Circuit compensation is often observed in patients with acute ischemic stroke, suggesting the importance of the interaction between brain regions. Also, contextual fear memory is an association between multisensory contexts and fearful stimuli, for which the interaction between the hippocampus and the amygdala is believed to be critical. To understand how focal ischemia in one region could influence the other region, we used a modified photo-thrombosis to induce focal ischemia in the hippocampus or the amygdala or both in freely-moving rats. We found that the learning curve and short-term memory (STM) were not affected in the rats although focal ischemia was induced 5 h before learning in either the hippocampus or the amygdala; these were impaired by the induction of ischemia in both the regions. Furthermore, the learning curve and STM were impaired when ischemia was induced 24 h before learning in either the hippocampus or the amygdala when the synaptic transmission was altered in one region because of is...

Psychosis disorder is a debilitating disorder characterized by multiple admissions to psychiatric care facilities, higher unemployment rates, and decreased life expectancy. All of which create a high burden on the patient, their family, and the healthcare system. Understanding the basic mechanisms of psychotic disorder is essential for early discovery and facilitating better care for those suffering from it (Correll et al., 2018). The dopamine hypothesis of schizophrenia (Howes et al., 2009) suggests that dysregulation in dopamine signaling is the main cause of psychosis. Consistent with this theory, the ventral-tegmental area (VTA) is a pivoting region in psychosis in both animals and humans (Modinos et al., 2015). Individuals suffering from psychosis have elevated dopaminergic activity in the VTA. Such dysregulations were also found in prodromal syndromes (before full-blown development of psychosis; Howes et al., 2009), suggesting a causal effect of …

The recent trend toward an industrialization of brain exploration and the technological prowess of artificial intelligence algorithms and high-performance computing has caught the imagination of the public. These impressive advances are fueling an uncontrolled societal hype, the more amplified, the more “Blue Sky” the claim is. Will we ever be able to simulate a brain in silico ? Will “it” (the digital avatar) be conscious? The Blue Brain Project (BBP) and the European flagship the Human Brain Project (HBP) have surfed on this wave for the past 10 years. Their already significant lifetimes now offer new case studies for neuroscience sociology and epistemology, as the projects mature. Their distinctive “Blue Sky” flavor has been a key feature in securing unprecedented funding (more than one billion Euros) mostly through supranational institutions. The longitudinal analysis of these ventures provides clues to how the neuromyth they propagate sells science, in a scientific world based on an economy of promises.

About one year ago, I learnt of the existence of In Silico . It did not come as a surprise, as I had expected that toward the end of the Human Brain Project (HBP)’s 10-year funding period, there will be a rush of articles and generally increased media interest in covering the project’s progress, achievements, and failures, although In Silico is special, given its 10-year time frame. I joined the HBP in 2014 and lead today one of three science work packages. For this documentary, I expected to hear requests for interviews, but there was literally nothing of that sort. After I have finally watched In Silico , I understand why. The documentary is in fact not about HBP, despite claims to the contrary by a previous review (Abbott, 2020). In Silico director, Noah Hutton, rather focuses on his fascination with Henry Markram’s 10-year vision of building a brain from the bottom up, the Blue Brain Project (BBP). As will be described towards the end, the HBP follows a stringent and much broader concept of integrating...

How can we evaluate the positive impact that visionary people can have on science? Should we support funneling large amounts of money to big projects? Both questions arose when I watched Noah Hutton’s film, In Silico .* I invited several prominent scientists to comment on the film’s main topic, modeling the human brain, in a special collection for eNeuro . The film tells the 10-year journey beginning with Henry Markram’s 2009 TED talk (https://www.ted.com/talks/henry\_markram\_a\_brain\_in\_a\_supercomputer), where he announced that the brain could be modeled within 10 years in a supercomputer. The scientific initiative began in 2005 at École Polytechnique Fédérale de Lausanne when Markram founded and directed the first scientific initiative toward his goal: the Blue Brain Project (https://www.epfl.ch/research/domains/bluebrain/). Then, in 2012, the European Union selected the Human Brain Project (https://www.humanbrainproject.eu/en/), also then led by Markram, as one of two flagship programs to be awarde...

Persistent firing is believed to be a cellular correlate of working memory. While the effects of noradrenaline (NA) on working memory have widely been described, its effect on the cellular mechanisms of persistent firing remains largely unknown. Using in vitro intracellular recordings, we demonstrate that persistent firing is supported by individual neurons in hippocampal CA1 pyramidal cells through cholinergic receptor activation, but is dramatically attenuated by NA. In contrast to the classical theory that recurrent synaptic excitation supports persistent firing, suppression of persistent firing by NA was independent of synaptic transmission, indicating that the mechanism is intrinsic to individual cells. In agreement with detrimental effects of cyclic adenosine monophosphate (cAMP) on working memory, we demonstrate that the suppressive effect of NA was through cAMP-PKA pathway. In addition, activation of β1 and/or β3 adrenergic receptors, which increases cAMP levels, suppressed persistent firing. These...

Locomotion, scratching, and stabilization of the body orientation in space are basic motor functions which are critically important for animal survival. Their execution requires coordinated activity of muscles located in the left and right halves of the body. Commissural interneurons (CINs) are critical elements of the neuronal networks underlying the left-right motor coordination. V0 interneurons (characterized by the early expression of the transcription factor Dbx1) contain a major class of CINs in the spinal cord (excitatory V0V, and inhibitory V0D), and a small subpopulation of excitatory ipsilaterally projecting interneurons. The role of V0 CINs in left-right coordination during forward locomotion was demonstrated earlier. Here, to reveal the role of glutamatergic V0 and other V0 subpopulations in control of backward locomotion, scratching, righting behavior, and postural corrections, kinematics of these movements performed by wild-type mice and knockout mice with glutamatergic V0 or all V0 interneur...

The distinctiveness of neural information representation is crucial for successful memory performance but declines with advancing age. Computational models implicate age-related neural dedifferentiation on the level of item representations, but previous studies mostly focused on age differences of categorical information representation in higher-order visual regions. In an age-comparative fMRI study, we combined univariate analyses and whole-brain searchlight pattern similarity analyses to elucidate age differences in neural distinctiveness at both category and item levels and their relation to memory. Thirty-five younger (18–27 years old) and 32 older (67–75 years old) women and men incidentally encoded images of faces and houses, followed by an old/new recognition memory task. During encoding, age-related neural dedifferentiation was shown as reduced category-selective processing in ventral visual cortex and impoverished item specificity in occipital regions. Importantly, successful subsequent memory per...

The addition of new neurons to existing neural circuits in the adult brain remains of great interest to neurobiology because of its therapeutic implications. The premier model for studying this process has been the hippocampal dentate gyrus in mice, where new neurons are added to mature circuits during adulthood. Notably, external factors such as an enriched environment (EE) and exercise markedly increase hippocampal neurogenesis. Here, we demonstrate that EE acts by increasing fibroblast growth factor receptor (FGFR) function autonomously within neurogenic cells to expand their numbers in adult male and female mice. FGFRs activated by EE signal through their mediators, FGFR substrate (FRS), to induce stem cell proliferation, and through FRS and phospholipase Cγ to increase the number of adult-born neurons, providing a mechanism for how EE promotes adult neurogenesis. SIGNIFICANCE STATEMENT How the environment we live in affects cognition remains poorly understood. In the current study, we explore the m...

Trauma can cause dysfunctional fear regulation leading some people to develop disorders such as post-traumatic stress disorder (PTSD). The amygdala regulates fear, whereas PACAP (pituitary adenylate activating peptide) and PAC1 receptors are linked to PTSD symptom severity at genetic/epigenetic levels, with a strong link in females with PTSD. We discovered a PACAPergic projection from the basomedial amygdala (BMA) to the medial intercalated cells (mICCs) in adult mice. In vivo optogenetic stimulation of this pathway increased cfos expression in mICCs, decreased fear recall and increased fear extinction. Selective deletion of PAC1 receptors from the mICCs in females reduced fear acquisition, but enhanced fear generalization and reduced fear extinction in males. Optogenetic stimulation of the BMA-mICCs PACAPergic pathway produced excitatory postsynaptic currents (EPSCs) in mICC neurons, which were enhanced by the PAC1 receptor antagonist, PACAP 6-38. Our findings show that mICCs modulate contextual fear in a...