hypoxia in the marine medaka Oryzias melastigma

Hypoxia, an endocrine disruptor, affects synthesis and balance of sex steroid hormones, leading to reproductive impairment in both female and male fish. Cumulating reports demonstrated the alternation of hypothalamus-pituitary-gonad axis (HPG-axis) by hypoxia. However, the detail mechanism underlying how hypoxia may alter other brain functions remains largely unknown. In this report, we used marine medaka as a model and conducted a high-throughput RNA sequencing followed by bioinformatics analysis on hypoxia-exposed brain tissues, aiming to determine the change of transcriptional signature and to unravel the pathways that are induced by hypoxia. We found that hypoxia lead to dysregulation of brain functions (including synaptic transmission, axon guidance, potassium ion transport, neuron differentiation, and development of brain and pituitary gland), and also signaling pathways (e.g., gap junction, calcium signaling pathway, and GnRH signaling pathway). Our results further demonstrate gender-specific responses to hypoxia in female and male fish’s brains, which provides novel insights into the mechanism underlying the hypoxia induced sex specific brain functions impairments.

Probabilistic maps of the white matter tracts with known associated functions on the neonatal brain atlas: Application to evaluate longitudinal developmental trajectories in term-born and preterm-born infants

Diffusion tensor imaging (DTI) has been widely used to investigate the development of the neonatal and infant brain, and deviations related to various diseases or medical conditions like preterm birth. In this study, we created a probabilistic map of fiber pathways with known associated functions, on a published neonatal multimodal atlas. The pathways-of-interest include the superficial white matter (SWM) fibers just beneath the specific cytoarchitectonically defined cortical areas, which were difficult to evaluate with existing DTI analysis methods. The Jülich cytoarchitectonic atlas was applied to define cortical areas related to specific brain functions, and the Dynamic Programming (DP) method was applied to delineate the white matter pathways traversing through the SWM. Probabilistic maps were created for pathways related to motor, somatosensory, auditory, visual, and limbic functions, as well as major white matter tracts, such as the corpus callosum, the inferior fronto-occipital fasciculus, and the middle cerebellar peduncle, by delineating these structures in eleven healthy term-born neonates. In order to characterize maturation-related changes in diffusivity measures of these pathways, the probabilistic maps were then applied to DTIs of 49 healthy infants who were longitudinally scanned at three time-points, approximately five weeks apart. First, we investigated the normal developmental pattern based on 19 term-born infants. Next, we analyzed 30 preterm-born infants to identify developmental patterns related to preterm birth. Last, we investigated the difference in diffusion measures between these groups to evaluate the effects of preterm birth on the development of these functional pathways. Term-born and preterm-born infants both demonstrated a time-dependent decrease in diffusivity, indicating postnatal maturation in these pathways, with laterality seen in the corticospinal tract and the optic radiation. The comparison between term- and preterm-born infants indicated higher diffusivity in the preterm-born infants than in the term-born infants in three of these pathways: the body of the corpus callosum; the left inferior longitudinal fasciculus; and the pathway connecting the left primary/secondary visual cortices and the motion-sensitive area in the occipitotemporal visual cortex (V5/MT+). Probabilistic maps provided an opportunity to investigate developmental changes of each white matter pathway. Whether alterations in white matter pathways can predict functional outcomes will be further investigated in a follow-up study.

Peroxisomes in brain development and function

Peroxisomes contain numerous enzymatic activities that are important for mammalian physiology. Patients lacking either all peroxisomal functions or a single enzyme or transporter function typically develop severe neurological deficits, which originate from aberrant development of the brain, demyelination and loss of axonal integrity, neuroinflammation or other neurodegenerative processes. Whilst correlating peroxisomal properties with a compilation of pathologies observed in human patients and mouse models lacking all or individual peroxisomal functions, we discuss the importance of peroxisomal metabolites and tissue- and cell type-specific contributions to the observed brain pathologies. This enables us to deconstruct the local and systemic contribution of individual metabolic pathways to specific brain functions. We also review the recently discovered variability of pathological symptoms in cases with unexpectedly mild presentation of peroxisome biogenesis disorders. Finally, we explore the emerging evidence linking peroxisomes to more common neurological disorders such as Alzheimer's disease, autism and amyotrophic lateral sclerosis. This article is part of a Special Issue entitled: Peroxisomes edited by Ralf Erdmann.

X MARCKS the spot: myristoylated alanine-rich C kinase substrate in neuronal function and disease.

Intracellular protein-protein interactions are dynamic events requiring tightly regulated spatial and temporal checkpoints. But how are these spatial and temporal cues integrated to produce highly specific molecular response patterns? A helpful analogy to this process is that of a cellular map, one based on the fleeting localization and activity of various coordinating proteins that direct a wide array of interactions between key molecules. One such protein, myristoylated alanine-rich C-kinase substrate (MARCKS) has recently emerged as an important component of this cellular map, governing a wide variety of protein interactions in every cell type within the brain. In addition to its well-documented interactions with the actin cytoskeleton, MARCKS has been found to interact with a number of other proteins involved in processes ranging from intracellular signaling to process outgrowth. Here, we will explore these diverse interactions and their role in an array of brain-specific functions that have important implications for many neurological conditions.

Systematic Review of the Neurobiological Relevance of Chemokines to Psychiatric Disorders.

Psychiatric disorders are highly prevalent and disabling conditions of increasing public health relevance. Much recent research has focused on the role of cytokines in the pathophysiology of psychiatric disorders; however, the related family of immune proteins designated chemokines has been relatively neglected. Chemokines were originally identified as having chemotactic function on immune cells; however, recent evidence has begun to elucidate novel, brain-specific functions of these proteins of relevance to the mechanisms of psychiatric disorders. A systematic review of both human and animal literature in the PubMed and Google Scholar databases was undertaken. After application of all inclusion and exclusion criteria, 157 references were remained for the review. Some early mechanistic evidence does associate select chemokines with the neurobiological processes, including neurogenesis, modulation of the neuroinflammatory response, regulation of the hypothalamus–pituitary–adrenal axis, and modulation of neurotransmitter systems. This early evidence however does not clearly demonstrate any specificity for a certain psychiatric disorder, but is primarily relevant to mechanisms which are shared across disorders. Notable exceptions include CCL11 that has recently been shown to impair hippocampal function in aging – of distinct relevance to Alzheimer’s disease and depression in the elderly, and pre-natal exposure to CXCL8 that may disrupt early neurodevelopmental periods predisposing to schizophrenia. Pro-inflammatory chemokines, such as CCL2, CCL7, CCL8, CCL12, and CCL13, have been shown to drive chemotaxis of pro-inflammatory cells to the inflamed or injured CNS. Likewise, CX3CL has been implicated in promoting glial cells activation, pro-inflammatory cytokines secretion, expression of ICAM-1, and recruitment of CD4+ T-cells into the CNS during neuroinflammatory processes. With further translational research, chemokines may present novel diagnostic and/or therapeutic targets in psychiatric disorders.

Network effects of deep brain stimulation.

The ability to differentially alter specific brain functions via deep brain stimulation (DBS) represents a monumental advance in clinical neuroscience, as well as within medicine as a whole. Despite the efficacy of DBS in the treatment of movement disorders, for which it is often the gold-standard therapy when medical management becomes inadequate, the mechanisms through which DBS in various brain targets produces therapeutic effects is still not well understood. This limited knowledge is a barrier to improving efficacy and reducing side effects in clinical brain stimulation. A field of study related to assessing the network effects of DBS is gradually emerging that promises to reveal aspects of the underlying pathophysiology of various brain disorders and their response to DBS that will be critical to advancing the field. This review summarizes the nascent literature related to network effects of DBS measured by cerebral blood flow and metabolic imaging, functional imaging, and electrophysiology (scalp and intracranial electroencephalography and magnetoencephalography) in order to establish a framework for future studies.

Spectra of infant EEG within the first year of life: A pilot study.

Rhythmic activities in electroencephalography (EEG) have been extensively studied in adults and classic rhythms are found to correlate with specific human brain functions. However, less has been investigated in infant EEG, and EEG rhythms in infants at early ages have not been well characterized in terms of their frequency ranges. In the present pilot study, we investigated rhythmic activities in infant EEG recorded weekly from 4-8 months using high-density EEG sensor nets. The developmental changes of EEG rhythms in different frequency bands along maturation were evaluated through spectral analysis. Their longitudinal scalp maps were also studied to understand their plausible functional correlates. The present study aims to enrich the sparse knowledge about the developing patterns of EEG rhythms within the first year of life from EEG recordings of high temporal and spatial resolutions.

Leptin as a Neuroprotector and a Central Nervous System Functional Stability Factor

Adipokines are fatty tissue hormones, a relatively recently discovered class of compounds regulating energy metabolism in virtually all organs and tissues. They include leptin, discovered before and studied better than other adipokines, and evidently associated with the development of a whole series of diseases and pathological states: insulin resistance and diabetes mellitus, cardiovascular system pathology, and oncological and chronic inflammatory diseases. All these states are in one way or another mediated by the influences of leptin on the metabolism of energy substrates and the formation of a proinflammatory state. However, recent years have seen the appearance in the literature of intriguing data on fundamentally different, neurotropic, effects of leptin, suggesting that it has a direct influence on the preservation of neural structures, as well as synapse functioning and transmitter processes. These data allow leptin to be regarded as a neuroprotector, i.e., a neuroplastic factor, and possibly a significant element in realizing specific brain functions. The role of leptin deficiency in lesions to nervous structures and the establishment of the symptoms of central nervous system diseases can also be assessed from this point of view.

Current Concepts of Neurophysiological Factors in Central Regulatory Mechanism of Rapid Eye Movement Sleep: A Review.

Rapid eye movement (REM) sleep is physiologically different from the other phases of sleep. Most of the postulations by researchers have speculated on the role or significance of the REM sleep stage. Most of the proposed roles that are attributed to REM sleep in vital brain functions are still mere speculations. For example, there is no clear evidence to suggest that REM sleep may play a particular role or may mediate a proposed mechanism for a specific brain function. The aim of this review is to identify those vital processes in brain function believed to be REM sleep driven, and which have featured prominently in the works of researchers in the past. The method adopted in this review was that of information gathering from sources which included published works of past and present researchers, articles on sleep presented in seminars and conferences, published articles on sleep, lecture notes on sleep physiology, textbooks of current editions in neuroscience, reports and published works accessed from the Internet using search engines such as Google, Mamma, PubMed etc. The postulations and hypothesized roles of REM sleep in vital brain function have been clearly highlighted in this review. It is concluded from this review that neural factors involved in the central mechanisms of REM sleep are not fully understood. Nevertheless, information noted in this review lends further credence to the notion that REM sleep is crucial and probably the most important sleep phase. It is hoped that facts in the proposals and postulations chronicled in this review will serve as important information source for neuroscientists and different researchers engaged in the subject of sleep.

Fronto-parietal and cingulo-opercular network integrity and cognition in health and schizophrenia

Growing evidence suggests that coordinated activity within specific functional brain networks supports cognitive ability, and that abnormalities in brain connectivity may underlie cognitive deficits observed in neuropsychiatric diseases, such as schizophrenia. Two functional networks, the fronto-parietal network (FPN) and cingulo-opercular network (CON), are hypothesized to support top-down control of executive functioning, and have therefore emerged as potential drivers of cognitive impairment in disease-states. Graph theoretic analyses of functional connectivity data can characterize network topology, allowing the relationships between cognitive ability and network integrity to be examined. In the current study we applied graph analysis to pseudo-resting state data in 54 healthy subjects and 46 schizophrenia patients, and measured overall cognitive ability as the shared variance in performance from tasks of episodic memory, verbal memory, processing speed, goal maintenance, and visual integration. We found that, across all participants, cognitive ability was significantly positively associated with the local and global efficiency of the whole brain, FPN, and CON, but not with the efficiency of a comparison network, the auditory network. Additionally, the participation coefficient of the right anterior insula, a major hub within the CON, significantly predicted cognition, and this relationship was independent of CON global efficiency. Surprisingly, we did not observe strong evidence for group differences in any of our network metrics. These data suggest that functionally efficient task control networks support better cognitive ability in both health and schizophrenia, and that the right anterior insula may be a particularly important hub for successful cognitive performance across both health and disease.

Synthetic neuronal datasets for benchmarking directed functional connectivity metrics.

Background. Datasets consisting of synthetic neural data generated with quantifiable and controlled parameters are a valuable asset in the process of testing and validating directed functional connectivity metrics. Considering the recent debate in the neuroimaging community concerning the use of these metrics for fMRI data, synthetic datasets that emulate the BOLD signal dynamics have played a central role by supporting claims that argue in favor or against certain choices. Generative models often used in studies that simulate neuronal activity, with the aim of gaining insight into specific brain regions and functions, have different requirements from the generative models for benchmarking datasets. Even though the latter must be realistic, there is a tradeoff between realism and computational demand that needs to be contemplated and simulations that efficiently mimic the real behavior of single neurons or neuronal populations are preferred, instead of more cumbersome and marginally precise ones.Methods. This work explores how simple generative models are able to produce neuronal datasets, for benchmarking purposes, that reflect the simulated effective connectivity and, how these can be used to obtain synthetic recordings of EEG and fMRI BOLD signals. The generative models covered here are AR processes, neural mass models consisting of linear and nonlinear stochastic differential equations and populations with thousands of spiking units. Forward models for EEG consist in the simple three-shell head model while the fMRI BOLD signal is modeled with the Balloon-Windkessel model or by convolution with a hemodynamic response function.Results. The simulated datasets are tested for causality with the original spectral formulation for Granger causality. Modeled effective connectivity can be detected in the generated data for varying connection strengths and interaction delays.Discussion. All generative models produce synthetic neuronal data with detectable causal effects although the relation between modeled and detected causality varies and less biophysically realistic models offer more control in causal relations such as modeled strength and frequency location.

Immunohistochemistry and multiple labeling with antibodies from the same host species to study adult hippocampal neurogenesis.

Adult neurogenesis is a highly regulated, multi-stage process in which new neurons are generated from an activated neural stem cell via increasingly committed intermediate progenitor subtypes. Each of these subtypes expresses a set of specific molecular markers that, together with specific morphological criteria, can be used for their identification. Typically, immunofluorescent techniques are applied involving subtype-specific antibodies in combination with exo- or endogenous proliferation markers. We herein describe immunolabeling methods for the detection and quantification of all stages of adult hippocampal neurogenesis. These comprise the application of thymidine analogs, transcardial perfusion, tissue processing, heat-induced epitope retrieval, ABC immunohistochemistry, multiple indirect immunofluorescence, confocal microscopy and cell quantification. Furthermore we present a sequential multiple immunofluorescence protocol which circumvents problems usually arising from the need of using primary antibodies raised in the same host species. It allows an accurate identification of all hippocampal progenitor subtypes together with a proliferation marker within a single section. These techniques are a powerful tool to study the regulation of different progenitor subtypes in parallel, their involvement in brain pathologies and their role in specific brain functions.