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Category: neuroscience – Page 610

Hippocampal Egr1-Dependent Neuronal Ensembles Negatively Regulate Motor Learning

Motor skills learning is classically associated with brain regions including cerebral and cerebellar cortices and basal ganglia nuclei. Less is known about the role of the hippocampus in the acquisition and storage of motor skills. Here, we show that mice receiving a long-term training in the accelerating rotarod display marked hippocampal transcriptional changes and reduced pyramidal neurons activity in the CA1 region when compared with naive mice. Then, we use mice in which neural ensembles are permanently labeled in an Egr1 activity-dependent fashion. Using these mice, we identify a subpopulation of Egr1-expressing pyramidal neurons in CA1 activated in short-term (STT) and long-term (LTT) trained mice in the rotarod task. When Egr1 is downregulated in the CA1 or these neuronal ensembles are depleted, motor learning is improved whereas their chemogenetic stimulation impairs motor learning performance. Thus, Egr1 organizes specific CA1 neuronal ensembles during the accelerating rotarod task that limit motor learning. These evidences highlight the role of the hippocampus in the control of this type of learning and we provide a possible underlying mechanism.

SIGNIFICANCE STATEMENT It is a major topic in neurosciences the deciphering of the specific circuits underlying memory systems during the encoding of new information. However, the potential role of the hippocampus in the control of motor learning and the underlying mechanisms has been poorly addressed. In the present work we show how the hippocampus responds to motor learning and how the Egr1 molecule is one of the major responsible for such phenomenon controlling the rate of motor coordination performances.

Electrocorticographic evidence of a common neurocognitive sequence for mentalizing about the self and others

Using electrocorticography (ECoG), we probed the neurocognitive substrates of mentalizing at the level of neuronal populations. We found that mentalizing about the self and others recruited near-identical cortical sites (Fig. 5a, b) in a common spatiotemporal sequence (Figs. 5 c and 6). Within our ROIs, activations began in visual cortex, followed by temporoparietal DMN regions (TPJ, ATL, and PMC), and lastly in mPFC regions (amPFC, dmPFC, and vmPFC; Fig. 3e, f). Critically, regions with later activations exhibited greater functional specialization for mentalizing as measured by three metrics: functional specificity for mentalizing versus arithmetic (Figs. 3 c, d and 4b), self/other differentiation in activation timing (Fig. 5c, d), and temporal associations with behavioral responses (Fig. 4D and Table 1). Taken together, these results reveal a common neurocognitive sequence28,29,30,31 for self-and other-mentalizing, beginning in visual cortex (low specialization), ascending through temporoparietal DMN areas (intermediate specialization), then reaching its apex in mPFC regions (high specialization).

Our results are consistent with gradient-based models of brain function, which posit that concrete sensorimotor processing in unimodal regions (e.g., visual cortex) gradually yields to increasingly abstract and inferential processing in ‘high-level’ transmodal regions like mPFC41,42. We found that the strength of self/other differences in activation timing increased along a gradient from visual cortex to mPFC. Specifically, other-mentalizing evoked slower (Fig. 5c) and lengthier (Fig. 5d) activations than self-mentalizing throughout successive DMN ROIs. These self/other functional differences corresponded with self/other differences in RTBehav (Supplementary Fig. 4), although the two were often dissociable (Table 1). Thus, perhaps because we know ourselves better than others, other-mentalizing may require lengthier processing at more abstract and inferential levels of representation, ultimately resulting in slower behavioral responses.

What might our results imply about extant fMRI findings? Hundreds of fMRI studies consistently suggest that: TPJ and dmPFC are most crucial for mentalizing6,8,11,12,43,44,45,46, and dmPFC is selective for thinking about others over oneself 32,33,34,35. However, when examined with ECoG, we found that both pieces of received wisdom are not what they seem. Below, we discuss both issues before moving onto our peculiar vmPFC results, and then conclude with systems-level discussion.

Neurological and psychiatric risk trajectories after SARS-CoV-2 infection: an analysis of 2-year retrospective cohort studies including 1 284 437 patients

This analysis of 2-year retrospective cohort studies of individuals diagnosed with COVID-19 showed that the increased incidence of mood and anxiety disorders was transient, with no overall excess of these diagnoses compared with other respiratory infections. In contrast, the increased risk of psychotic disorder, cognitive deficit, dementia, and epilepsy or seizures persisted throughout. The differing trajectories suggest a different pathogenesis for these outcomes. Children have a more benign overall profile of psychiatric risk than do adults and older adults, but their sustained higher risk of some diagnoses is of concern. The fact that neurological and psychiatric outcomes were similar during the delta and omicron waves indicates that the burden on the health-care system might continue even with variants that are less severe in other respects. Our findings are relevant to understanding individual-level and population-level risks of neurological and psychiatric disorders after SARS-CoV-2 infection and can help inform our responses to them.

National institute for health and care research oxford health biomedical research centre, the wolfson foundation, and MQ mental health research.

Exposure to phenytoin associates with a lower risk of post-COVID cognitive deficits: a cohort study

A proportion of patients experience long-lasting symptoms in the weeks and months after a diagnosis of COVID-19. 1–3 Of those symptoms, cognitive impairment (also referred to as ‘brain fog’) is particularly worrisome: it is one of the most common, 4, 5 can affect those with even relatively mild acute COVID-19 illness 1, 5 and results in the inability to work for many affected patients. 3 While emerging research is starting to characterize the clinical presentation of post-COVID cognitive deficits, 6 its pathogenesis remains elusive. Identifying therapeutic targets is critical to reducing the burden of this COVID-19 complication.

Endotheliopathy has been hypothesized as one potential mechanism underlying post-COVID cognitive deficits. 7 According to recent research, microvascular brain pathology following COVID-19 can be caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease Mpro cleaving nuclear factor-κB essential modulator thus inducing the death of brain endothelial cells. 8 The same study showed that pharmacologically inhibiting receptor-interacting protein kinase (RIPK) signaling prevents the Mpro-induced microvascular pathology. 8

This research leads to the following hypothesis: exposure to a pharmacological inhibitor of RIPK signaling at the time of COVID-19 infection reduces the risk of post-COVID cognitive deficits. In this study, we tested this hypothesis using a retrospective cohort study based on electronic health records (EHRs) data. While many pharmacological agents inhibit RIPK signaling, 9 most are only used in very rare clinical scenarios (e.g. sunitinib for the treatment of advanced renal cell carcinoma or pancreatic neuroendocrine tumors). The exception is phenytoin which is used as an anti-epileptic drug and which, among its other effects, is a RIPK1 inhibitor protecting against necroptosis. 10, 11 In this study, we compared the incidence of post-COVID cognitive deficits between patients exposed to phenytoin and matched cohorts of patients exposed to other anti-epileptic drugs at the time of their COVID-19 diagnosis.

Neuralink will probably not be wanted

Meta CEO Mark Zuckerberg was a recent guest on The Joe Rogan Experience podcast, and during the episode, he discussed, among other things, neural technology. During his conversation, Zuckerberg remarked that Elon Musk’s Neuralink would probably not be popular in the next 10–15 years because “normal people” would not want to have devices implanted in their brains that are made of non-mature technology.

Zuckerberg admitted that Meta is researching neural interface tech as part of the company’s push into the metaverse, though he also noted that the tech company is focusing on innovations that can receive signals from the brain but does not send any information back to it.

In later comments, the Meta CEO noted that companies like Elon Musk’s Neuralink, which is developing a device that can be implanted into people’s skulls, is taking neural technology “super far-off.” Neuralink’s implant is designed to record and stimulate brain activity, which Musk has stated could help people address conditions such as obesity.

Synthetic embryo grown without sperm, womb. It has a brain and a beating heart

In a new medical breakthrough, scientists have successfully grown a synthetic embryo of a mouse without male sperm and a female womb. They used stem cells from mice to recreate the first stage of life and successfully developed an embryo with a brain, beating heart, and vitals for other organs.

The natural process of life was mimicked in the lab without eggs or sperm but with the body’s master cells, which can develop into almost any cell type in the body. The embryo was developed 8 ½ days after fertilization, containing the same structures as a natural one.

The study published in the journal Nature states that their result demonstrates the self-organization ability of embryonic and two types of extra-embryonic stem cells to reconstitute mammalian development. The researchers induced expression of a particular set of genes and established a unique environment for their interactions and got the stem cells to ‘talk’ to each other.

Mark Zuckerberg thinks ‘normal people’ won’t want Neuralink chips in their brains soon, but sees a future where people text their loved ones

Meta CEO Mark Zuckerberg outlined the company’s approach to neural interface technology — tech which lets you control technology with your mind — in an interview on podcast The Joe Rogan Experience.

Zuckerberg said Meta is researching neural interface tech as part of its push into the metaverse.

He said the company is primarily focused on tech which can receive signals from the brain but does send any information back to it.