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In the immune system, Major Histocompatibility Complex class Ⅰ (MHC-I) molecules are located on the surface of most nucleated cells in vertebrates where they mediate immune responses. Accumulating evidence indicates that MHC-I molecules are also expressed in the central nervous system (CNS) where they play important roles that are significantly different from their immune functions. Classical MHC-I molecules are temporally and spatially expressed in the developing and adult CNS, where they participate in synaptic formation, remodeling and plasticity. Therefore, clarifying the regulation of MHC-I expression is necessary to develop an accurate understanding of its function in the CNS. Here, we show that microRNA 34a (miR34a), a brain enriched noncoding RNA, is temporally expressed in developing hippocampal neurons, and its expression is significantly increased after MHC-I protein abundance is decreased in the hippocampus. Computational algorithms identify putative miR34a target sites in the 3’UTR of MHC-I mRNA, and here we demonstrate direct targeting of miR34a to MHC-I mRNA using a dual luciferase reporter assay system. MiR34a targeting can decrease constitutive MHC-I expression in both Neuro-2a neuroblastoma cells and primary hippocampal neurons. Finally, miR34a mediated reduction of MHC-I results in increased dendritic growth and branching in cultured hippocampal neurons. Taken together, our findings identify miR34a as a novel regulator of MHC-I for shaping neural morphology in developing hippocampal neurons.

Neuroscience findings emphasize the role of dendritic branching in neocortical pyramidal neurons for non-linear computations and signal processing. Dendritic branches facilitate temporal feature detection via synaptic delays that enable coincidence detection (CD) mechanisms. Spiking neural networks highlight the significance of delays for spatio-temporal pattern recognition in feed-forward networks, eliminating the need for recurrent structures. Here, we introduce DenRAM, a novel analog electronic feed-forward spiking neural network with dendritic compartments. Utilizing 130 nm technology integrated with resistive RAM (RRAM), DenRAM incorporates both delays and synaptic weights. By configuring RRAMs to emulate bio-realistic delays and exploiting their heterogeneity, DenRAM mimics synaptic delays and efficiently performs CD for pattern recognition. Hardware-aware simulations on temporal benchmarks show DenRAM’s robustness against hardware noise, and its higher accuracy over recurrent networks. DenRAM advances temporal processing in neuromorphic computing, optimizes memory usage, and marks progress in low-power, real-time signal processing The authors present DenRAM, a hardware realization of spiking neural network with dendritic architecture. It utilizes memristive devices to implement both delay and weight parameters, enhancing low-power signal processing with reduced memory use.

Understanding the brain requires understanding neurons’ functional responses to the circuit architecture shaping them. Here we introduce the MICrONS functional connectomics dataset with dense calcium imaging of around 75,000 neurons in primary visual cortex (VISp) and higher visual areas (VISrl, VISal and VISlm) in an awake mouse that is viewing natural and synthetic stimuli. These data are co-registered with an electron microscopy reconstruction containing more than 200,000 cells and 0.5 billion synapses. Proofreading of a subset of neurons yielded reconstructions that include complete dendritic trees as well the local and inter-areal axonal projections that map up to thousands of cell-to-cell connections per neuron. Released as an open-access resource, this dataset includes the tools for data retrieval and analysis 1 , 2 . Accompanying studies describe its use for comprehensive characterization of cell types 3 , 4 , 5 – 6 , a synaptic level connectivity diagram of a cortical column 4 , and uncovering cell-type-specific inhibitory connectivity that can be linked to gene expression data 4 , 7 . Functionally, we identify new computational principles of how information is integrated across visual space 8 , characterize novel types of neuronal invariances 9 and bring structure and function together to uncover a general principle for connectivity between excitatory neurons within and across areas 10 , 11 . Dense calcium imaging combined with co-registered high-resolution electron microscopy reconstruction of the brain of the same mouse provide a functional connectomics map of tens of thousands of neurons of a region of the primary cortex and higher visual areas.

Sex hormones have been implicated in neurite outgrowth, synaptogenesis, dendritic branching, myelination and other important mechanisms of neural plasticity. Here we review the evidence from animal experiments and human studies reporting interactions between sex hormones and the dominant neurotransmitters, such as serotonin, dopamine, GABA and glutamate. We provide an overview of accumulating data during physiological and pathological conditions and discuss currently conceptualized theories on how sex hormones potentially trigger neuroplasticity changes through these four neurochemical systems. Many brain regions have been demonstrated to express high densities for estrogen- and progesterone receptors, such as the amygdala, the hypothalamus, and the hippocampus. As the hippocampus is of particular relevance in the context of mediating structural plasticity in the adult brain, we put particular emphasis on what evidence could be gathered thus far that links differences in behavior, neurochemical patterns and hippocampal structure to a changing hormonal environment. Finally, we discuss how physiologically occurring hormonal transition periods in humans can be used to model how changes in sex hormones influence functional connectivity, neurotransmission and brain structure in vivo.

The active properties of dendrites can support local nonlinear operations, but previous imaging and electrophysiological measurements have produced conflicting views regarding the prevalence and selectivity of local nonlinearities in vivo. We imaged calcium signals in pyramidal cell dendrites in the motor cortex of mice performing a tactile decision task. A custom microscope allowed us to image the soma and up to 300 μm of contiguous dendrite at 15 Hz, while resolving individual spines. New analysis methods were used to estimate the frequency and spatial scales of activity in dendritic branches and spines. The majority of dendritic calcium transients were coincident with global events. However, task-associated calcium signals in dendrites and spines were compartmentalized by dendritic branching and clustered within branches over approximately 10 μm. Diverse behavior-related signals were intermingled and distributed throughout the dendritic arbor, potentially supporting a large learning capacity in individual neurons.

Aging drives a progressive decline in cognition and decreases synapse numbers and synaptic function in the brain, thereby increasing the risk for neurodegenerative disease. Pioneering studies showed that introduction of blood from young mice into aged mice reversed age-associated cognitive impairments and increased synaptic connectivity in brain, suggesting that young blood contains specific factors that remediate age-associated decreases in brain function. However, whether such factors in blood from young animals act directly on neurons to enhance synaptic connectivity, or whether they act by an indirect mechanism remains unknown. Moreover, which factors in young blood mediate cognitive improvements in old mice is incompletely understood. Here, we show that serum extracted from the blood of young but not old mice, when applied to neurons trans-differentiated from human embryonic stem cells, directly increased dendritic arborization, augmented synapse numbers, doubled dendritic spine-like structures, and elevated synaptic N-methyl-D-aspartate (NMDA) receptors, thereby increasing synaptic connectivity. Mass spectrometry revealed that thrombospondin-4 (THBS4) and SPARC-like protein 1 (SPARCL1) were enriched in serum from young mice. Strikingly, recombinant THBS4 and SPARCL1 both increased dendritic arborization and doubled synapse numbers in cultured neurons. In addition, SPARCL1 but not THBS4 tripled NMDA receptor-mediated synaptic responses. Thus, at least two proteins enriched in young blood, THBS4 and SPARCL1, directly act on neurons as synaptogenic factors. These proteins may represent rejuvenation factors that enhance synaptic connectivity by increasing dendritic arborization, synapse formation, and synaptic transmission.

Lithium dendrite growth in inorganic solid-state electrolytes acts as a main stumbling block for the commercial development of all-solid-state lithium batteries. Indeed, Li dendrites often lead to solid-state electrolyte fractures, undermining device integrity and safety. Despite the significance of these issues, the mechanisms driving the solid-state electrolyte fracture process at the microscopic level remain poorly understood. Here, via operando optical and ex situ dark field X-ray microscopy measurements of LiSn∣single-crystal Li 6.5 La 3 Zr 1.5 Ta 0.5 O 12 ∣LiSn symmetric cells, we provide insights into solid-state electrolyte strain patterns and lattice orientation changes associated with dendrite growth. We report the observation of dislocations in the immediate vicinity of dendrite tips, including one instance where a dislocation is anchored directly to a tip. This latter occurrence in single-crystalline ceramics suggests an interplay between dendrite proliferation and dislocation formation. We speculate that the mechanical stress induced by dendrite expansion triggers dislocation generation. These dislocations seem to influence the fracture process, potentially affecting the directional growth and branching observed in lithium dendrites. Lithium dendrite growth in solid-state electrolytes is a significant challenge for next-generation battery development. Here, authors used dark-field X-ray microscopy to investigate dislocations near dendrite tips, suggesting that stress-induced dislocation may influence dendrite branching and material fracture.

The loss of nigrostriatal dopamine neurons in Parkinson’s disease induces a reduction in the number of dendritic spines on medium spiny neurons (MSNs) of the striatum expressing D 1 or D 2 dopamine receptor. Consequences on MSNs expressing both receptors (D 1 /D 2 MSNs) are currently unknown. We looked for changes induced by dopamine denervation in the density, regional distribution and morphological features of D 1 /D 2 MSNs, by comparing 6-OHDA-lesioned double BAC transgenic mice ( Drd1a -tdTomato/ Drd2 -EGFP) to sham-lesioned animals. D 1 /D 2 MSNs are uniformly distributed throughout the dorsal striatum (1.9% of MSNs). In contrast, they are heterogeneously distributed and more numerous in the ventral striatum (14.6% in the shell and 7.3% in the core). Compared to D 1 and D 2 MSNs, D 1 /D 2 MSNs are endowed with a smaller cell body and a less profusely arborized dendritic tree with less dendritic spines. The dendritic spine density of D 1 /D 2 MSNs, but also of D 1 and D 2 MSNs, is significantly reduced in 6-OHDA-lesioned mice. In contrast to D 1 and D 2 MSNs, the extent of dendritic arborization of D 1 /D 2 MSNs appears unaltered in 6-OHDA-lesioned mice. Our data indicate that D 1 /D 2 MSNs in the mouse striatum form a distinct neuronal population that is affected differently by dopamine deafferentation that characterizes Parkinson’s disease.

During embryonic development and adulthood, Reelin exerts several important functions in the brain including the regulation of neuronal migration, dendritic growth and branching, dendritic spine formation, synaptogenesis and synaptic plasticity. As a consequence, the Reelin signaling pathway has been associated with several human brain disorders such as lissencephaly, autism, schizophrenia, bipolar disorder, depression, mental retardation, Alzheimer’s disease and epilepsy. Several elements of the signaling pathway are known. Core components, such as the Reelin receptors very low-density lipoprotein receptor (VLDLR) and Apolipoprotein E receptor 2 (ApoER2), Src family kinases Src and Fyn, and the intracellular adaptor Disabled-1 (Dab1), are common to most but not all Reelin functions. Other downstream effectors are, on the other hand, more specific to defined tasks. Reelin is a large extracellular protein, and some aspects of the signal are regulated by its processing into smaller fragments. Rather than being inhibitory, the processing at two major sites seems to be fulfilling important physiological functions. In this review, I describe the various cellular events regulated by Reelin and attempt to explain the current knowledge on the mechanisms of action. After discussing the shared and distinct elements of the Reelin signaling pathway involved in neuronal migration, dendritic growth, spine development and synaptic plasticity, I briefly outline the data revealing the importance of Reelin in human brain disorders.

Autism Spectrum Disorders (ASD) comprise a range of early age-onset neurodevelopment disorders with genetic heterogeneity. Most ASD related genes are involved in synaptic function, which is regulated by mature brain-derived neurotrophic factor (mBDNF) and its precursor proBDNF in a diametrically opposite manner: proBDNF inhibits while mBDNF potentiates synapses. Here we generated a knock-in mouse line (BDNF met/leu ) in which the conversion of proBDNF to mBDNF is attenuated. Biochemical experiments revealed residual mBDNF but excessive proBDNF in the brain. Similar to other ASD mouse models, the BDNF met/leu mice showed reduced dendritic arborization, altered spines, and impaired synaptic transmission and plasticity in the hippocampus. They also exhibited ASD-like phenotypes, including stereotypical behaviors and deficits in social interaction. Moreover, the plasma proBDNF/mBDNF ratio was significantly increased in ASD patients compared to normal children in a case-control study. Thus, deficits in proBDNF to mBDNF conversion in the brain may contribute to ASD-like behaviors, and plasma proBDNF/mBDNF ratio may be a potential biomarker for ASD.