The innate fear response is an emotional response that does not require any previously acquired conditioning. One of the standard methods to analyze the innate fear response is a ...2,4,5-trimethylthiazoline (TMT)-induced freezing test. TMT is an odor originally isolated from anal secretion of the red fox. Acute TMT exposure has been shown to induce robust freezing behavior in rats and mice (Wallace and Rosen, 2000; Galliot
, 2012 ). Here, I show how to expose mice to TMT and how to analyze their freezing behavior.
Neuronal synapses undergo structural and functional changes throughout life, which are essential for nervous system physiology. However, these changes may also perturb the excitatory-inhibitory ...neurotransmission balance and trigger neuropsychiatric and neurological disorders. Molecular tools to restore this balance are highly desirable. Here, we designed and characterized CPTX, a synthetic synaptic organizer combining structural elements from cerebellin-1 and neuronal pentraxin-1. CPTX can interact with presynaptic neurexins and postsynaptic AMPA-type ionotropic glutamate receptors and induced the formation of excitatory synapses both in vitro and in vivo. CPTX restored synaptic functions, motor coordination, spatial and contextual memories, and locomotion in mouse models for cerebellar ataxia, Alzheimer's disease, and spinal cord injury, respectively. Thus, CPTX represents a prototype for structure-guided biologics that can efficiently repair or remodel neuronal circuits.
The cerebellum is thought to be involved in cognitive functions in addition to its well established role in motor coordination and motor learning in humans. Cerebellin 1 (Cbln1) is predominantly ...expressed in cerebellar granule cells and plays a crucial role in the formation and function of parallel fiber-Purkinje cell synapses. Although genes encoding Cbln1 and its postsynaptic receptor, the delta2 glutamate receptor (GluD2), are suggested to be associated with autistic-like traits and many psychiatric disorders, whether such cognitive impairments are caused by cerebellar dysfunction remains unclear. In the present study, we investigated whether and how Cbln1 signaling is involved in non-motor functions in adult mice. We show that acquisition and retention/retrieval of cued and contextual fear memory were impaired in Cbln1-null mice. In situ hybridization and immunohistochemical analyses revealed that Cbln1 is expressed in various extracerebellar regions, including the retrosplenial granular cortex and the hippocampus. In the hippocampus, Cbln1 immunoreactivity was present at the molecular layer of the dentate gyrus and the stratum lacunosum-moleculare without overt mRNA expression, suggesting that Cbln1 is provided by perforant path fibers. Retention/retrieval, but not acquisition, of cued and contextual fear memory was impaired in forebrain-predominant Cbln1-null mice. Spatial learning in the radial arm water maze was also abrogated. In contrast, acquisition of fear memory was affected in cerebellum-predominant Cbln1-null mice. These results indicate that Cbln1 in the forebrain and cerebellum mediates specific aspects of fear conditioning and spatial memory differentially and that Cbln1 signaling likely regulates motor and non-motor functions in multiple brain regions.
Despites its well known role in motor coordination and motor learning, whether and how the cerebellum is involved in cognitive functions remains less clear. Cerebellin 1 (Cbln1) is highly expressed in the cerebellum and serves as an essential synaptic organizer. Although genes encoding Cbln1 and its receptor are associated with many psychiatric disorders, it remains unknown whether such cognitive impairments are caused by cerebellar dysfunction. Here, we show that Cbln1 is also expressed in the forebrain, including the hippocampus and retrosplenial granular cortex. Using forebrain- and cerebellum-predominant conditional Cbln1-null mice, we show that Cbln1 in the forebrain and cerebellum mediates specific aspects of fear conditioning and spatial memory differentially, indicating that Cbln1 signaling regulates both motor and non-motor functions in multiple brain regions.
There is a question whether the conductive filament (CF) formed in the oxide layer of a resistive-switching random access memory is made of oxygen vacancies or metallic atoms. We investigated the CF ...of Ni/TiO
2
/Pt device using temperature coefficient of resistance (TCR), anisotropic magnetoresistance (AMR), and cross-sectional transmission electron microscopy with energy dispersive X-ray analysis (TEM-EDX). The low resistance state (LRS) of the device showed metallic property by TCR measurement. Furthermore, the device in the LRS showed AMR, which was a direct evidence of the formation of ferromagnetic CF. The cross-sectional TEM-EDX observation revealed that a nano-sized Ni precipitation existed in the area nearby a conductive spot. It is intensively suggested that Ni atoms migrated from the adjacent Ni electrode to TiO
2
layer to form the nano-sized ferromagnetic CF.
Long-term synaptic plasticity at glutamatergic synapses on striatal spiny projection neurons (SPNs) is central to learning goal-directed behaviors and habits. Our studies reveal that SPNs manifest a ...heterosynaptic, nitric oxide (NO)-dependent form of long-term postsynaptic depression of glutamatergic SPN synapses (NO-LTD) that is preferentially engaged at quiescent synapses. Plasticity is gated by Ca2+ entry through CaV1.3 Ca2+ channels and phosphodiesterase 1 (PDE1) activation, which blunts intracellular cyclic guanosine monophosphate (cGMP) and NO signaling. Both experimental and simulation studies suggest that this Ca2+-dependent regulation of PDE1 activity allows for local regulation of dendritic cGMP signaling. In a mouse model of Parkinson disease (PD), NO-LTD is absent because of impaired interneuronal NO release; re-balancing intrastriatal neuromodulatory signaling restores NO release and NO-LTD. Taken together, these studies provide important insights into the mechanisms governing NO-LTD in SPNs and its role in psychomotor disorders such as PD.
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•cGMP-dependent LTD of striatal glutamatergic synapses was controlled by PDE1•The activity of PDE1 was regulated by Ca2+ influx through CaV1.3 Ca2+ channels•This coupling limited cGMP-dependent LTD to dendritic regions that were inactive•Reversing neuromodulatory imbalance restored cGMP-LTD in a Parkinson's disease model
Synaptic plasticity in the brain is generally considered to be dependent on elevated neuronal activity. Zhai et al. describe a heterosynaptic form of postsynaptic, long-term depression of glutamatergic synapses in striatal spiny projection neurons that is dependent on inactivity, making it a potential mechanism for “forgetting.”
Acoustic therapies including hearing aids and tinnitus control instruments are widely used in Japan but without high levels of evidence. The outpatient hearing aid clinic at our institution fits ...patients with hearing aids and instructs patients on how to use them to control tinnitus if present. In this study, we examined the effects of this approach on tinnitus.
One hundred and eleven of 138 patients who visited our hearing aid clinic from April 2016 to September 2018 purchased hearing aids after fitting. Sixty-six of these patients (31 men, 35 women; mean age 78.0 ± 8.0 years) had both hearing loss and tinnitus and were enrolled. The tinnitus was bilateral in 41 patients and unilateral in 25 (poor hearing ear, n = 16, good hearing ear, n = 9). Hearing aids were worn bilaterally by 23 patients and unilaterally by 43 (89 devices). Seventeen of the 23 patients wearing bilateral hearing aids had bilateral tinnitus and 6 had unilateral tinnitus, i.e., in 40 ears, the tinnitus side matched the hearing aid side (40 devices) and in 6 ears did not (6 devices). Twenty-four of 43 patients wearing unilateral hearing aids had bilateral tinnitus, meaning that in 24 ears the tinnitus side matched the hearing aid side (24 devices). In six of the remaining 19 cases with unilateral tinnitus, the hearing aid and tinnitus were on the same side (6 devices) and in 13 were on opposite sides (13 devices). Changes in the Tinnitus Handicap Inventory (THI), visual analog scale (VAS, for tinnitus discomfort, severity, and persistence), and Hospital Anxiety and Depression Scale scores were measured immediately before using a hearing aid and 12 months later.
Significant effects of hearing aids on tinnitus were observed in all subjects (THI, p = 0.0000030), VAS (severity, p = 0.000000066; discomfort, p = 0.0000013). Significant effects were observed with bilateral hearing aids (THI, p = 0.0012; VAS for severity, p = 0.00069; VAS for discomfort, p = 0.00052) and with unilateral hearing aids (THI, p = 0.00055; VAS for severity, p = 0.000034; VAS for discomfort, p = 0.00007). Spearman's rank correlation coefficient showed a significant positive correlation between the THI and VAS scores (p = 0.0033). In cases of bilateral tinnitus, significant differences were observed with bilateral hearing aids (THI, p = 0.011; VAS for severity, p = 0.0019; VAS for discomfort; p = 0.020) and with unilateral hearing aids (THI, p = 0.00069; VAS for severity, p = 0.00071; VAS for discomfort, p = 0.000093).
Acoustic therapy using hearing aids was effective for tinnitus. Even when bilateral, a unilateral hearing aid is able to improve tinnitus. When unilateral, the ipsilateral hearing aid is able to improve tinnitus.
Congenital cytomegalovirus (cCMV) infection is the most common congenital viral infection and is the leading non‐genetic cause of sensorineural hearing loss and an important cause of ...neurodevelopmental disabilities. Auto auditory brainstem response (AABR) is a simple hearing test and used for the purpose of neonatal hearing screening, but can use it for early detection hard of hearing within the study age of the model. We experienced two case of asymptomatic CMV infection in which congenital and late‐onset hearing loss were diagnosed early with AABR, and hearing loss improved with valganciclovir.
Highlights • Status epilepticus was induced for 1.5 and 4.5 h in a pilocarpine mouse model. • Anxiety-related behavior depended on status epilepticus duration. • Hippocampal BDNF levels were ...correlated with anxiety-related behavior. • BDNF in the hippocampus might cause anxiety-related behavior in adulthood.
Highlights • Long-term continuous video-EEG recording was performed with SNAP-25 knock-in mice. • A variety of epileptic seizures and discharges was observed in an ordered sequence. • A variety of ...progressive EEG changes was observed over 10 weeks. • Anxiety-like behavior appeared within a few days after multiple seizures. • Several changes with different time courses occurred in parallel in the brain.
•Parasitic resistance and its variability are obstacles for the scaling of FinFETs.•Reducing the fin thickness degrades in parasitic resistance and its variability.•Implantation of As instead of P ...for the extension doping causes the same effect.•These phenomena are observed to be caused by residual defects in the crystalline fin.
The influence of extension doping on parasitic resistance and its variability has been investigated for FinFETs. Electrical characterization of FinFETs and crystallinity evaluation of the doped fin structure are carried out for different fin thicknesses and different donor species for ion implantation, i.e., As and P. Reducing the fin thickness and the use of donor species with a larger mass cause serious degradation in the variability and median value of the parasitic resistance. Crystallinity evaluation by transmission electron microscope reveals that significant crystal defects remain after dopant activation annealing for the cases of smaller fin thickness and the implanted dopant with a larger mass. The unrecovered defects cause serious degradation in the parasitic resistance and its variability.
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