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Ca2+ influx into excitable cells is a prerequisite for neurotransmitter release and regulated exocytosis. Within the group of ten cloned voltage-gated Ca2+ channels, the Cav2.3-containing E-type Ca2+ channels are involved in various physiological processes, such as neurotransmitter release and exocytosis together with other voltage-gated Ca2+ channels of the Cav1, Cav2 and Cav3 subfamily. However, E-type Ca2+ channels also exhibit several subunit-specific features, most of which still remain poorly understood. Cav2.3-containing R-type channels (here called‘E-type channels’) are also located in presynaptic terminals and interact with some synaptic vesicle proteins, the so-called SNARE proteins, although lacking the classical synprint interaction site. E-type channels trigger exocytosis and are also involved in long-term potentiation. Recently, it was shown that the interaction of Cav2.3 with the EF-hand motif containing protein EFHC1 is involved in the aetiology and pathogenesis of juvenile myoclonic epilepsy. [ABSTRACT FROM AUTHOR]

Abstract: Hippocampal theta oscillations are key elements in numerous behavioral and cognitive processes. Based on the dualistic theory of theta oscillations, one can differentiate between atropine-sensitive and atropine-insensitive theta subtypes. Urethane-induced atropine-sensitive theta oscillations are driven by muscarinic signal transduction pathways through G protein q/11 alpha subunit (Gαq/11), phospholipase β1/4 (PLCβ1/4), inositol trisphosphate (InsP3), diacylglycerole (DAG), and protein kinase C (PKC). Recent findings illustrate that Cav2.3 Ca2+ channels are important targets of muscarinic signaling in the hippocampus mediating plateau potential generation, epileptiform burst activity, and complex rhythm generation in the septohippocampal network. To investigate the physiological implications of Cav2.3 Ca2+ channels in hippocampal theta oscillations we performed radiotelemetric intrahippocampal (cornu ammonis (CA1)) recordings in urethane (800 mg/kg, i.p.) and atropine (50 mg/kg, i.p.) treated Cav2.3+/+ and Cav2.3−/− mice followed by wavelet analysis of EEG data. Our results demonstrate that Cav2.3 ablation, unlike PLCβ1 deletion, does not result in complete abolishment of urethane-induced theta oscillations and that both mean and total theta duration is not significantly inhibited by subsequent atropine treatment, indicating that Cav2.3 Ca2+ channels are important mediators of atropine-sensitive theta. Although theta frequency remained unchanged between both genotypes, the temporal characteristics of theta distribution, that is, theta architecture were significantly affected by the loss of Cav2.3 Ca2+ channels. Our data suggest, for the first time, that Cav2.3 voltage-gated Ca2+ channels (VGCC) are an important factor in septohippocampal synchronization associated with theta oscillation. [Copyright &y& Elsevier]

Although several adult rat models of medial temporal lobe epilepsy (mTLE) have been described in detail, our knowledge of mTLE epileptogenesis in infant rats is limited. Here, we present a novel infant rat model of mTLE (InfRPil-mTLE) based on a repetitive, triphasic injection regimen consisting of low-dose pilocarpine administrations (180 mg/kg. i.p.) on days 9, 11, and 15 post partum (pp). The model had a survival rate of >80% and exhibited characteristic spontaneous recurrent electrographic seizures (SRES) in both the hippocampus and cortex that persisted into adulthood. Using implantable video-EEG radiotelemetry, we quantified a complex set of seizure parameters that demonstrated the induction of chronic electroencephalographic seizure activity in our InfRPil-mTLE model, which predominated during the dark cycle. We further analyzed selected candidate genes potentially relevant to epileptogenesis using a RT-qPCR approach. Several candidates, such as the low-voltage-activated Ca 2+ channel Ca v 3.2 and the auxiliary subunits β 1 and β 2 2.3, M v , and M v 2.3, M 1 , and M 3 ) in the hippocampus and cortex of our InfRPil-mTLE model. From a translational point of view, our model could serve as a blueprint for childhood epileptic disorders and further contribute to antiepileptic drug research and development in the future., Competing Interests: The corresponding author and the co-authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2024 Carola Wormuth et al.)

Objectives: The G72 mouse model of schizophrenia represents a well-known model that was generated to meet the main translational criteria of isomorphism, homology and predictability of schizophrenia to a maximum extent. In order to get a more detailed view of the complex etiopathogenesis of schizophrenia, whole genome transcriptome studies turn out to be indispensable. Here we carried out microarray data collection based on RNA extracted from the retrosplenial cortex, hippocampus and thalamus of G72 transgenic and wild-type control mice. Experimental animals were age-matched and importantly, both sexes were considered separately., Data Description: The isolated RNA from all three brain regions was purified, quantified und quality controlled before initiation of the hybridization procedure with SurePrint G3 Mouse Gene Expression v2 8  ×  60 K microarrays. Following immunofluorescent measurement und preprocessing of image data, raw transcriptome data from G72 mice and control animals were extracted and uploaded in a public database. Our data allow insight into significant alterations in gene transcript levels in G72 mice and enable the reader/user to perform further complex analyses to identify potential age-, sex- and brain-region-specific alterations in transcription profiles and related pathways. The latter could facilitate biomarker identification and drug research and development in schizophrenia research., (© 2024. The Author(s).)

A variety of Alzheimer's disease (AD) mouse models has been established and characterized within the last decades. To get an integrative view of the sophisticated etiopathogenesis of AD, whole genome transcriptome studies turned out to be indispensable. Here we carried out microarray data collection based on RNA extracted from the retrosplenial cortex and hippocampus of age-matched, eight months old male and female APP/PS1 AD mice and control animals to perform sex- and brain region specific analysis of transcriptome profiles. The results of our studies reveal novel, detailed insight into differentially expressed signature genes and related fold changes in the individual APP/PS1 subgroups. Gene ontology and Venn analysis unmasked that intersectional, upregulated genes were predominantly involved in, e.g., activation of microglial, astrocytic and neutrophilic cells, innate immune response/immune effector response, neuroinflammation, phagosome/proteasome activation, and synaptic transmission. The number of (intersectional) downregulated genes was substantially less in the different subgroups and related GO categories included, e.g., the synaptic vesicle docking/fusion machinery, synaptic transmission, rRNA processing, ubiquitination, proteasome degradation, histone modification and cellular senescence. Importantly, this is the first study to systematically unravel sex- and brain region-specific transcriptome fingerprints/signature genes in APP/PS1 mice. The latter will be of central relevance in future preclinical and clinical AD related studies, biomarker characterization and personalized medicinal approaches., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Papazoglou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Melatonin supplementation strengthens non-restorative sleep rhythms and its temporal alignment in both humans and night-active rodents. Of note, although the sleep cycle is reversed in day-active and night-active (nocturnal) mammals, both, produce melatonin at night under the control of the circadian clock. The effects of exogenous melatonin on sleep and sleepiness are relatively clear, but its endogenous role in sleep, particularly, in timing sleep onset (SO), remains poorly understood. We show in nocturnal mice that the increases in mid-nighttime sleep episodes, and the mid-nighttime decline in activity, are coupled to nighttime melatonin signaling. Furthermore, we show that endogenous melatonin modulates SO by reducing the threshold for wake-to-sleep transitioning. Such link between melatonin and SO timing may explain phenomena such as increased sleep propensity in circadian rhythm sleep disorders and chronic insomnia in patients with severely reduced nocturnal melatonin levels. Our findings demonstrate that melatonin's role in sleep is evolutionarily conserved, effectively challenging the argument that melatonin cannot play a major role in sleep regulation in nocturnal mammals, where the main activity phase coincides with high melatonin levels., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)

A variety of Alzheimer disease (AD) mouse models has been established and characterized within the last decades. These models are generated to meet the principal criteria of AD isomorphism, homology and predictability to a maximum extent. To get an integrative view of the sophisticated etiopathogenesis of AD, whole genome transcriptome data analysis turns out to be indispensable. Here, we present a microarray-based transcriptome data collection based on RNA extracted from the retrosplenial (RS) cortex and the hippocampus of APP/PS1 AD mice and control animals. Experimental animals were age matched and importantly, both sexes were considered separately. Isolated RNA was purified, quantified und quality controlled prior to the hybridization procedure with SurePrint G3 Mouse Gene Expression v2 8 × 60K microarrays. Following immunofluorescent measurement und preprocessing/extraction of image data, raw transcriptome data were uploaded including differentially expressed gene candidates and related fold changes in APP/PS1 AD mice and controls. Our data allow further insight into alterations in gene transcript levels in APP/PS1 AD mice compared to controls and enable the reader/user to carry out complex transcriptome analysis to characterize potential age-, sex- and brain-region-specific alterations in e.g., neuroinflammatory, immunological, neurodegenerative and ion channel pathways., (© 2023 The Author(s).)

Current concepts regarding the biology of aging are primarily based on studies aimed at identifying factors regulating lifespan. However, lifespan as a sole proxy measure for aging can be of limited value because it may be restricted by specific pathologies. Here, we employ large-scale phenotyping to analyze hundreds of markers in aging male C57BL/6J mice. For each phenotype, we establish lifetime profiles to determine when age-dependent change is first detectable relative to the young adult baseline. We examine key lifespan regulators (putative anti-aging interventions; PAAIs) for a possible countering of aging. Importantly, unlike most previous studies, we include in our study design young treated groups of animals, subjected to PAAIs prior to the onset of detectable age-dependent phenotypic change. Many PAAI effects influence phenotypes long before the onset of detectable age-dependent change, but, importantly, do not alter the rate of phenotypic change. Hence, these PAAIs have limited effects on aging., (© 2022. The Author(s).)

Voltage-gated Ca 2+ channels (VGCCs) were reported to play a crucial role in neurotransmitter release, dendritic resonance phenomena and integration, and the regulation of gene expression. In the septohippocampal system, high- and low-voltage-activated (HVA, LVA) Ca 2+ channels were shown to be involved in theta genesis, learning, and memory processes. In particular, HVA Ca v 2.3 R-type and LVA Ca v 3 T-type Ca 2+ channels are expressed in the medial septum-diagonal band of Broca (MS-DBB), hippocampal interneurons, and pyramidal cells, and ablation of both channels was proven to severely modulate theta activity. Importantly, Ca v 3 Ca 2+ channels contribute to rebound burst firing in septal interneurons. Consequently, functional impairment of T-type Ca 2+ channels, e.g., in null mutant mouse models, caused tonic disinhibition of the septohippocampal pathway and subsequent enhancement of hippocampal theta activity. In addition, impairment of GABA A/B receptor transcription, trafficking, and membrane translocation was observed within the septohippocampal system. Given the recent findings that amyloid precursor protein (APP) forms complexes with GABA B receptors (GBRs), it is hypothesized that T-type Ca 2+ current reduction, decrease in GABA receptors, and APP destabilization generate complex functional interdependence that can constitute a sophisticated proamyloidogenic environment, which could be of potential relevance in the etiopathogenesis of Alzheimer's disease (AD). The age-related downregulation of T-type Ca 2+ channels in humans goes together with increased Aβ levels that could further inhibit T-type channels and aggravate the proamyloidogenic environment. The mechanistic model presented here sheds new light on recent reports about the potential risks of T-type Ca 2+ channel blockers (CCBs) in dementia, as observed upon antiepileptic drug application in the elderly.

The Electrophysiology Professional Interest Area (EPIA) and Global Brain Consortium endorsed recommendations on candidate electroencephalography (EEG) measures for Alzheimer's disease (AD) clinical trials. The Panel reviewed the field literature. As most consistent findings, AD patients with mild cognitive impairment and dementia showed abnormalities in peak frequency, power, and "interrelatedness" at posterior alpha (8-12 Hz) and widespread delta (< 4 Hz) and theta (4-8 Hz) rhythms in relation to disease progression and interventions. The following consensus statements were subscribed: (1) Standardization of instructions to patients, resting state EEG (rsEEG) recording methods, and selection of artifact-free rsEEG periods are needed; (2) power density and "interrelatedness" rsEEG measures (e.g., directed transfer function, phase lag index, linear lagged connectivity, etc.) at delta, theta, and alpha frequency bands may be use for stratification of AD patients and monitoring of disease progression and intervention; and (3) international multisectoral initiatives are mandatory for regulatory purposes., (© 2021 the Alzheimer's Association.)

High voltage-activated Ca v 2.3 R-type Ca 2+ channels and low voltage-activated Ca v 3.2 T-type Ca 2+ channels were reported to be involved in numerous physiological and pathophysiological processes. Many of these findings are based on studies in Ca v 2.3 and Ca v 3.2 deficient mice. Recently, it has been proposed that inbreeding of Ca v 2.3 and Ca v 3.2 deficient mice exhibits significant deviation from Mendelian inheritance and might be an indication for potential prenatal lethality in these lines. In our study, we analyzed 926 offspring from Ca v 3.2 breedings and 1142 offspring from Ca v 2.3 breedings. Our results demonstrate that breeding of Ca v 2.3 deficient mice shows typical Mendelian inheritance and that there is no indication of prenatal lethality. In contrast, Ca v 3.2 breeding exhibits a complex inheritance pattern. It might be speculated that the differences in inheritance, particularly for Ca v 2.3 breeding, are related to other factors, such as genetic specificities of the mutant lines, compensatory mechanisms and altered sperm activity.

This article provides raw relative electroencephalographic (EEG) power, temperature and activity data from controls and Ca v 3.2 deficient mice. Radiotransmitter implantation was carried out in male experimental mice under ketamine/xylazine narcosis. Following a recovery period, radiotelemetric EEG recordings from the hippocampal CA1 region were obtained under spontaneous 24 h long-term conditions and post urethane injection. Relative EEG power values (%) for 2 s epochs were analysed for the following frequency ranges: delta 1 ( δ 1 , 0.5-4 Hz), delta 2 ( δ 2 , 1-4 Hz), theta 1 ( θ 1 , 4-8 Hz), theta 2 ( θ 2 , 4-12 Hz), alpha ( α , 8-12 Hz), sigma ( σ , 12-16 Hz), beta 1 ( β 1 , 12-30 Hz), beta 2 ( β 2 , 16-24 Hz), beta 3 ( β 3 , 16-30 Hz), gamma low ( γ l o w , 30-50 Hz), gamma mid ( γ m i d , 50-70 Hz), gamma high ( γ h i g h , 70-100 Hz), gamma ripples ( γ r i p p l e s , 80-200 Hz), and gamma fast ripples ( γ f a s t r i p p l e s , 200-500 Hz). In addition, subcutaneous temperature and relative activity data were analysed for both the light and dark cycle of two long-term recordings. The same type of data was obtained post urethane injection. Detailed information is provided for the age and body weight of the experimental animals, the technical specifications of the radiofrequency transmitter, the stereotaxic coordinates for the intracerebral, deep and epidural, surface EEG electrodes, the electrode features, the filtering and sampling characteristics, the analysed EEG frequency bands and the data acquisition parameters. EEG power data, temperature and activity data are available at MENDELEY DATA (doi:10.17632/x53km5sby6.1, URL: http://dx.doi.org/10.17632/x53km5sby6.1). Raw EEG data are available at zenodo (https://zenodo.org/)., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships which have or could be perceived to have influenced the work reported in this article., (© 2021 The Authors. Published by Elsevier Inc.)

Recent pharmacoepidemiologic studies suggest that pharmacological neuroenhancement (pNE) and mood enhancement are globally expanding phenomena with distinctly different regional characteristics. Sociocultural and regulatory aspects, as well as health policies, play a central role in addition to medical care and prescription practices. The users mainly display self-involved motivations related to cognitive enhancement, emotional stability, and adaptivity. Natural stimulants, as well as drugs, represent substance abuse groups. The latter comprise purines, methylxanthines, phenylethylamines, modafinil, nootropics, antidepressants but also benzodiazepines, β -adrenoceptor antagonists, and cannabis. Predominant pharmacodynamic target structures of these substances are the noradrenergic/dopaminergic and cholinergic receptor/transporter systems. Further targets comprise adenosine, serotonin, and glutamate receptors. Meta-analyses of randomized-controlled studies in healthy individuals show no or very limited verifiability of positive effects of pNE on attention, vigilance, learning, and memory. Only some members of the substance abuse groups, i.e., phenylethylamines and modafinil, display positive effects on attention and vigilance that are comparable to caffeinated drinks. However, the development of new antidementia drugs will increase the availability and the potential abuse of pNE. Social education, restrictive regulatory measures, and consistent medical prescription practices are essential to restrict the phenomenon of neuroenhancement with its social, medical, and ethical implications. This review provides a comprehensive overview of the highly dynamic field of pharmacological neuroenhancement and elaborates the dramatic challenges for the medical, sociocultural, and ethical fundaments of society., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Johanna Daubner et al.)

T-type Ca 2+ channels are assumed to contribute to hippocampal theta oscillations. We used implantable video-EEG radiotelemetry and qPCR to unravel the role of Ca v 3.2 Ca 2+ channels in hippocampal theta genesis. Frequency analysis of spontaneous long-term recordings in controls and Ca v 3.2 -/- mice revealed robust increase in relative power in the theta (4-8 Hz) and theta-alpha (4-12 Hz) ranges, which was most prominent during the inactive stages of the dark cycles. Urethane injection experiments also showed enhanced type II theta activity and altered theta architecture following Ca v 3.2 ablation. Next, gene candidates from hippocampal transcriptome analysis of control and Ca v 3.2 -/- mice were evaluated using qPCR. Dynein light chain Tctex-Type 1 (Dynlt1b) was significantly reduced in Ca v 3.2 -/- mice. Furthermore, a significant reduction of GABA A receptor δ subunits and GABA B1 receptor subunits was observed in the septohippocampal GABAergic system. Our results demonstrate that ablation of Ca v 3.2 significantly alters type II theta activity and theta architecture. Transcriptional changes in synaptic transporter proteins and GABA receptors might be functionally linked to the electrophysiological phenotype.

Early pharmacoepidemiological studies suggested that Proton Pump Inhibitors (PPIs) might increase the risk of Alzheimer's Disease (AD) and non-AD related dementias. These findings were supported by preclinical studies, specifically stressing the proamyloidogenic and indirect anticholinergic effects of PPIs. However, further large-scale pharmacoepidemiological studies showed inconsistent results on the association between PPIs and dementia. Pharmacodynamically, these findings might be related to the LXR/RXR-mediated amyloid clearance effect and anti-inflammatory action of PPIs. Further aspects that influence PPI effects on AD are related to patient- specific pharmacokinetic and pharmacogenomic characteristics. In conclusion, a personalized (individualized) medicinal approach is necessary to model and predict the potential harmful or beneficial effects of PPIs in AD and non-AD-related dementias in the future., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Voltage-gated Ca 2+ channels (VGCCs) are considered to play a key role in auditory perception and information processing within the murine inner ear and brainstem. In the past, Ca v 1.3 L-type VGCCs gathered most attention as their ablation causes congenital deafness. However, isolated patch-clamp investigation and localization studies repetitively suggested that Ca v 2.3 R-type VGCCs are also expressed in the cochlea and further components of the ascending auditory tract, pointing to a potential functional role of Ca v 2.3 in hearing physiology. Thus, we performed auditory profiling of Ca v 2.3 +/+ controls, heterozygous Ca v 2.3 +/- mice and Ca v 2.3 null mutants (Ca v 2.3 -/- ) using brainstem-evoked response audiometry. Interestingly, click-evoked auditory brainstem responses (ABRs) revealed increased hearing thresholds in Ca v 2.3 +/- mice from both genders, whereas no alterations were observed in Ca v 2.3 -/- mice. Similar observations were made for tone burst-related ABRs in both genders. However, Ca v 2.3 ablation seemed to prevent mutant mice from total hearing loss particularly in the higher frequency range (36-42 kHz). Amplitude growth function analysis revealed, i.a., significant reduction in ABR wave W I and W III amplitude in mutant animals. In addition, alterations in W I -W IV interwave interval were observed in female Ca v 2.3 +/- mice whereas absolute latencies remained unchanged. In summary, our results demonstrate that Ca v 2.3 VGCCs are mandatory for physiological auditory information processing in the ascending auditory tract., (© 2019 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Electrophysiology provides a real-time readout of neural functions and network capability in different brain states, on temporal (fractions of milliseconds) and spatial (micro, meso, and macro) scales unmet by other methodologies. However, current international guidelines do not endorse the use of electroencephalographic (EEG)/magnetoencephalographic (MEG) biomarkers in clinical trials performed in patients with Alzheimer's disease (AD), despite a surge in recent validated evidence. This position paper of the ISTAART Electrophysiology Professional Interest Area endorses consolidated and translational electrophysiological techniques applied to both experimental animal models of AD and patients, to probe the effects of AD neuropathology (i.e., brain amyloidosis, tauopathy, and neurodegeneration) on neurophysiological mechanisms underpinning neural excitation/inhibition and neurotransmission as well as brain network dynamics, synchronization, and functional connectivity, reflecting thalamocortical and corticocortical residual capacity. Converging evidence shows relationships between abnormalities in EEG/MEG markers and cognitive deficits in groups of AD patients at different disease stages. The supporting evidence for the application of electrophysiology in AD clinical research as well as drug discovery pathways warrants an international initiative to include the use of EEG/MEG biomarkers in the main multicentric projects planned in AD patients, to produce conclusive findings challenging the present regulatory requirements and guidelines for AD studies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Voltage-gated Ca 2+ channels (VGCCs) play key roles in auditory perception and information processing within the inner ear and brainstem. Pharmacological inhibition of low voltage-activated (LVA) T-type Ca 2+ channels is related to both age- and noise induced hearing loss in experimental animals and may represent a promising approach to the treatment of auditory impairment of various etiologies. Within the LVA Ca 2+ channel subgroup, Ca v 3.2 is the most prominently expressed T-type channel entity in the cochlea and auditory brainstem. Thus, we performed a complete gender specific click and tone burst based auditory brainstem response (ABR) analysis of Ca v 3.2 +/- and Ca v 3.2 -/- mice, including i.a. temporal progression in hearing loss, amplitude growth function and wave latency analysis as well as a cochlear qPCR based evaluation of other VGCCs transcripts. Our results, based on a self-programmed automated wavelet approach, demonstrate that both heterozygous and Ca v 3.2 null mutant mice exhibit age-dependent increases in hearing thresholds at 5 months of age. In addition, complex alterations in W I-IV amplitudes and latencies were detected that were not attributable to alterations in the expression of other VGCCs in the auditory tract. Our results clearly demonstrate the important physiological role of Ca v 3.2 VGCCs in the spatiotemporal organization of auditory processing in young adult mice and suggest potential pharmacological targets for interventions in the future., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Brainstem evoked response audiometry (BERA) is of central relevance in the clinical neurophysiology. As other evoked potential (EP) techniques, such as visually evoked potentials (VEPs) or somatosensory evoked potentials (SEPs), the auditory evoked potentials (AEPs) are triggered by the repetitive presentation of identical stimuli, the electroencephalographic (EEG) response of which is subsequently averaged resulting in distinct positive (p) and negative (n) deflections. In humans, both the amplitude and the latency of individual peaks can be used to characterize alterations in synchronization and conduction velocity in the underlying neuronal circuitries. Importantly, AEPs are also applied in basic and preclinical science to identify and characterize the auditory function in pharmacological and genetic animal models. Even more, animal models in combination with pharmacological testing are utilized to investigate for potential benefits in the treatment of sensorineural hearing loss (e.g., age- or noise-induced hearing deficits). Here we provide a detailed and integrative description of how to record auditory brainstem-evoked responses (ABRs) in mice using click and tone-burst application. A specific focus of this protocol is on pre-experimental animal housing, anesthesia, ABR recording, ABR filtering processes, automated wavelet-based amplitude growth function analysis, and latency detection.

Objectives: Voltage-gated Ca 2+ channels (VGCCs) are of central relevance in regulating Ca 2+ influx into living cells. The low-voltage activated (LVA) Ca v 3 T-type Ca 2+ channels are widely distributed throughout the brain including the peripheral auditory system and ascending auditory tract. Their exact role in auditory information processing is still not fully understood. Within the LVA subgroup, Ca v 3.2 T-type Ca 2+ channels seem to be of special importance as qPCR revealed a steady increase in Ca v 3.2 transcript levels over age, e.g. in the cochlea and spiral ganglion neurons (SGN). Furthermore, pharmacological studies suggested an association between Ca v 3.2 expression and both age-related and noise-induced hearing loss. Given the potential functional relevance of Ca v 3.2 VGGCs in sensorineural hearing loss, we recorded gender specific auditory evoked brainstem responses (ABRs) upon both click and tone burst presentation. Here we present auditory brainstem response (ABR) data from Ca v 3.2 +/+ , Ca v 3.2 +/- and Ca v 3.2 -/- mice from both genders which are of value for researchers who want to evaluate how Ca v 3.2 loss affects basic auditory parameters, e.g. click and tone burst based hearing thresholds, amplitude growth function and peak latencies., Data Description: Information presented here includes ABR data from age-matched female and male Ca v 3.2 +/+ , Ca v 3.2 +/- and Ca v 3.2 -/- mice and technical aspects of the auditory recording protocol. Data were recorded using a commercially available ABR setup from Tucker Davis Technologies Inc. (TDT). Raw data files (arf.-file format) were exported as txt.-files with free access for analysis.

This data article provides raw auditory evoked brainstem responses (ABRs) from controls and Ca v 2.3 transgenics, i.e. heterozygous Ca v 2.3 +/- and Ca v 2.3 -/- null mutants. Gender specific ABR recordings were performed in age-matched animals under ketamine/xylazine narcosis. Data presented here include ABRs upon both click and tone burst presentation in the increasing SPL mode using a commercially available ABR setup from Tucker Davis Technologies Inc. (TDT, USA). Detailed information is provided for the sound attenuating cubicle, electrical shielding, electrode parameters, stimulus characteristics and architecture, sampling rate, filtering processes and ABR protocol application during the course of data acquisition and recording. The later are important for subsequent analysis of click and tone burst related hearing thresholds, amplitude growth function and peak latencies. Raw data are available at MENDELEY DATA, DIO: 〈DOI:10.17632/g6ygz2spzx.1〉, URL: 〈https://data.mendeley.com/datasets/g6ygz2spzx/1〉).

Advanced age is not only a major risk factor for a range of disorders within an aging individual but may also enhance susceptibility for disease in the next generation. In humans, advanced paternal age has been associated with increased risk for a number of diseases. Experiments in rodent models have provided initial evidence that paternal age can influence behavioral traits in offspring animals, but the overall scope and extent of paternal age effects on health and disease across the life span remain underexplored. Here, we report that old father offspring mice showed a reduced life span and an exacerbated development of aging traits compared with young father offspring mice. Genome-wide epigenetic analyses of sperm from aging males and old father offspring tissue identified differentially methylated promoters, enriched for genes involved in the regulation of evolutionarily conserved longevity pathways. Gene expression analyses, biochemical experiments, and functional studies revealed evidence for an overactive mTORC1 signaling pathway in old father offspring mice. Pharmacological mTOR inhibition during the course of normal aging ameliorated many of the aging traits that were exacerbated in old father offspring mice. These findings raise the possibility that inherited alterations in longevity pathways contribute to intergenerational effects of aging in old father offspring mice., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

Dietary restriction regimes extend lifespan in various animal models. Here we show that longevity in male C57BL/6J mice subjected to every-other-day feeding is associated with a delayed onset of neoplastic disease that naturally limits lifespan in these animals. We compare more than 200 phenotypes in over 20 tissues in aged animals fed with a lifelong every-other-day feeding or ad libitum access to food diet to determine whether molecular, cellular, physiological and histopathological aging features develop more slowly in every-other-day feeding mice than in controls. We also analyze the effects of every-other-day feeding on young mice on shorter-term every-other-day feeding or ad libitum to account for possible aging-independent restriction effects. Our large-scale analysis reveals overall only limited evidence for a retardation of the aging rate in every-other-day feeding mice. The data indicate that every-other-day feeding-induced longevity is sufficiently explained by delays in life-limiting neoplastic disorders and is not associated with a more general slowing of the aging process in mice.Dietary restriction can extend the life of various model organisms. Here, Xie et al. show that intermittent periods of fasting achieved through every-other-day feeding protect mice against neoplastic disease but do not broadly delay organismal aging in animals.

Maternal folic acid (FA) supplementation prior to and during gestation is recommended for the prevention of neural tube closure defects in the developing embryo. Prior studies, however, suggested that excessive FA supplementation during gestation can be associated with toxic effects on the developing organism. Here, we address whether maternal dietary folic acid supplementation at 40 mg/kg chow (FD), restricted to a period prior to conception, affects neurobehavioural development in the offspring generation. Detailed behavioural analyses showed reversal learning impairments in the Morris water maze in offspring derived from dams exposed to FD prior to conceiving. Furthermore, offspring of FD dams showed minor and transient gene expression differences relative to controls. Our data suggest that temporary exposure of female germ cells to FD is sufficient to cause impaired cognitive flexibility in the subsequent generation.

Pharmacological neuroenhancement and mood enhancement are gaining tremendous importance in society. The main motivation for neuroenhancement and mood enhancement is the anticipated increase in attention and vigilance, better performance in learning and memory and mood stability to meet the complex demands of an exacerbating meritocracy. Most users apply drugs originally designated for attention disorders, sleep disorders or dementia. Application of related drugs in terms of enhancement strategies in healthy individuals is off-label per se, the acquisition and distribution illegal. Here, we first provide an overview of the basic physiological mechanisms underlying vigilance, learning and memory, and emotional states. We then present the different pharmacological classes, i. a. purines and methylxanthines, phenylethylamine, modafinil, nootropics and antidepressants and elaborate their pharmacodynamics profile. Special attention will be paid to the norepinephrine/dopamine and cholinergic receptors and transporter systems but also to functional interaction with adenosine, serotonine and the glutamate receptor systems. Metaanalysis revealed that efficacy reported in, e. g. ADHD or dementia patients cannot be translated to healthy individuals. A validated positive effect on attention and vigilance has only been reported for some phenylethylamines and modafinil. It is likely that new developments, particularly in the field of antidementives will dramatically enhance neuroenhancement and mood enhancement. Drug regulatory actions, public and political discussions are necessary to meet the ethical and legal challenges of neuroenhancement and mood enhancement in the future.

Voltage-gated Ca 2+ channels are of central relevance in mediating numerous intracellular and transcellular processes including excitation-contraction coupling, excitation secretion-coupling, hormone and neurotransmitter release and gene expression. The Ca v 2.3 R-type Ca 2+ channel is a high-voltage activated channel which plays a crucial role in neurotransmitter release, long-term potentiation and hormone release. Furthermore, Ca v 2.3 R-type channels were reported to be involved in ictogenesis, epileptogenesis, fear behavior, sleep, pre-and postsynaptic integration and rhythmicity within the hippocampus. Ca v 3 T-type Ca 2+ channels are low-voltage activated and also widely expressed throughout the brain enabling neurons to switch between different firing patterns and to modulate burst activity. Disruption of T-type Ca 2+ current has been related to sleep disorders, epilepsy, Parkinson׳s disease, depression, schizophrenia and pain. Ca v 3.2 ablation was further attributed to elevated anxiety and hippocampal alterations resulting in impaired long-term potentiation and memory. Given the importance of Ca v 2.3 and Ca v 3.2 voltage-gated Ca 2+ channels within the CNS, particularly the hippocampus, we collected gender specific microarray transcriptome data of murine hippocampal RNA probes using the Affymetrix Exon Expression Chip Mouse Gene 1.0 ST v1. Information presented here includes transcriptome data from Ca v 2.3 +/+ , Ca v 2.3 +/- , Ca v 2.3 -/- , Ca v 3.2 +/+ , Ca v 3.2 +/- and Ca v 3.2 -/- mice from both genders, the protocol and list of primers used for genotyping animals, the hippocampal RNA isolation procedure and quality controls.

Theta activity is generated in the septohippocampal system and can be recorded using deep intrahippocampal electrodes and implantable electroencephalography (EEG) radiotelemetry or tether system approaches. Pharmacologically, hippocampal theta is heterogeneous (see dualistic theory) and can be differentiated into type I and type II theta. These individual EEG subtypes are related to specific cognitive and behavioral states, such as arousal, exploration, learning and memory, higher integrative functions, etc. In neurodegenerative diseases such as Alzheimer's, structural and functional alterations of the septohippocampal system can result in impaired theta activity/oscillations. A standard quantitative analysis of the hippocampal EEG includes a Fast-Fourier-Transformation (FFT)-based frequency analysis. However, this procedure does not provide details about theta activity in general and highly-organized theta oscillations in particular. In order to obtain detailed information on highly-organized theta oscillations in the hippocampus, we have developed a new analytical approach. This approach allows for time- and cost-effective quantification of the duration of highly-organized theta oscillations and their frequency characteristics.

Alzheimer's disease (AD) is a multifactorial disorder leading to progressive memory loss and eventually death. In this study, an APPswePS1dE9 AD mouse model has been analyzed for motor cortex theta, beta and gamma frequency alterations using computerized 3D stereotaxic electrode positioning and implantable video-EEG radiotelemetry to perform long-term M1 recordings from both genders considering age, circadian rhythm and activity status of experimental animals. We previously demonstrated that APPswePS1dE9 mice exibit complex alterations in hippocampal frequency power and another recent investigation reported a global increase of alpha, beta and gamma power in APPswePS1dE9 in females of 16-17 weeks of age. In this cortical study in APPswePS1dE9 mice we did not observe any changes in theta, beta and particularly gamma power in both genders at the age of 14, 15, 18 and 19 weeks. Importantly, no activity dependence of theta, beta and gamma activity could be detected. These findings clearly point to the fact that EEG activity, particularly gamma power exhibits developmental changes and spatial distinctiveness in the APPswePS1dE9 mouse model of Alzheimer's disease., Competing Interests: The authors have declared that no competing interests exist.

Background: Researchers have gained substantial insight into mechanisms of synaptic transmission, hyperexcitability, excitotoxicity and neurodegeneration within the last decades. Voltage-gated Ca 2+ channels are of central relevance in these processes. In particular, they are key elements in the etiopathogenesis of numerous seizure types and epilepsies. Earlier studies predominantly targeted on Ca v 2.1 P/Q-type and Ca v 3.2 T-type Ca 2+ channels relevant for absence epileptogenesis. Recent findings bring other channels entities more into focus such as the Ca v 2.3 R-type Ca 2+ channel which exhibits an intriguing role in ictogenesis and seizure propagation. Ca v 2.3 R-type voltage gated Ca 2+ channels (VGCC) emerged to be important factors in the pathogenesis of absence epilepsy, human juvenile myoclonic epilepsy (JME), and cellular epileptiform activity, e.g . in CA1 neurons. They also serve as potential target for various antiepileptic drugs, such as lamotrigine and topiramate., Objective: This review provides a summary of structure, function and pharmacology of VGCCs and their fundamental role in cellular Ca 2+ homeostasis. We elaborate the unique modulatory properties of Ca v 2.3 R-type Ca 2+ channels and point to recent findings in the proictogenic and proneuroapoptotic role of Ca v 2.3 R-type VGCCs in generalized convulsive tonic-clonic and complex-partial hippocampal seizures and its role in non-convulsive absence like seizure activity., Conclusion: Development of novel Ca v 2.3 specific modulators can be effective in the pharmacological treatment of epilepsies and other neurological disorders.

This submission contains a commentary., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Implantable EEG radiotelemetry is of central relevance in the neurological characterization of transgenic mouse models of neuropsychiatric and neurodegenerative diseases as well as epilepsies. This powerful technique does not only provide valuable insights into the underlying pathophysiological mechanisms, i.e., the etiopathogenesis of CNS related diseases, it also facilitates the development of new translational, i.e., therapeutic approaches. Whereas competing techniques that make use of recorder systems used in jackets or tethered systems suffer from their unphysiological restraining to semi-restraining character, radiotelemetric EEG recordings overcome these disadvantages. Technically, implantable EEG radiotelemetry allows for precise and highly sensitive measurement of epidural and deep, intracerebral EEGs under various physiological and pathophysiological conditions. First, we present a detailed protocol of a straight forward, successful, quick and efficient technique for epidural (surface) EEG recordings resulting in high-quality electrocorticograms. Second, we demonstrate how to implant deep, intracerebral EEG electrodes, e.g., in the hippocampus (electrohippocampogram). For both approaches, a computerized 3D stereotaxic electrode implantation system is used. The radiofrequency transmitter itself is implanted into a subcutaneous pouch in both mice and rats. Special attention also has to be paid to pre-, peri- and postoperative treatment of the experimental animals. Preoperative preparation of mice and rats, suitable anesthesia as well as postoperative treatment and pain management are described in detail.