Acquisition phase-specific contribution of climbing fiber transmission to cerebellum-dependent motor memory in mice.

Climbing fiber (CF) transmission from the inferior olive (IO) triggers complex spikes (Cs) in Purkinje cells (PCs) driven by a burst of calcium spikes. In the context of motor learning, especially the compensatory optic response, CF transmission serves as an instructive signal selectively conveyed to PCs. While the significance of CF input in motor memory formation is widely acknowledged, a comprehensive understanding of its distinct contribution across different temporal windows, spanning from the initial learning phase to the retrieval period, remains incomplete.

Peripheral substance P induces deficits in hippocampal synaptic plasticity and memory.

Substance P (SP) is a neuropeptide that functions in both the central and peripheral nervous systems. Although the peripheral actions of SP in regulating inflammatory responses have been extensively investigated, the effects of elevated peripheral SP on hippocampal functions such as spatial learning and memory remains unclear, even though SP can cross the blood-brain barrier. In this study, we found that male mice subcutaneously injected with SP for 14 days exhibited significant deficits in hippocampus-dependent memory, as assessed by the object place recognition and novel object recognition tests.

A normative principle governing memory transfer in cerebellar motor learning.

The cerebellum, consisting of the cerebellar cortex and nuclei, plays a crucial role in motor learning and exhibits a phenomenon known as systems consolidation, where memory traces are transferred from the cortex to the nuclei. However, the underlying principles and mechanisms governing this memory transfer remain unclear. In this study, we propose a normative framework extending the bias-variance tradeoff that predicts task difficulty as a key factor regulating memory transfer.

Quantitative dynamics of neural uncertainty in sensory processing and decision-making during discriminative learning.

Uncertainty is crucial in sensory processing, necessitating further quantitative research on its neural representation in the sensory cortex. Here, to address this need, we used a deep learning approach to quantify uncertainties in neural activity from the forelimb area of the primary somatosensory cortex (fS1) during a vibration frequency discrimination task, introducing a transformer model designed to decode neural data not consistently tracked over time. Our model shows that the neural representation of fS1 encodes uncertainties not only from vibratory stimuli but also from decision-making processes, emphasizing its crucial role across various biological contexts.

Increased mGluR5 in somatostatin-positive interneurons mediates deactivation of the mPFC in a mouse model of neuropathic pain.

Understanding the neurobiological alterations associated with neuropathic pain is crucial for treatment interventions, but the underlying mechanisms remain unclear. We focused on the medial prefrontal cortex (mPFC), which undergoes various processes of plasticity during the development of neuropathic pain. In particular, in the neuropathic pain state, the pyramidal neuron activity is decreased and metabotropic glutamate receptor 5 (mGluR5) activity is increased in the mPFC.

Aberrant ERK signaling in astrocytes impairs learning and memory in RASopathy-associated BRAF mutant mouse models.

RAS/MAPK pathway mutations often induce RASopathies with overlapping features, such as craniofacial dysmorphology, cardiovascular defects, dermatologic abnormalities, and intellectual disabilities. Although B-Raf proto-oncogene (BRAF) mutations are associated with cardio-facio-cutaneous (CFC) syndrome and Noonan syndrome, it remains unclear how these mutations impair cognition. Here, we investigated the underlying neural mechanisms using several mouse models harboring a gain-of-function BRAF mutation (K499E) discovered in RASopathy patients.

Cerebellar Bergmann glia integrate noxious information and modulate nocifensive behaviors.

The cerebellum is activated by noxious stimuli and pathological pain but its role in noxious information processing remains unknown. Here, we show that in mice, cutaneous noxious electrical stimuli induced noradrenaline (NA) release from locus coeruleus (LC) terminals in the cerebellar cortex. Bergmann glia (BG) accumulated these LC-NA signals by increasing intracellular calcium in an integrative manner ('flares').

CB1R activates the epilepsy-associated protein Go to regulate neurotransmitter release and synaptic plasticity in the cerebellum.

encodes the alpha subunit of the heterotrimeric Go protein. Despite being the most abundant G protein at synapses, the role of Go in the brain remains unclear, primarily because of the high mortality associated with developmental and epileptic encephalopathy (DEE) 17 in mutated animals. Here, we conducted proteomic analyses with a brain synaptosomal fraction to investigate the Go-interactome and then generated a non-DEE model using mice to selectively knockout (KO) the presynaptic Gαo within cerebellum.

Differentiating visceral sensory ganglion organoids from induced pluripotent stem cells.

The ability to generate visceral sensory neurons (VSN) from induced pluripotent stem (iPS) cells may help to gain insights into how the gut-nerve-brain axis is involved in neurological disorders. We established a protocol to differentiate human iPS-cell-derived visceral sensory ganglion organoids (VSGOs). VSGOs exhibit canonical VSN markers, and single-cell RNA sequencing revealed heterogenous molecular signatures and developmental trajectories of VSGOs aligned with native VSN.

Activity in the dorsal hippocampus-mPFC circuit modulates stress-coping strategies during inescapable stress.

Anatomical connectivity and lesion-deficit studies have shown that the dorsal and ventral hippocampi contribute to cognitive and emotional processes, respectively. However, the role of the dorsal hippocampus (dHP) in emotional or stress-related behaviors remains unclear. Here, we showed that neuronal activity in the dHP affects stress-coping behaviors in mice via excitatory projections to the medial prefrontal cortex (mPFC).

Corrigendum: Localization of hyperpolarization-activated cyclic nucleotide-gated channels in the vertebrate retinas across species and their physiological roles.

[This corrects the article DOI: 10.3389/fnana.2024.

Localization of hyperpolarization-activated cyclic nucleotide-gated channels in the vertebrate retinas across species and their physiological roles.

Transmembrane proteins known as hyperpolarization-activated cyclic nucleotide-gated (HCN) channels control the movement of Na and K ions across cellular membranes. HCN channels are known to be involved in crucial physiological functions in regulating neuronal excitability and rhythmicity, and pacemaker activity in the heart. Although HCN channels have been relatively well investigated in the brain, their distribution and function in the retina have received less attention, remaining their physiological roles to be comprehensively understood.

Dual effects of TGF-β inhibitor in ALS - inhibit contracture and neurodegeneration.

As persistent elevation of transforming growth factor-β (TGF-β) promotes fibrosis of muscles and joints and accelerates disease progression in amyotrophic lateral sclerosis (ALS), we investigated whether inhibition of TGF-β would be effective against both exacerbations. The effects of TGF-β and its inhibitor on myoblasts and fibroblasts were tested in vitro and confirmed in vivo, and the dual action of a TGF-β inhibitor in ameliorating the pathogenic role of TGF-β in ALS mice was identified. In the peripheral neuromuscular system, fibrosis in the muscles and joint cavities induced by excessive TGF-β causes joint contracture and muscular degeneration, which leads to motor dysfunction.

Machine learning-based evaluation of spontaneous pain and analgesics from cellular calcium signals in the mouse primary somatosensory cortex using explainable features.

Introduction: Pain that arises spontaneously is considered more clinically relevant than pain evoked by external stimuli. However, measuring spontaneous pain in animal models in preclinical studies is challenging due to methodological limitations. To address this issue, recently we developed a deep learning (DL) model to assess spontaneous pain using cellular calcium signals of the primary somatosensory cortex (S1) in awake head-fixed mice.

Intrinsic plasticity of Purkinje cell serves homeostatic regulation of fear memory.

Two forms of plasticity, synaptic and intrinsic, are neural substrates for learning and memory. Abnormalities in homeostatic plasticity cause severe neuropsychiatric diseases, such as schizophrenia and autism. This suggests that the balance between synaptic transmission and intrinsic excitability is important for physiological function in the brain.

α-Synuclein propagation leads to synaptic abnormalities in the cortex through microglial synapse phagocytosis.

The major neuropathologic feature of Parkinson's disease is the presence of widespread intracellular inclusions of α-synuclein known as Lewy bodies. Evidence suggests that these misfolded protein inclusions spread through the brain with disease progression. Changes in synaptic function precede neurodegeneration, and this extracellular α-synuclein can affect synaptic transmission.

Dynamic alteration of intrinsic properties of the cerebellar Purkinje cell during the motor memory consolidation.

Intrinsic plasticity of the cerebellar Purkinje cell (PC) plays a critical role in motor memory consolidation. However, detailed changes in their intrinsic properties during memory consolidation are not well understood. Here, we report alterations in various properties involved in intrinsic excitability, such as the action potential (AP) threshold, AP width, afterhyperpolarization (AHP), and sag voltage, which are associated with the long-term depression of intrinsic excitability following the motor memory consolidation process.

mGluR1 Regulates the Interspike Interval Threshold for Dendritic Ca Transients in the Cerebellar Purkinje Cells.

Ca+ transients can be observed in the distal dendrites of Purkinje cells (PCs) despite their lack of action potential backpropagation. These Ca+ events in distal dendrites require specific patterns of PC firing, such as complex spikes (CS) or simple spikes (SS) of burst mode. Unlike CS, which can act directly on voltage-gated calcium channels in the dendrites through climbing fiber inputs, the condition that can produce the Ca+ events in distal dendrites with burst mode SS is poorly understood.

Effect of a differential training paradigm with varying frequencies and amplitudes on adaptation of vestibulo-ocular reflex in mice.

The vestibulo-ocular reflex (VOR) functions to maintain eye stability during head movement, and VOR gain can be dynamically increased or decreased by gain-up or gain-down adaptation. In this study, we investigated the impact of a differential training paradigm with varying frequencies and amplitudes on the level of VOR adaptation in mice. Training for gain-up (out of phase) or gain-down (in phase) VOR adaptation was applied for 60 min using two protocols: (1) oscillation of a drum and turntable with fixed frequency and differing amplitudes (0.

Cerebellar nuclei neurons projecting to the lateral parabrachial nucleus modulate classical fear conditioning.

Multiple brain regions are engaged in classical fear conditioning. Despite evidence for cerebellar involvement in fear conditioning, the mechanisms by which cerebellar outputs modulate fear learning and memory remain unclear. We identify a population of deep cerebellar nucleus (DCN) neurons with monosynaptic glutamatergic projections to the lateral parabrachial nucleus (lPBN) (DCN neurons) in mice.

Lateral hypothalamic leptin receptor neurons drive hunger-gated food-seeking and consummatory behaviours in male mice.

For survival, it is crucial for eating behaviours to be sequenced through two distinct seeking and consummatory phases. Heterogeneous lateral hypothalamus (LH) neurons are known to regulate motivated behaviours, yet which subpopulation drives food seeking and consummatory behaviours have not been fully addressed. Here, in male mice, fibre photometry recordings demonstrated that LH leptin receptor (LepR) neurons are correlated explicitly in both voluntary seeking and consummatory behaviours.

Cerebellum as a kernel machine: A novel perspective on expansion recoding in granule cell layer.

Sensorimotor information provided by mossy fibers (MF) is mapped to high-dimensional space by a huge number of granule cells (GrC) in the cerebellar cortex's input layer. Significant studies have demonstrated the computational advantages and primary contributor of this expansion recoding. Here, we propose a novel perspective on the expansion recoding where each GrC serve as a kernel basis function, thereby the cerebellum can operate like a kernel machine that implicitly use high dimensional (even infinite) feature spaces.

Serum C3 complement levels predict prognosis and monitor disease activity in Guillain-Barré syndrome.

Objective: Biomarkers are needed to predict prognosis and disease activity in patients with Guillain-Barré syndrome (GBS). The complement system is a key player in the pathogenesis of GBS. This study aimed to assess the potential utility of serum complement proteins as novel biomarkers in GBS.

Multiplexed Representation of Itch and Pain and Their Interaction in the Primary Somatosensory Cortex.

Itch and pain are distinct sensations that share anatomically similar pathways: from the periphery to the brain. Over the last decades, several itch-specific neural pathways and molecular markers have been identified at the peripheral and spinal cord levels. Although the perception of sensation is ultimately generated at the brain level, how the brain separately processes the signals is unclear.