Background: In auditory behavioral and EEG experiments, the variability of stimulation solutions, for both software and hardware, adds unnecessary technical constraints. Currently, there is no easy to use, inexpensive and shareable solution that could improve collaborations and data comparisons across different sites and contexts. Method: This paper outlines a system composed by a Raspberry Pi coupled with Python programming and associated with a HifiBerry sound card. We compare its sound performances with those of a wide variety of material and configurations. This solution achieves the high timing accuracy and sound quality important in auditory cognition experiments, while being simple to use and open source. Results: The present system shows high performances and results along with excellent feedback from users. It is inexpensive, easy to build, share and improve-upon. Working with such low cost, powerful and collaborative hardware and software tools allow people to create their own specific, adapted...

Post tetanic potentiation (PTP) is a form of short-term plasticity that lasts for tens of seconds following a burst of presynaptic activity. It has been proposed that PTP arises from protein kinase C (PKC) phosphorylation of Munc18-1, an SM (Sec1/Munc-18 like) family protein that is essential for release. To test this model, we made a knockin mouse in which all Munc18-1 PKC phosphorylation sites were eliminated through serine-to-alanine point mutations (Munc18-1SA mice) and we studied mice of either sex. Expression of Munc18-1 was not altered in Munc18-1SA mice, and there were no obvious behavioral phenotypes. At the hippocampal CA3 to CA1 synapse, and the granule cell parallel fiber to Purkinje cell (PF to PC) synapse, basal transmission was largely normal except for small decreases in paired-pulse facilitation that are consistent with a slight elevation in release probability. Phorbol esters that mimic activation of PKC by diacylglycerol still increased synaptic transmission in Munc18-1SA mice. In Munc18...

Alzheimer’s disease (AD) is associated with poor sleep, but the impact of tau and β-amyloid (Aβ) pathology on sleep remains largely unknown. Here, we test the hypothesis that tau and Aβ predict unique impairments in objective and self-perceived human sleep under real-life, free-living conditions. Eighty-nine male and female cognitively healthy older adults received 18F-FTP-tau and 11C-PIB-Aβ PET imaging, 7 nights of sleep actigraphy and questionnaire measures, and neurocognitive assessment. Tau burden, but not Aβ, was associated with markedly worse objective sleep. In contrast, Aβ and tau were associated with worse self-reported sleep quality. Of clinical relevance, Aβ burden predicted a unique perceptual mismatch between objective and subject sleep evaluation, with individuals under-estimating their sleep. The magnitude of this mismatch was further predicted by worse executive function. Thus, early-stage tau and Aβ deposition are linked with distinct phenotypes of real-world sleep impairment, one that inc...

Alzheimer’s disease (AD) is a progressive neurodegenerative disease marked by the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles. Aβ oligomers cause synaptic dysfunction early in AD by enhancing long-term depression (LTD, a paradigm for forgetfulness) via metabotropic glutamate receptor (mGluR)-dependent regulation of striatal enriched tyrosine phosphatase (STEP61). Reelin is a neuromodulator that signals through ApoE receptors to protect the synapse against Aβ toxicity (Durakoglugil et al., 2009) Reelin signaling is impaired by ApoE4, the most important genetic risk factor for AD, and Aβ-oligomers activate metabotropic glutamate receptors (Renner et al., 2010). We therefore asked whether Reelin might also affect mGluR-LTD. To this end, we induced chemical mGluR-LTD using DHPG (Dihydroxyphenylglycine), a selective mGluR5 agonist. We found that exogenous Reelin reduces the DHPG-induced increase in STEP61, prevents the dephosphorylation of GluA2 and concomitantly blocks mGluR-mediated LTD...

Hyperphosphorylation of the microtubule associated protein tau (tau) is inextricably linked to several neurodegenerative diseases, collectively termed tauopathies, in which synapse dysfunction occurs through largely unidentified mechanisms. Our research aimed to uncover molecular mechanisms by which phosphorylation of tau (pTau) affects synapse function. Using combined molecular and electrophysiological analysis with in vitro genetic knock-in of phosphorylation mutant human tau in male rat CA1 hippocampal neurons, we show an interplay between tau and protein kinase C and casein kinase substrate in neurons protein 1 (PACSIN1) that regulates synapse function. pTau at serine residues 396/404 decreases tau:PACSIN1 binding and evokes PACSIN1-dependent functional and structural synapse weakening. Knockdown of tau or PACSIN1 increases AMPA receptor-mediated current at extrasynaptic regions, supporting a role for these proteins in affecting AMPA receptor trafficking. The pTau-induced PACSIN1 dissociation may repre...

Maintaining and manipulating sequences online is essential for daily activities such as scheduling a day. In Parkinson's disease (PD), sequential working memory deficits have been associated with altered regional activation and functional connectivity in the basal ganglia. This study demonstrates that the substantia nigra (SN) integrity correlated with basal ganglia function and sequencing performance in 29 patients with PD (17 women) and 29 healthy controls (HCs; 18 women). In neuromelanin-sensitive structural magnetic resonance imaging (MRI), PD patients showed smaller SNs than HCs. In a digit-ordering task with functional MRI (fMRI), participants either recalled sequential digits in the original order (pure recall) or rearranged the digits and recalled the new sequence (reorder and recall). PD patients performed less accurately than HCs, accompanied by the caudate and pallidal hypoactivation, subthalamic hyperactivation, and weakened functional connectivity between the bilateral SN and all three basal g...

Gain-control mechanisms adjust neuronal responses to accommodate the wide range of stimulus conditions in the natural environment. Contrast gain control and extraclassical surround suppression are two manifestations of gain control that govern the responses of neurons in the early visual system. Understanding how these two forms of gain control interact has important implications for the detection and discrimination of stimuli across a range of contrast conditions. Here, we report that stimulus contrast affects spatial integration in the lateral geniculate nucleus of alert macaque monkeys (male and female), whereby neurons exhibit a reduction in the strength of extraclassical surround suppression and an expansion in the preferred stimulus size with low-contrast stimuli compared with high-contrast stimuli. Effects were greater for magnocellular neurons than for parvocellular neurons, indicating stream-specific interactions between stimulus contrast and stimulus size. Within the magnocellular pathway, contra...

Two forms of information, frequency (content) and ordinal position (structure), have to be stored when retaining a sequence of auditory tones in working memory (WM). However, the neural representations and coding characteristics of content and structure, particularly during WM maintenance, remain elusive. Here, in two EEG studies in human participants (both sexes), by transiently perturbing the “activity-silent” WM retention state and decoding the reactivated WM information, we demonstrate that content and structure are stored in a dissociative manner with distinct characteristics throughout WM process. First, each tone in the sequence is associated with two codes in parallel, characterizing its frequency and ordinal position, respectively. Second, during retention, a structural retrocue successfully reactivates structure but not content, whereas a following white noise triggers content but not structure. Third, structure representation remains stable, whereas content code undergoes a dynamic transformatio...

Neuroimmune interaction during development is strongly implicated in the pathogenesis of neurodevelopmental disorders, but the mechanisms that cause neuronal circuit dysregulation are not well understood. We performed in vivo imaging of the developing retinotectal system in the larval zebrafish to characterize the effects of immune system activation on refinement of an archetypal sensory processing circuit. Acute inflammatory insult induced hyperdynamic remodeling of developing retinal axons in larval fish and increased axon arbor elaboration over days. Using calcium imaging in GCaMP6s transgenic fish, we showed that these morphologic changes were accompanied by a shift toward decreased visual acuity in tectal cells. This finding was supported by poorer performance in a visually guided behavioral task. We further found that the pro-inflammatory cytokine, interleukin-1β (IL-1β), is upregulated by the inflammatory insult, and that downregulation of IL-1β abrogated the effects of inflammation on axonal dynami...