Lucian Williams, Jessica Larsen
Neurological disorders pose a significant burden on individuals and society, affecting millions worldwide. These disorders, including but not limited to Alzheimer's disease, Parkinson's disease, and Huntington's disease, often have limited treatment options and can lead to progressive degeneration and disability. Gene editing technologies offer a promising avenue for potential cures by targeting and correcting the underlying genetic mutations responsible for neurologic disorders. However, efficient delivery methods are crucial for the successful application of gene editing technologies in the context of neurological disorders...
November 30, 2023: Progress in Neurobiology
Yordanka Zafirova, Anna Bognár, Rufin Vogels
Traditionally, the neural processing of faces and bodies is studied separately, although they are encountered together, as parts of an agent. Despite its social importance, it is poorly understood how faces and bodies interact, particularly at the single-neuron level. Here, we examined the interaction between faces and bodies in the macaque inferior temporal (IT) cortex, targeting an fMRI-defined patch. We recorded responses of neurons to monkey images in which the face was in its natural location (natural face-body configuration), or in which the face was mislocated with respect to the upper body (unnatural face-body configuration)...
November 30, 2023: Progress in Neurobiology
Francesco Bove, Benedetta Angeloni, Pasquale Sanginario, Paolo Maria Rossini, Paolo Calabresi, Riccardo Di Iorio
Levodopa-induced dyskinesias (LIDs) are a common complication in patients with Parkinson's disease (PD). A complex cascade of electrophysiological and molecular events that induce aberrant plasticity in the cortico-basal ganglia system plays a key role in the pathophysiology of LIDs. In the striatum, multiple neurotransmitters regulate the different forms of physiological synaptic plasticity to provide it in a bidirectional and Hebbian manner. In PD, impairment of both long-term potentiation (LTP) and long-term depression (LTD) progresses with disease and dopaminergic denervation of striatum...
November 29, 2023: Progress in Neurobiology
Konrad R Dabrowski, Gabriele Floris, Aria Gillespie, Stephanie E Sillivan
The orbitofrontal cortex (OFC) is a vital component of brain reward circuitry that is important for reward seeking behavior. However, OFC-mediated molecular mechanisms underlying rewarding behavior are understudied. Here, we report the first circular RNA (circRNA) profile associated with appetitive reward and identify regulation of 92 OFC circRNAs by sucrose self-administration. Among these changes, we observed downregulation of circNrxn3, a circRNA originating from neurexin 3 (Nrxn3), a gene involved in synaptogenesis, learning, and memory...
November 28, 2023: Progress in Neurobiology
Deepak Prasad Gupta, Anup Bhusal, Md Habibur Rahman, Jae-Hong Kim, Youngshik Choe, Jaemyung Jang, Hyun Jin Jung, Un-Kyung Kim, Jin-Sung Park, Lee-So Maeng, Kyoungho Suk, Gyun Jee Song
Peripheral nerve injury disrupts the Schwann cell-axon interaction and the cellular communication between them. The peripheral nervous system has immense potential for regeneration extensively due to the innate plastic potential of Schwann cells (SCs) that allows SCs to interact with the injured axons and exert specific repair functions essential for peripheral nerve regeneration. In this study, we show that EBP50 is essential for the repair function of SCs and regeneration following nerve injury. The increased expression of EBP50 in the injured sciatic nerve of control mice suggested a significant role in regeneration...
November 6, 2023: Progress in Neurobiology
Sojeong Pak, Minseok Lee, Sangwon Lee, Huilin Zhao, Eunha Baeg, Sunggu Yang, Sungchil Yang
Tinnitus induced by hearing loss is caused primarily by irreversible damage to the peripheral auditory system, which results in abnormal neural responses and frequency map disruption in the central auditory system. It remains unclear whether and how electrical rehabilitation of the auditory cortex can alleviate tinnitus. We hypothesize that stimulation of the cortical surface can alleviate tinnitus by enhancing neural responses and promoting frequency map reorganization. To test this hypothesis, we assessed and activated cortical maps using our newly designed graphene-based electrode array with a noise-induced tinnitus animal model...
November 2, 2023: Progress in Neurobiology
Jan A Knobloch, Gilles Laurent, Marcel A Lauterbach
Dendritic spines are key structures for neural communication, learning and memory. Spine size and shape probably reflect synaptic strength and learning. Imaging with superresolution STED microscopy the detailed shape of the majority of the spines of individual neurons in turtle cortex (Trachemys scripta elegans) revealed several distinguishable shape classes. Dendritic spines of a given class were not distributed randomly, but rather decorated significantly more often some dendrites than others. The individuality of dendrites was corroborated by significant inter-dendrite differences in other parameters such as spine density and length...
October 26, 2023: Progress in Neurobiology
Daniel Ramírez de Mingo, Paula López-García, María Eugenia Vaquero, Rubén Hervás, Douglas V Laurents, Mariano Carrión-Vázquez
How functional amyloids are regulated to restrict their activity is poorly understood. The cytoplasmic polyadenylation element-binding protein 3 (CPEB3) is an RNA-binding protein that adopts an amyloid state key for memory persistence. Its monomer represses the translation of synaptic target mRNAs while phase separated, whereas its aggregated state acts as a translational activator. Here, we have explored the sequence-driven molecular determinants behind the functional aggregation of human CPEB3 (hCPEB3). We found that the intrinsically disordered region (IDR) of hCPEB3 encodes both an amyloidogenic and a phase separation domain, separated by a poly-A-rich region...
October 26, 2023: Progress in Neurobiology
Archana Proddutur, Susan Nguyen, Chia-Wei Yeh, Akshay Gupta, Vijayalakshmi Santhakumar
Axo-axonic cells (AACs) provide specialized inhibition to the axon initial segment (AIS) of excitatory neurons and can regulate network output and synchrony. Although hippocampal dentate AACs are structurally altered in epilepsy, physiological analyses of dentate AACs are lacking. We demonstrate that parvalbumin neurons in the dentate molecular layer express PTHLH, an AAC marker, and exhibit morphology characteristic of AACs. Dentate AACs show high-frequency, non-adapting firing but lack persistent firing in the absence of input and have higher rheobase than basket cells suggesting that AACs can respond reliably to network activity...
October 26, 2023: Progress in Neurobiology
Yuri Zilberter, Dennis R Tabuena, Misha Zilberter
Neurodegenerative diseases (NDDs) causing cognitive impairment and dementia are difficult to treat due to the lack of understanding of primary initiating factors. Meanwhile, major sporadic NDDs share many risk factors and exhibit similar pathologies in their early stages, indicating the existence of common initiation pathways. Glucose hypometabolism associated with oxidative stress is one such primary, early and shared pathology, and a likely major cause of detrimental disease-associated cascades; targeting this common pathology may therefore be an effective preventative strategy for most sporadic NDDs...
October 12, 2023: Progress in Neurobiology
R J Bufacchi, A Battaglia-Mayer, G D Iannetti, R Caminiti
Classical neurophysiology suggests that the motor cortex (MI) has a unique role in action control. In contrast, this review presents evidence for multiple parieto-frontal spinal command modules that can bypass MI. Five observations support this modular perspective: (i) the statistics of cortical connectivity demonstrate functionally-related clusters of cortical areas, defining functional modules in the premotor, cingulate, and parietal cortices; (ii) different corticospinal pathways originate from the above areas, each with a distinct range of conduction velocities; (iii) the activation time of each module varies depending on the task, and different modules can be activated simultaneously; (iv) a modular architecture with direct motor output is faster and less metabolically expensive than an architecture that relies on MI, given the slow connections between MI and other cortical areas; (v) lesions of the areas composing parieto-frontal modules have different effects from lesions of MI...
October 11, 2023: Progress in Neurobiology
Alex I Wiesman, Jason da Silva Castanheira, Clotilde Degroot, Edward A Fon, Sylvain Baillet, Prevent-Ad Research Group, Quebec Parkinson Network
Patients with Parkinson's disease (PD) exhibit multifaceted changes in neurophysiological brain activity, hypothesized to represent a global cortical slowing effect. Using task-free magnetoencephalography and extensive clinical assessments, we found that neurophysiological slowing in PD is differentially associated with motor and non-motor symptoms along a sagittal gradient over the cortical anatomy. In superior parietal regions, neurophysiological slowingFfig reflects an adverse effect and scales with cognitive and motor impairments, while across the inferior frontal cortex, neurophysiological slowing is compatible with a compensatory role...
October 11, 2023: Progress in Neurobiology
Daniel de Castro Medeiros, Carina Plewnia, Renan Viana Mendes, Clarissa Anna Pisanò, Laura Boi, Marcio Flávio Dutra Moraes, Cleiton Lopes Aguiar, Gilberto Fisone
Excessive daytime sleepiness (EDS) and sleep fragmentation are often observed in Parkinson's disease (PD) patients and are poorly understood despite their considerable impact on quality of life. We examined the ability of a neurotoxin-based mouse model of PD to reproduce these disorders and tested the potential counteracting effects of dopamine replacement therapy. Experiments were conducted in female mice with a unilateral 6-hydroxydopamine lesion of the medial forebrain bundle, leading to the loss of dopamine neurons projecting to the dorsal and ventral striatum...
October 5, 2023: Progress in Neurobiology
Wenying Liu, Yan Li, Tan Zhao, Min Gong, Xuechu Wang, Yue Zhang, Lingzhi Xu, Wenwen Li, Yan Li, Jianping Jia
N-Methyl-D-aspartate glutamate receptors (NMDARs) are involved in multiple physiopathological processes, including synaptic plasticity, neuronal network activities, excitotoxic events, and cognitive impairment. Abnormalities in NMDARs can initiate a cascade of pathological events, notably in Alzheimer's disease (AD) and even other neuropsychiatric disorders. The subunit composition of NMDARs is plastic, giving rise to a diverse array of receptor subtypes. While they are primarily found in neurons, NMDAR complexes, comprising both traditional and atypical subunits, are also present in non-neuronal cells, influencing the functions of various peripheral tissues...
September 30, 2023: Progress in Neurobiology
Anastasia Brodovskaya, Huayu Sun, Nadia Adotevi, Ian C Wenker, Keri E Mitchell, Rachel T Clements, Jaideep Kapur
Repeated generalized tonic-clonic seizures (GTCSs) are the most critical risk factor for sudden unexpected death in epilepsy (SUDEP). GTCSs can cause fatal apnea. We investigated neuronal plasticity mechanisms that precipitate postictal apnea and seizure-induced death. Repeated seizures worsened behavior, precipitated apnea, and enlarged active neuronal circuits, recruiting more neurons in such brainstem nuclei as periaqueductal gray (PAG) and dorsal raphe, indicative of brainstem plasticity. Seizure-activated neurons are more excitable and have enhanced AMPA-mediated excitatory transmission after a seizure...
September 29, 2023: Progress in Neurobiology
Jiahui Ma, Xiaoling Huang, Zhenxing Li, Saiying Wang, Xuebin Yan, Dong Huang, Haocheng Zhou
Exposure to light stimuli may trigger or exacerbate perception of pain, also known as a common yet debilitating symptom of photophobia in patient with chronic orofacial pain. Mechanism underlying this phenomenon of photic sensitization in neuropathic condition remains elusive. Here, we found that rats developed hypersensitivity to normal light illumination after establishment of chronic constriction injury of infraorbital nerve (ION-CCI) model, which can be attenuated by blocking the exposure of photic stimulation...
September 28, 2023: Progress in Neurobiology
Jan Spaas, Thibaux Van der Stede, Sarah de Jager, Annet van de Waterweg Berends, Assia Tiane, Hans Baelde, Shahid P Baba, Matthias Eckhardt, Esther Wolfs, Tim Vanmierlo, Niels Hellings, Bert O Eijnde, Wim Derave
Multiple sclerosis (MS) pathology features autoimmune-driven neuroinflammation, demyelination, and failed remyelination. Carnosine is a histidine-containing dipeptide (HCD) with pluripotent homeostatic properties that is able to improve outcomes in an animal MS model (EAE) when supplied exogenously. To uncover if endogenous carnosine is involved in, and protects against, MS-related neuroinflammation, demyelination or remyelination failure, we here studied the HCD-synthesizing enzyme carnosine synthase (CARNS1) in human MS lesions and two preclinical mouse MS models (EAE, cuprizone)...
September 27, 2023: Progress in Neurobiology
Veronica Verdile, Ramona Palombo, Gabriele Ferrante, Alberto Ferri, Susanna Amadio, Cinzia Volonté, Maria Paola Paronetto
Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by the degeneration of upper and lower motor neurons, progressive wasting and paralysis of voluntary muscles. A hallmark of ALS is the frequent nuclear loss and cytoplasmic accumulation of RNA binding proteins (RBPs) in motor neurons (MN), which leads to aberrant alternative splicing regulation. However, whether altered splicing patterns are also present in familial models of ALS without mutations in RBP-encoding genes has not been investigated yet...
September 20, 2023: Progress in Neurobiology
Peiwu Ye, Qiuyuan Fang, Xupang Hu, Wenjuan Zou, Miaodan Huang, Minjing Ke, Yunhao Li, Min Liu, Xiaobo Cai, Congyi Zhang, Ning Hua, Umar Al-Sheikh, Xingyu Liu, Peilin Yu, Peiran Jiang, Ping-Yue Pan, Jianhong Luo, Lin-Hua Jiang, Suhong Xu, Evandro F Fang, Huanxing Su, Lijun Kang, Wei Yang
Different dopaminergic (DA) neuronal subgroups exhibit distinct vulnerability to stress, while the underlying mechanisms are elusive. Here we report that the transient receptor potential melastatin 2 (TRPM2) channel is preferentially expressed in vulnerable DA neuronal subgroups, which correlates positively with aging in Parkinson's Disease (PD) patients. Overexpression of human TRPM2 in the DA neurons of C. elegans resulted in selective death of ADE but not CEP neurons in aged worms. Mechanistically, TRPM2 activation mediates FZO-1/CED-9-dependent mitochondrial hyperfusion and mitochondrial permeability transition (MPT), leading to ADE death...
September 20, 2023: Progress in Neurobiology
Ehsan Shokri-Kojori, Dardo Tomasi, Sukru B Demiral, Gene-Jack Wang, Nora D Volkow
The relevance of interactions between autonomic and central nervous systems remains unclear for human brain function and health, particularly when both systems are challenged under sleep deprivation (SD). We measured brain activity (with fMRI), pulse and respiratory signals, and baseline brain amyloid beta burden (with PET) in healthy participants. We found that SD relative to rested wakefulness (RW) resulted in a significant increase in synchronized low frequency (LF, < 0.1 Hz) activity in an autonomically-related network (AN), including dorsal attention, visual, and sensorimotor regions, which we previously found to have consistent temporal coupling with LF pulse signal changes (regulated by sympathetic tone)...
October 2023: Progress in Neurobiology
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