Exploring undiscovered public knowledge in neuroscience.

In this essay, I argue that the combination of research synthesis and philosophical methods can fill an important methodological gap in neuroscience. While experimental research and formal modelling have seen their methods progressively increase in rigour and sophistication over the years, the task of analysing and synthesizing the vast literature reporting new results and models has lagged behind. The problem is aggravated because neuroscience has grown and expanded into a vast mosaic of related but partially independent subfields, each with their own literatures. This fragmentation not only makes it difficult to see the full picture emerging from neuroscience research but also limits progress in individual subfields. The current neuroscience literature has the perfect conditions to create what the information scientist Don Swanson called "undiscovered public knowledge"-knowledge that exists in the mutual implications of different published pieces of information but that is nonetheless undiscovered because those pieces have not been explicitly connected. Current methods for rigorous research synthesis, such as systematic reviews and meta-analyses, mostly focus on combining similar studies and are not suited for exploring undiscovered public knowledge. To that aim, they need to be adapted and supplemented. I argue that successful exploration of the hidden implications in the neuroscience literature will require the combination of these adapted research synthesis methods with philosophical methods for rigorous (and creative) analysis and synthesis.

Writing Papers to Be Memorable, Even When They Are Not Really Read.

This paper discusses how our bad reading habits are starting to influence how we write. This short abstract and the picture next to it summarize the arguments in this paper. Just kidding, they do not. One really needs to read the paper for that.

To Read More Papers, or to Read Papers Better? A Crucial Point for the Reproducibility Crisis.

The overflow of scientific literature stimulates poor reading habits which can aggravate science's reproducibility crisis. Thus, solving the reproducibility crisis demands not only methodological changes, but also changes in our relationship with the scientific literature, especially our reading habits. Importantly, this does not mean reading more, it means reading better.

How the Hippocampus Represents Memories: Making Sense of Memory Allocation Studies.

In recent years there has been a wealth of studies investigating how memories are allocated in the hippocampus. Some of those studies showed that it is possible to manipulate the identity of neurons recruited to represent a given memory without affecting the memory's behavioral expression. Those findings raised questions about how the hippocampus represents memories, with some researchers arguing that hippocampal neurons do not represent fixed stimuli. Herein, an alternative hypothesis is argued. Neurons in high-order brain regions can be tuned to multiple dimensions, forming complex, abstract representations. It is argued that such complex receptive fields allow those neurons to show some flexibility in their responses while still representing relatively fixed sets of stimuli. Moreover, it is pointed out that changes induced by artificial manipulation of cell assemblies are not completely redundant-the observed behavioral redundancy does not imply cognitive redundancy, as different, but similar, memories may induce the same behavior.

Isolating the key factors defining the magnitude of hippocampal neurogenesis' effects on anxiety, memory and pattern separation.

In this paper, I analyze the hypothesis that hippocampal neurogenesis (HN) exerts its effects on behavior via activation of inhibitory circuits in the hippocampus. Using a very simple mathematical model (half-borrowed from biochemistry) to aid the reasoning, I show that the key factors determining the magnitude of HN's effects on behavior are: the baseline levels of HN in the animal, the efficiency of the animal's inhibitory circuits, the strength/intensity of the stimulus presented to the animal and how much accuracy the behavioral task requires from the information contained in the hippocampal representations. Taken together, those factors can help explain patterns observed in the behavioral results for memory, pattern separation and anxiety. The conclusions of the analysis suggest that HN's effects on inhibitory circuits can explain the impact of neurogenesis on both emotion and cognition and provide a framework to interpret future studies about the effects of HN on different behaviors, with animals of different ages and of different species.

The evolutionary significance of hippocampal neurogenesis.

Hippocampal neurogenesis (HN) has been implicated in a variety of hippocampus-dependent behaviors in the laboratory but its evolutionary significance is still debated. Some authors have argued that HN is an adaptation while others argued it is an atavism. However, recent analyses lead to the conclusion that HN likely evolved concurrently with the dentate gyrus itself, both being dependent on a migration of neural stem and progenitor cells out of the periventricular zone that occurs during development. This may render the previous debates obsolete, as selective pressure was likely acting upon the mammalian dentate gyrus itself, with neurogenesis being a mere spandrel in dentate gyrus' evolution.

Plasticity and redundancy in the integration of adult born neurons in the hippocampus.

Hippocampal neurogenesis (HN) is an extreme form of plasticity that inevitably rewires the hippocampal circuit and this rewiring was put forward as a possible mechanism for neurogenesis' behavioral effects. Here, I critically evaluate multiple lines of evidence to argue that structural plasticity induced by HN is, to a large extent, functionally redundant and thus has limited impact on behavior. The associative plasticity rules along with properties of immature neurons should only allow the survival of new neurons whose pre and postsynaptic partners have correlated activity, leading to functional redundancy. Moreover, non-redundant rewiring, even with its computational benefits, would impair meaningful communication between the hippocampus and other brain regions. This implies that associative plasticity rules constrain structural plasticity induced by neurogenesis, allowing the brain to balance plasticity and stability to maintain proper functioning. It also implies that behavioral effects of HN are mediated by other mechanisms apart from circuit rewiring.

Hippocampal neurogenesis and pattern separation: A meta-analysis of behavioral data.

The generation of new neurons in the hippocampus of adult mammals has become a widely accepted phenomenon, but the functional significance of the adult neurogenesis in the hippocampus is not fully understood. One of the main hypotheses currently investigated suggests that neurogenesis contributes to pattern separation in the dentate gyrus. Many behavioral studies were conducted aiming to test this hypothesis using rodents as animal model. In those studies, researches ablated neurogenesis in the animals and subsequently evaluate them in tests of behavioral pattern separation, that is, behaviors that are thought to rely on the computational process of pattern separation. The results of these studies are varied, with most supporting a role for neurogenesis in pattern separation, but some others not. To address this controversy we performed a systematic review and meta-analysis of studies evaluating the effect of neurogenesis ablation on behavioral pattern separation. Analysis results indicated that most of the literature in the topic is surprisingly consistent and, although there are two studies with divergent results, the bulk of the literature supports an effect of hippocampal neurogenesis on behavioral pattern separation. We discuss those findings in light of other behavioral effects of hippocampal neurogenesis ablation, limitations of behavioral data and other lines of evidence about the effect of hippocampal neurogenesis in the dentate gyrus.

Reappraising the role of dopamine in adolescent risk-taking behavior.

Adolescence is characterized by increased risk-taking, which is often ascribed to developmental changes in dopaminergic signaling. Popular models propose that these behaviors are caused by dopamine-induced hypersensitivity to rewards, which overrides adolescents' immature self-control mechanisms. However, these models are often based on oversimplified notions about the workings and functions of dopamine. Here we discuss the relationship between changes in the dopaminergic system and adolescent behavior in light of current theories/models about the functions of dopamine. We show that dopamine is linked to learning, adaptive decision-making under uncertainty, and increased motivation to work for rewards. Thus, changes in the dopaminergic system contribute to the maturation of cognitive control through various mechanisms, contrary to the false dichotomy between reward processing and self-control. Finally, we note that dopamine interacts with a number of other neuromodulator systems, which also change during adolescence, but that have been largely ignored in the field of adolescent development. A full understanding of adolescent behavior will require these neurochemicals and their interactions with dopamine to be taken into account.

Sex-specific association between urinary kisspeptin and pubertal development.

Kisspeptins play a crucial role during pubertal development, but little is known about how their peripheral concentrations relate to sexual maturation. This is partly due to the lack of non-invasive, quick, and reliable peripheral kisspeptin measures, which limit widespread testing. Here, we investigated the relationship between kisspeptin concentrations measured from midstream urine samples with 2-h retention periods and developmental markers (age, self-reported pubertal status, and saliva concentrations of testosterone and DHEA sulphate ) in 209 typically developing 9- to 15-year-old males and females. As a result of the study, we found marked sex differences. Kisspeptin concentrations were similar between sexes until around 12 years of age, but, thereafter, kisspeptin concentrations in females did not change significantly, whereas, in males, there was a clear positive correlation with developmental measures. Our results replicate previous findings regarding kisspeptin concentration changes across the pubertal transition obtained from blood samples, suggesting that measuring these peptides in urine has the potential for exploring kisspeptins' peripheral effects and their associations with pubertal status.

Hippocampal place cells are topographically organized, but physical space has nothing to do with it.

Topographical organization can be found in many areas of the cerebral cortex, although its presence in higher order cortices is debated. Some studies evaluated whether this pattern of organization is present in the hippocampus, trying to determine whether hippocampal place cells are organized around a topographical map of space. Those studies indicated that the topographical organization of hippocampal place cells is either very limited or simply nonexistent. In this paper, we argue for a different interpretation of available evidence and suggest that there is a topographical organization in hippocampal place cells, but the topographical map formed is not a map of the physical space. Although place cell firing is correlated with the animal's position and is important to spatial navigation, place cells encode much more information than just location. Thus, we should not expect the topographical map to be organized around physical space, but around an abstract, multidimensional space containing the receptive fields of place cells. We show that this conclusion is supported by two of the main theories of hippocampal function-cognitive map theory and index theory-which, when carefully analyzed, make exactly the same predictions about hippocampal topography. Such abstract topographical map would be extremely hard to find using the methods commonly employed in the literature, but there are some approaches that may, in the future, make possible to characterize the topographical organization in the hippocampus and other high-order brain regions.